Currently, metasurfaces (MSs) integrating with different active materials have been widely explored to actively manipulate the resonance intensity of multi-band electromagnetic induced transparency (EIT) windows. Unfortunately, these hybrid MSs can only realize the global control of multi-EIT windows rather than selective control. Here, a graphene-functionalized complementary terahertz MS, composed of a dipole slot and two graphene-integrated quadrupole slots with different sizes, is proposed to execute selective and active control of dual-band electromagnetic induced reflection (EIR) windows. In this structure, dual-band EIR windows arise from the destructive interference caused by the near field coupling between the bright dipole slot and dark quadrupole slot. By embedding graphene ribbons beneath two quadrupole slots, the resonance intensity of two windows can be selectively and actively modulated by adjusting Fermi energy of the corresponding graphene ribbons via electrostatic doping. The theoretical model and field distributions demonstrate that the active tuning behavior can be ascribed to the change in the damper factor of the corresponding dark mode. In addition, the active control of the group delay is further investigated to develop compact slow light devices. Therefore, the selective and active control scheme introduced here can offer new opportunities and platforms for designing multifunctional terahertz devices. Over the last few decades, the electromagnetic induced transparency (EIT) first observed in the atomic system has aroused a lot of interest because it allows the enhancement of transmission within a narrow frequency range along with strong dispersion properties and displays promising engineering prospects ,2,3. How2-integrated MSs [To overcome the above limitation, a variety of THz MSs with multi-band EIT windows were designed to actively modulate resonance properties by means of different approaches, including mechanical movement, phase change material, and graphene. For example, Devi et al. designed a concentrically coupled asymmetric THz MS to obtain a dual-band EIT effect; moreover, the dual-band EIT effect can be effectively modulated by rotating the element angle or by changing the asymmetric degree of the unit cell . Chen etated MSs . In addiated MSs ,14, teraated MSs ,16, and ated MSs  devices.ated MSs . Meanwhiated MSs ,20. Amonated MSs ,22,23.Here, we propose a scheme to obtain a dual-band EIR window in a graphene-functionalized complementary THz MS consisting of two dolmen-like slot structures with different sizes and two graphene ribbons connecting to different top gates. The basic article structure is as follows: First, the structural design and parameter selection of the proposed MS are described in detail, as well as the simulation setting. Second, the formation process and the physical mechanism of two EIR windows are elucidated through the analysis of different element arrays in a unit cell and field distributions. Then, the selective and active control of two EIR windows are further investigated by tailoring the Fermi energy of the corresponding graphene ribbons via electrostatic doping. Moreover, the field distributions and classic three-oscillator model are employed to discover the selective and active control mechanism of two EIR windows. Finally, the active control of the group delay originating from strong phase dispersion is also investigated to develop compact slow light devices. Therefore, the results obtained for our devices could provide new opportunities and platforms for the design and development of multi-function terahertz devices.7 S/m was employed as the slot resonators during the calculation [2 film with a permittivity of 3.9 and thickness of 30 μm were used as the substrate and dielectric layer, respectively. Since the graphene is composed of a one atom-thick layer of carbon atoms arranged in a hexagonal pattern, generally, the graphene is assumed to be a 1.0-nm-thick homogenous layer in order to facilitate simulation [To investigate the THz response of the proposed complementary MS, numerical calculations were conducted using the FDTD method, in which the boundary conditions in the x- and y-directions were set as the unit cell, and the z-direction was left open. The x-polarized incident light was normally illuminated on the surface of the designed complementary MS along the z-direction, as displayed in culation , while tmulation , while tmulation :(1)εg=1+ω is the angular frequency, tg is the single-layer graphene thickness, and ε0 is the vacuum permittivity. In the terahertz range, the graphene conductivity σg is described by the following expression [e is the electron charge, Bk is the Boltzmann’s constant, T is the Kelvin temperature, and FE is the Fermi energy of graphene. τ is the carrier relaxation time described by T = 300 K, Here, pression :(2)σ=−jeulations . Accordiulations , and theεr and ds are the relative permittivity and thickness of the SiO2 dielectric layer. Thus, by tuning the conductivity of graphene through the gate voltage gV, the THz properties of the designed device could be effectively controlled.Here, x-polarized incident wave, as presented in x-polarized incident wave, which serves as a bright mode, as shown by the shallow blue line in To disclose the formation process of dual-band EIR effect, first, the reflection spectra of four different complementary MSs, consisting of a longer quadrupole slot array alone, a dipole slot array alone, and shorter quadrupole slot array alone as well as their combined structure were calculated for the x-direction, and the corresponding field distributions at three different resonance frequencies, marked as the symbols “A”, “B”, and “C” in To further understand the physical mechanism of the two EIR windows, the field distributions of the designed structure were calculated when the incident wave was polarized along the f1 andEf2, respectively. Thus, by independently tuning any of Ef1 and Ef2 or by synchronously tuning Ef1 and Ef2, the graphene-functionalized MS can execute three different ways to control the resonance intensity of the two windows, as shown in f1 is individually tailored and when Ef2 is maintained at 0.1 eV. It can be clearly observed that when Ef1 increases from 0.1 eV to 0.5 eV, the intensity of Window I changes dramatically, while Window II remains unchanged. For example, as Ef1 increases from 0.1 eV to 0.4 eV, the amplitude of Window I decreases from 76% to 56%. With further increases to 0.5 eV, however, Window I is totally switched off and becomes a broad resonance valley. The extinction of Window I can be attributed to the increasing conductivity of the graphene. Thus, Window I can be independently controlled by merely tuning Ef1. To individually tune Ef2 from 0.1 eV to 0.5 eV, a similar change is also observed in Window II, with dependent control of Window II being obtained by Window I shifting Ef2 on its own, as shown in f1 and Ef2, however, is shown in f1 and Ef2 increase, the two windows weaken gradually and are annihilated, eventually becoming a considerable broad resonance dip, different from that of f1 and Ef2. In addition, it is noteworthy that during the entire modulation process, the locations of the two windows remain almost unchanged. To evaluate the modulation effect of the three control methods discussed above, the intensity modulation depth of the two windows is calculated by ΔR/R0 = (R0 − Rg)/R0, where R0 and Rg are the reflectance amplitude of the window without and with graphene, respectively. Thus, the corresponding intensity modulation depths are 46% when shifting Ef1 alone, 46% when shifting Ef2 alone, and more than 40% when simultaneously shifting Ef1 and Ef2. Therefore, the two windows can be selectively and actively modulated by tuning the Fermi energy of the corresponding graphene ribbons. Based on this scheme, a MSs with more windows can also be realized, in which each EIR window can be independently and actively controlled.To examine the selective and active modulation of the two windows, we next investigated the tunable characteristics of the graphene-functionalized MS by tailoring the Fermi energies of two graphene ribbons, in which the Fermi energy of the graphene ribbons beneath the long and short quadrupole slots are denoted by Ef1 and Ef2 values obtained by simultaneously doping two graphene ribbons. At Ef1 = 0.10 eV and Ef2 = 0.08 eV, the graphene ribbon can be regarded as a semiconductor with low conductivity, and the confined magnetic and electric fields are strongly focused on the corresponding quadrupole slots , , and  are the resonance intensities and damping factors of three oscillators a, b, and c, respectively. ωa, bω, and cω are the resonance frequencies of the three resonators before coupling. abκ denotes the coupling coefficient between resonator b and oscillator a, while bcκ is the coupling coefficient between resonator b and oscillator c. q represents the coupling coefficient between resonator b and the incident wave. After solving Equations (4)–(6), the energy dissipation of the graphene-functionalized complementary MS as the functions of the frequency is given as follows:j = ωjC2 + jiωγ − ω2 . According to Equation (7), the simulated reflection spectrum can be theoretically fitted, and the corresponding fitting results are shown in To discover tunable mechanism, a classic three-oscillator coupled model was employed to describe the designed graphene-functionalized MS composed of a dipole slot and two graphene-integrated quadrupole slots. In this model, the dipole slot is denoted by the oscillator  follows : (4)x¨a [f1 and Ef2. As expected, there is a notable phase dispersion around two EIR windows; moreover, the dispersion in phase shift progressively weakens with Ef1 and Ef2. f1 and Ef2 are 0.30 eV and 0.27 eV, respectively, the two group delays are suppressed to 0.36 ps and 0.32 ps, owing to the phase dispersion being weakened. As Ef1 and Ef2 are further increased up to 0.60 eV and 1.0 eV, the group delay totally disappears and becomes a negative value. Moreover, the selective control of the two delay groups can be also observed by doping the corresponding graphene ribbon (not shown here). By doping the corresponding graphene ribbon, the graphene-functionalized MS can also achieve the ability to selectively control the group delay, which has potential applications for the development of compact slow light devices.As it is widely known, one remarkable feature of the EIT effect is that it is accompanied by strong phase dispersion slowing down the light speed, thus exploiting slow light devices. Generally, slow light effect can be quantitatively characterized by a group delay (equency) , as showIn conclusion, we have numerically demonstrated the selective and active control of two EIR windows in a graphene-functionalized complementary MS consisting of a dipole slot and two graphene-integrated quadrupole slots of different sizes. In the structure, two EIR windows are induced by destructive interference originating from near field coupling between the dipole and the quadrupole slots and can be selectively or synchronously modulated by doping the corresponding graphene ribbons. The theoretical model and field distributions discovered that such active control can be ascribed to the increased damping factor of the dark element. In addition, the group delay is also actively controlled by doping the corresponding graphene ribbons, which is well-suited for the development and application of compact slow light devices. Based on this scheme, the selective and active control of multiple windows can further extend to other functionalized MSs by implanting different dark elements integrated with active materials, which offer new opportunities and platforms for the design of multifunctional terahertz devices.


With the development of material science, micro-nano-fabrication and microelectronics, the higher level requirements are posed on the electronic skins (E-skin). The lower energy consumption and multiple functions are the imperative requirements to spurred scientists and mechanists to make joint efforts to meet. To achieve lower energy consumption, a promising energy-harvesting style of triboelectric nanogenerators (TENG) is incorporated into the field effect transistors (FETs) to play the important role for sensor. For bifunctional sensor, to harness the difficult for reflecting the magnitude of frequency, we resorted to synaptic transistors to achieve more intelligentization. Furthermore, with regards to the configuration of FET, we continued previous work: using the electrolyte gate dielectrics of FET—ion gel as the electrification layer to achieve high efficient, compact and extensively adoption for mechanosensation. The working principle of the GFET was based on the coupling effects of the FET and the TENG. This newly emerged self-powered sensor would offer a new platform for lower power consumption sensor for human–machine interface and intelligent robot. The developments of material science, microelectronics, and integrated circuits have prompted the strong push towards flexible electronics dramatically4, achieving breakthrough in high sensitivity, responsiveness, high stretch ability, integration and intelligentialization. To suppress energy consumption, self-powered sensor has become a hot-pot, driving extensive attentions practically and academically. Triboelectrical nanogenerators (TENG), as an economical and high-efficient way to convert mechanical energy into electricity through coupling of tribo-electrification and electrostatic induction, have been driven extensive interests10. The TENG-based self-powered flexible electronic sensors have offer facile platform for monitoring temperature, humidity, physiological activity and other physical parameters14. To achieve high precision and high level of integration, the triboelectric potential originated form TENG can be incorporated into the field effect transistors (FETs) to tailor the transport properties of semiconductor channel for a myriad of versatile self-powered tribotronic devices17.The tribotronic devices have widespread applications in phototransistor, logic device, memristor, phototransistor, photovoltaic device and so on20.Electronic skins (E-skin)21. Apart from energy-efficiency, emulating the human’s skin of perception multiple stimuli is also an important issue to be addressed. For example, Sun et al.22 incorporated humidity sensor of GO, temperature of rGO into the pressure sensor (graphene electrode as electrode) to realize triple sensor for humidity, temperature and pressure. It is well-known that skin can percept both high frequent and lower frequent stimuli23. However, it was difficult to detect magnitude of frequency of the high frequent stimuli intuitively. To harness this problem, we resorted to plasticity behaviour synaptic transistor (transistor served both synaptic transistor and sensing unit). In synaptic transistor, synaptic weight (the increment phenomenon of later post-synaptic current compared with former counterpart) varied with the variation of frequency of pre-synaptic stimuli 24. In our work, we assigned wind as stimuli source , the increment of post-synaptic current of No. n pulse compared with No. n-1 pulse was explored to indicate the real-time frequency of wind that the sensor experienced. The mechanism involved triboelectric and electrostatic inducing. The work principal of magnetic field sensor was that (magnetic film and ion gel as friction layer) the magnetic field changed the distance between magnetic film and ion gel, giving rise to different signal. 21.Our previous work presented a noncontact mechanosensation active matrix based on tribotronic planar graphene transistors array to low-energy-cost real-time sensor and 2D imaging25. Furthermore, graphene was selected as channel semiconductor for high mobility  graphene with mobility approaching 200,000 cm2 V−1 s−1 for the carrier density below 5 × 109 cm−2 at a low temperature26), high transparency (the white light absorbance of a suspended graphene monolayer is 2.3% (or transmittance of 97.7%) with a negligible reflectance of < 0.1%27), excellent thermal stability and conductivity (3000–5000 W m−1 K−1)28, high Young’s modulus (~ 1 TPa)29 and large theoretical specific surface area 30. Owing to these particular merits, graphene field effect transistor (GFET) applied as synaptic has reports31.Incorporating synaptic transistors into E-skin has already been studied. Ravinder reported a printed synaptic transistor to create E-skin with positive mind and opened up a novel reformation: inserting Neuro layer into E-skin, possessing own Neuro and can immediately respond to external stimuli in absence of instruction. This project would invoke the reformation of wearable technology, flexible electronic and new generation computerTo summarize, we, developed a self-powered dual mode sensor for monitoring wind stimuli and magnetic stimuli, respectively. The wind stimuli represent the high frequency stimuli. One of the high frequent stimuli in daily life is physiotherapy instrument which acts quickly on the human body. We detected magnetic signals due to that magnetic fields or information related to magnetic fields exist in many places of our daily life. Particularly, we induced synaptic transistor into high frequency sensor to broad the horizon of the intelligentization of E-skin.32, electrons transfer from the Al to FEP, leaving net positive electrostatic charges on the surface of Al layer and negative charges on the FEP film. Here, the charges with opposite polarities are totally balanced. Upon the wind flowing, the negatively charged FEP layer separates from the Al, the surplus positive charges on the Al film attract electrons of Au gate electrode of FET and change the charge distribution of the surface of ion gel, inducing an EDL at the interface between Au gate electrode of FET and ion gel, ion gel and graphene, leaving anions at ion-gel/graphene interface, which is amount to applying a negative voltage on the GFET. Consequently, the Fermi level of graphene channel is shifted downwards and the charge injection barrier between source electrode and graphene channel decreases, leading to an increment in the output current.Figure −1 (G band) and at ~ 2694 cm−1 (2D band). The full width at half-maximum (~ 29 cm−1) of symmetric 2D band and the 2D/G intensity ratio (~ 2.5) are the solid evidences for testifying the monolayer graphene. Specially, G-band of graphene undergoes a blue shift from 1578 cm−1 to 1597 cm−1 suggests a slight p-type doping of graphene by moisture and oxygen31. With regards to intuitively reflect frequency of stimuli via synaptic plasticity of GFET, the stable and reversible triboelectric properties of GFET were essential. For desirable triboelectric properties, the stable electrical properties were the prerequisite.Figure ID) increases from 51 μA to 308 μA with gate voltage (VG) increasing from 0 to 2 V at a drain voltage (VD) of 0.5 V. Figure ID increases with VG increment in both positive and negative directions, indicating ambipolar charge transport property of graphene. The GFET can operate at a low gate voltage (< 2 V) due to the ultrahigh capacitance of the ion gel gate dielectric (6 ~ 7 μF cm−2). Figure VD, the absolute value of ID increased (51 μA to 67.1 μA) as the distance between FEP film and Al film of TENG increases from 0 to 600 µm, which is equivalent to applying increased gate voltage in negative direction. With respect to corresponding tribotronic transfer curve (at a given VD of 0.1 V), when the contact distance increased from 0 to 1 mm, the absolute value of ID increases from 20.1 μA to 32.99 μA, which is equivalent to applying a gate voltage of 0.15 V. Initially, the FEP film and Al film are in full contact with each other, resulting in a charge neutralization state. On basis of the triboelectric series32, electrons transfer from the Al film to FEP film, leaving positive charges on the surface of Al film and negative charges on the surface of FEP film. By now, the charges with opposite polarities achieve complete equilibrium and the Fermi level of graphene not changes. Upon the negatively charged FEP film vertically separates from the Al at a distance away, positive charges on the surface of Al attracted the electronic of Au electrode and produced surplus positive charge on surface of Au electrode. Consequently, induced EDL is produced within ion gel, leaving negative ions at ion-gel/graphene interface, which is amount to applying a negative pulse voltage on the semiconductor channel. Therefore, the Fermi level of graphene channel is shifted downwards, giving rise to an increment of the output current. To elucidate the dynamic tribotronic performance through external TENG, real-time triboelectrical tests were performed, as shown in Fig. ID was stable, verifying the reliability of triboelectric-driving GFET for synaptic device.Figure ID decreases (64.6 μA to 51 μA) as the magnitude of magnet field intensity increases from 7 mT to 14.6 mT, equivalent to applying increased gate voltage in positive direction. With respect to corresponding tribotronic transfer curve (at a given VD of 0.1 V), when the magnitude of magnet field intensity increases from 7 mT to 14.6 mT, the ID decreases from 25.1 μA to 20.1 μA. The variation rate was 0.66 µA mT−1 (As the magnitude of magnet field greater than 7 mT). It is mentioned that due to overcoming the weight of magnetic film, only the magnet field greater than 7 mT can drive the magnetic film separated from ion gel. . As a results, the functional relationship of ID and magnitude of magnet field is ID = I0 − 2.69% I0 (H-7) , I0 is assigned to the initial value of drain current. As the ion gel is intrinsically ion liquid gelation with the cross-linked polymer, its coupling with triboelectric field in different directions will lead to the distribution of electric double layers (EDLs) in opposite directions. According to the triboelectric series32, the triboelectric series ion gel can be utilized as a neutral friction material. . Compared with ion gel, PDMS is a negative triboelectric material. In absence of magnetic field, positive charges and negative charges are left on the surface of ion gel and PDMS, respectively, originating from the tribo-electrification and electrostatic induction between ion gel and PDMS. Owing to equivalent positive charge and negative charge were inter-neutralization, there is no change in ion gel and graphene. As magnet approach nearly to magnet film, due to attract interaction, the negatively charged magnet film leave away from ion gel, the anions in ion gel are attracted to compensate the accumulated positive charges, while the cations migrate to the ion-gel/graphene interface and the Fermi level of graphene is up-sifted. On the contrary, when the magnet leaves away from the magnet film, the negatively charged magnet conformally adhered the ion gel again, the positive charge on the surface of the ion gel and negative charge on surface of the magnet film were inter-neutralization again and there is no EDL on ion-gel/graphene interface and Fermi level of graphene restored. Furthermore, the magnitude of magnetic field has closely related to the distance of contact-and-separation between magnetic film and ion gel and determines the triboelectric potential posed on GFET, further posing impact on output current of GFET.The magnetic field stimuli behaviors were also investigated  magnitude when the input spikes stimulate the synapse. The ability of controlling and retaining the synaptic weight over time is defined as synaptic plasticity, classifying into two forms: short-term plasticity (STP) and long-term plasticity37. Figure pre = 60 ms, spike duration time = 100 ms). Owing to PPF (= (A1 − A2)/A1 × 100%) as a function of the time interval when two sequential spikes generate PSC peaks, Fig. pre curve values exponentially decay as the interval increases, and this decay characteristic showed the best agreement with the fitting function with two decaying time constants of C1exp (− Δt1/τ1) + C2exp(− Δt2/τ2). Using C1 and C2 as fitting parameters, we obtained two decaying time constants,τ1 = 16 ms and τ2 = 2741 ms. This PPF behavior is similar to the reported one in biological synapses, indicating our synaptic transistor can functionally mimic the biological synapse. As analogous to single pulse, the dual and multiple was also heavily related to the magnitude of stimuli intensity and tension time. Variation frequency of dual-spike pulse wind serve as triboelectric pulse (4 Hz–16 Hz), the EPSC was measured  feature of a synapse, providing flexibility for several neuronal tasks, such as simple learning and information processing in the frequency domain2/A1 is showed in Fig. N/A1 as the frequency at 5 Hz and is shown in Figure. The frequency dependent synaptic was also studied using 10 pulses with different frequencies (5 Hz–12.5 Hz) and the EPSC was measured Fig. a. The co39, when the pulse interval is shorter than relaxation time of ions within ion gel, some of these trapped ions are reluctant to return to their equilibrium positions before the second spike initiated. Consequently, these residual ions induce additional charges in the channel, leading to an increase in channel current and PPF behavior. When the FEP separates from Al again, positive charges on the surface of Al attract the electrons of Au electrode, giving rise to surplus positive charge on surface of Au electrode and producing EDL within ion gel. This newly emerged EDL pluses the remanent regular-aligned charges at ion-gel/grapheme interface during the first pulse process, increasing negative ions at ion-gel/graphene interface, which explained for that increment of second ESPC compared to ESPC of first pulse (PPF behavior). Furthermore, the magnitude of the PPF has closely related to the pulse interval. Large pulse interval allowed these mobile ions to relax back to their equilibrium positions prior to the second spike application leading to weak channel current modulation and lower PPF index.Figure ID decreases from 25.1 µA to 20.1 µA (VD = 0.1 V), with the variation rate 0.66 µA mT−1. The every 1mT magnitude of magnetic field intensity induces current varied 2.63% .The extracted functional relationship of ID and magnitude of magnet field is ID = I0 − 2.63% I0 (H-7). So, the calculated magnitudes of magnetic field intensity are 7.53 mT, 7.81 mT and 7.90 mT. Therefore, this sensor shows promising applications for intuitively monitoring frequency by means of synaptic transistor, as well as sensing the magnitude of magnetic field intensity to realize dual sensing.On account of impractical of simultaneously controlling multiple units for magnetic field, we implemented only one transistor to sensor. Further work will conduct for the active matrix E-skin for multiple-functional sensor needs. If wind stimuli and magnetic stimuli conduct simultaneously, two signals will overlap and it is difficult to distinct between them. So wind and magnetic stimuli were carried out successively. As shown in Fig. As a summarization, to emulate the multiple stimuli-responsiveness of skin, this work explored high- frequent stimuli wind and low-frequent stimuli magnet bifunctional responsiveness of the GFET sensor. Particularly, we proposed a strategic method to overcome the obstacle of reflecting the magnitude of frequency of high-frequent stimuli in transitional E-skin. Inspired by PPF phenomenon (the increment behavior of No. n pulse compared with No.n-1 pulse) of synaptic transistor, we achieved indicating the frequency of high-frequency wind stimuli with perceptual intuition by measurement of synaptic weight of the EPSC (referred to No. n pulse compared with No.n-1 pulse). The mechanism involved triboelectric and electrostatic inducing. The wind stimuli is by means of wind driving friction of electrofrictional layer of TENG. The work principal of magnetic field sensor is that (magnetic film and ion gel as friction layer) the magnetic field changes the distance between magnetic film and ion gel and produces to different signals. We ingeniously incorporated synaptic transistor into E-skin, opening a new avenue for intelligentization of E-skin.High quality mono-layer graphene films were prepared on a Cu foil  via CVD process:2SO4 and 30 wt% H2O2 for 15 min. Subsequently, Cu foil was rinsed with DI water and dried under a nitrogen flow. Inserting the Cu foil into a quartz tube was prior to pumping air in the chamber. Upon the pressure in the quartz tube reaching 5 × 10-3 Torr, the Cu foil was annealed at 1000 °C for 30 min, under a continuous flowing H2 (10 sccm) atmosphere. 5 sccm CH4 was then introduced for graphene growth. After 30 min, the CH4 flow was ceased, while the H2 flow was continued to apply until the tube was cooled to room temperature. Thus, large area (10 × 10 cm2) mono-layer graphene was obtained on a Cu foil41.Initially, a Cu foil (25 μm) was cleaned with a mixture solution containing 98wt% HPDMS and curing agent mixed according to the ratio of 10:1, adding to 5–10 wt% magnetic powder (size 500 nm–2 μm), fully mixed and pouring on glass slide (which pre- treated using trichlorosilicane), spining coating at 500–800 rpm for 1 min. Cured 2 h at 80 °C and peeled off the film from the glass slide.−1); the floated monolayer graphene films was then transferred onto the PET substrate; the supporting PMMA layer was removed by dipping into the hot acetone (~ 60 °C ) for 5 min. Graphene was then patterned by standard photolithography  and subsequent oxygen plasma etching  process. Residual photoresist was removed with acetone. The ion gel paste-shape liquid composed of the 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]) ion liquid, the poly(ethylene glycol) diacrylate (PEGDA) monomer, and the 2-hydroxy-2methylpropiophenone (HOMPP) photo-initiator (weight ratio of 90:7:3) was dipped onto the patterned graphene. Under UV exposure, polymerization of PEGDA was initiated by the reaction between monomers and radicals originated from HOMPP to produce cross-linked structure. The unexposed region was washed away using DI water. The graphene region in contact with the ion gel served as the active channel, whereas the other region functioned as the source/drain electrodes43.PET substrate (120 μm) was cleaned under sonication with acetone, isopropanol and DI water, respectively. Transfer graphene included the following steps: oxygen plasma etching  of the graphene layers on the backside of Cu foil; poly(methyl methacrylate) (PMMA) supporting layer was spin-coated at 4000 rpms for 5 s onto the graphene patterns on the Cu foil; the Cu foil was electrochemically etched using an ammonium persulfate aqueous solution  and Al film. Al film connected to gate electrode of FET.21.UV–Vis measurements were carried out with an ultraviolet spectrophotometer (HOPBA). The electrical and tribotronic performance of the GFETs were implemented with an Agilent B1500A Semiconductor Device analyzer. During the tribotronic performance test, a displacement motor driven by a computer controlled stepping motor was connected to a probe station. All measurements were conducted under ambient conditionSupplementary Information.


The interest in the lung microbiome and virome and their contribution to the pathogenesis, perpetuation and progression of idiopathic pulmonary fibrosis (IPF) has been increasing during the last decade. The utilization of high-throughput sequencing to detect microbial and/or viral genetic material in bronchoalveolar lavage fluid or lung tissue samples has amplified the ability to identify and quantify specific microbial and viral populations. In stable IPF, higher microbial burden is associated with worse prognosis but no specific microbe has been identified to contribute to this. Additionally, no causative relation has been established. Regarding viral infections, although in the past they have been associated with IPF, causation has not been proved. Although in the past the diagnosis of acute exacerbation of IPF (AE-IPF) was not considered in patients with overt infection, this was amended in the last few years and infection is considered a cause for exacerbation. Besides this, a higher microbial burden has been found in the lungs of patients with AE-IPF and an association with higher morbidity and mortality has been confirmed. In contrast, an association of AE-IPF with viral infection has not been established. Despite the progress during the last decade, a comprehensive knowledge of the microbiome and virome in IPF and their role in disease pathogenesis are yet elusive. Although association with disease severity, risk for progression and mortality has been established, causation has not been proven and the potential use as a biomarker or the benefits of antimicrobial therapeutic strategies are yet to be determined. Despite its constant exposure to the environment, the lower respiratory tract has been considered sterile for years. This notion was based on the inability of the traditional sampling and isolation methods, especially microbial cultures, to identify microbes resident in the lung . The utiIdiopathic pulmonary fibrosis (IPF) is a devastating interstitial pneumonia of unknown cause, characterized by the fibrotic distortion of normal lung architecture leading to gas exchange abnormalities and ultimately respiratory failure and death . It affeDisease pathogenesis is yet elusive; however, the current paradigm has shifted from an inflammation-mediated disease. Instead, aberrant wound healing as a response to unknown, repetitive, low immunogenicity-generating stimuli is considered as the triggering and preserving mechanism underlying the fibrotic process ,13. SmokRecently, the microbiome, the entirety of the symbiotic and pathogenic microorganisms that compose the microbial ecosystem that inhabits our body, has gained attention concerning its relation to the initiation, perpetuation and exacerbation of the fibrotic process in IPF ,14,15. TIn this review, we summarize the available evidence regarding the lung microbiome in IPF patients, the available data regarding its association with the pathogenesis and its role in the clinical course of the disease. A summary of the studies and their main results can be found in The lung is the largest human organ in direct contact to the environment. A total epithelial and airways area of 50–75 square meters is in constant exposure to ambient air, while the total volume of air that passes through the lungs is estimated to be 10,000 L/day. In addition to that, the lungs are exposed to micro-aspiration of oropharyngeal and gastric content. Therefore, it should be expected that the lower respiratory tract is exposed to and can be the home of a plethora of microbes and viruses. Despite this, the dogma that lungs are sterile has persisted for many years and it is only during the last 10–15 years that this has changed. It is now accepted that the lower respiratory system is home to abundant and diverse populations of microbiota ..18].Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria [Prevotella, Streptococcus and Veillonella [In healthy subjects, the lung bacterial burden is twofold to fourfold lower compared to the oropharyngeal, but of similar composition . In addibacteria ,22,23. Tllonella ,22,23. Illonella . The lacllonella . Interesllonella ,25. Intellonella .Unlike the microbiome, the lung virome has been less well studied. It is stated however that the virome exhibits considerable variation and can be is considered as a triggering factor for many lung diseases .Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa and Proteus mirabilis have been isolated in cultures from BALF of 8 out of 22 patients with IPF [Historically, due to the prevailing dogma that lungs are sterile, resident microbial populations have not seen the same attention as viral infections as possible triggers of disease. It is now known that the lungs are not sterile and that the IPF lung specifically exhibits a distinct microbial flora compared to the normal lung . Despitewith IPF . NotablyNeisseria, Actinobacteria and Streptococcus species, have been detected in IPF patients [Pneumocystis Jirovecii infection [Prevotellaceae, Streptococcaceae and Acidaminococcaceae, with no significant differences among patients and healthy controls [Since the commencement of the employment of culture-independent techniques for the detection of microbial 16s-rRNA, organisms normally present in the oropharynx as well as organisms unable to be identified by microbial cultures, including patients . Garzoninfection . The miccontrols .Prevotella, Veillonella and Cronobacter spp. More importantly, the presence of a specific Streptococcus or Staphylococcus species, as identified by their Operational Taxonomic Unit (OTU), was associated with faster disease progression, even after adjusting for confounding factors [The Correlating Outcomes with biochemical Markers to Estimate Time-progression in idiopathic pulmonary fibrosis (COMET) multicenter cohort study was an effort to identify unique microbial signatures and investigate their association with disease progression . The aut factors . However factors .Veillonella, Neisseria, Streptococcus and Haemophilus spp. was consistently associated with IPF. No significant differences were found in the BAL of healthy control subjects and patients with COPD. The authors hypothesized that, when taking into consideration the results of the COMET study, it is the increased bacterial burden and not specific populations that can predict disease progression and mortality [Molyneaux et al. published a large study in 2014 that included 65 patients with IPF, 27 healthy controls and 17 patients with Chronic Obstructive Pulmonary Disease (COPD) . The autortality ,31.Firmicutes was more prevalent in IPF, while in cHP Proteobacteria were more abundant. At genus level, cHP had higher Staphylococcus burden while in IPF Actinomyces and Veillonella load was increased [Most recently, a study compared the microbiome of patients with IPF to that of patients with chronic hypersensitivity pneumonitis (cHP). The results suggested that the bacterial load in cHP is higher than normal controls, however it is significantly lower compared to that of subjects with IPF . Moreovencreased .Streptococcaceae, Veillonellaceae, and Prevotellaceae families and a decrease in the phylum Proteobacteria were involved in the reduction of diversity and correlated with low FVC and decreased 6MWT distance, as well as increased serum surfactant protein D (SP-D) and LDH [Impaired lung microbiota diversity has also been implicated in the progression of IPF. In a study by Takahashi et al., increases in BALf of the  and LDH . The res and LDH . HoweverIn contrast to the utilization of BAL for the detection of bacterial populations in the IPF lung, Valenzi et al. used a different approach . This stUnlike microbial detection that required technologically advanced techniques, viral detection through serology presented a more accessible option. Viral infections have been long considered as a potential precipitating factor for the development of IPF in susceptible individuals. Vergnon et al. have studied the association of the human herpes viruses (HHVs) as early as in 1984 . In thisThe hepatitis C virus (HCV) has also been associated with IPF, although inconsistently. In one study, serum antibodies against HCV have been found in 28.8% of 66 IPF patients compared to 3.66% of 9464 age and gender-matched controls . In addiSimilar to the study by Valenzi et al. , a studyThe latest revision of the diagnostic criteria for the acute exacerbation of IPF (AE-IPF) added overt infection as potential trigger of AE-IPF . In the Proteobacteria, Campylobacter spp. and Stenotrophomona spp., while a significant decrease was found in Veillonella spp. and Campylobacter spp. The authors concluded that the microbial burden might have a causative role in the pathogenesis of AE-IPF [Regarding bacterial burden and its contribution to AE-IPF, Molyneaux et al. have utilized bronchoscopy with BAL and DNA extraction and found that patients with AE-IPF had up to four times higher bacterial load when compared to stable IPF patients . Additiof AE-IPF . Notablyf AE-IPF .Klebsiella pneumonia accounted for 26%, Mycobacteria tuberculosis for 21% and Acinetobacter baumannii for 10% of the total strains [More recently, Weng et al. examined the sputum cultures of 170 patients with AE-IPF . Gram-ne strains .Streptococcus pneumoniae has been found to induce exacerbation of fibrosis [Pre-clinical studies in mouse models have also been used to test the hypothesis that microbial infection can be responsible for disease exacerbation. fibrosis . Moreovefibrosis . These dViral infections by serologic studies have also been investigated concerning their association with the development and progression of IPF, as well as with acute exacerbations . In a stDespite the progress in the identification of the microbiome and its association with IPF, it is still unclear whether there is a causal relation or if the altered microbiome is the result of the disease.Infection is carrying significant morbidity and mortality in IPF patients and is a known cause of acute exacerbation of the disease . In patiDespite the above-mentioned relations, a causative effect of the host-immune interactions and the development of IPF has not been established yet. This potential association was studied by Molyneaux at al., who tried to explore the relation between the peripheral whole-blood transcriptome, the respiratory microbiome and the presence of MUC5B and TOLLIP polymorphisms in patients with IPF . More spStreptococcus sp. and poor PFS. Abundance of Staphylococcus and Prevotela sp. was also associated with worse PFS, decreased activation of immune defense pathways and overexpression of Toll-like receptor 9 (TLR-9) in peripheral blood mononuclear cells (PBMC) [Another study by Huang et al. attempted to explore the connection of microbial interaction and host immune response to the progression-free survival (PFS), in vitro fibroblasts function and leukocytes phenotypes . Sixty-es (PBMC) . The autA double-blind, randomized placebo-controlled trial by Varney et al., published in 2008, compared co-trimoxazole to placebo in patients with progressive fibrotic IIP . PatientIn a larger study, 181 patients with fibrotic IIP, mostly IPF, were assigned to either co-trimoxazole or placebo. After 12 months, co-trimoxazole had no effect on FVC, DLco, 6MWT or on dyspnea scores but improved quality of life markers and all-cause mortality on an intention-to-treat analysis . To furtAnother anti-microbial agent that has been studied in IPF is doxycycline. Mishra et al. recruited six patients with IPF in an open-label, prospective study to test the efficacy of long-term doxycycline as an inhibitor of metalloproteinases (MMPs). BALF samples were acquired before the initiation of doxycycline and while under treatment and MMPs levels were compared to those of healthy subjects . AdditioIn addition to the data above, the association of the microbiome to disease progression and to the immune system dysregulation in IPF, has led to the hypothesis that treatment with antibiotics could modulate the underlying microbiome of patients with IPF towards that of the normal lung ,46,59,60Bacteroidetes and Firmicutes, however there are differences at species level [The comparison of the lung microbiome with that of other systems has been extensively studied and the association with lung diseases such as asthma, COPD and lower respiratory tract infections (LRTIs) is known . The gases level ,68.The disruption of gut microbiome is known to precipitate diseases of the gastrointestinal tract, but also of other systems . The croRegarding IPF, there is no evidence of a direct involvement of the gut microbiota in the pathogenesis and progression of the disease. However, taking into consideration the increased frequency of Gastro-esophageal reflux in IPF patients, indirect implication of the gut microbiota can be presumed ,77. AddiThe coronovirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronovirus 2 (SARS-CoV2-2) has infected millions of people and has caused millions of deaths during the last 20 months . The cliTwo studies have tried to address the issue of long-term fibrosis attributed to COVID-19. A study by Mandal et al., followed-up patients with persisting abnormalities on blood samples or chest-X-ray (CXR) 47–59 days after their discharge . Of the Another study by Myall et al., screened 837 patients that have been hospitalized with COVID-19 . In 35 pApart from the possibility to induce a fibrotic response in the lungs, COVID-19 can be potentially lethal for subjects who already suffer from fibrotic lung disease. It is possible that patients with IPF might exhibit an increase in hospitalization and adverse events due to COVID-19. Surprisingly, a study by Papiris et al., including 550 patients with IPF demonstrated that they had lower rate of SARS-CoV-2 infection compared to general population and additionally fewer hospitalizations due to other lower respiratory tract infection and deaths were reported . These rCollectively, these data suggest that to this day, there is no evidence that COVID-19 can cause an IPF like clinical disease characterized by relentless progression and additionally adds credibility to the notion that subjects with IPF should practice social distancing during the winter months.The last decade has seen the advancements in molecular sequencing techniques revolutionizing the detection of microbial populations in the lung. Furthermore, the current understanding of IPF pathogenesis is based on the assumption that aberrant would healing as a response to unknown, repetitive, low immunogenicity-generating stimuli is the triggering and preserving mechanism underlying the fibrotic process. The role of microbiome in IPF is not yet fully elucidated, however it is clear that infection is a strong inducer of morbidity and mortality in these patients. In light of this, it is possible that the microbiome contributes to the triggering and preservation of the epithelial damage. Further studies focusing on the investigation of a causal relationship, on identifying microbial biomarkers and on exploratory therapeutic approaches are needed.


In the middle of the COVID-19 pandemic, students at the University of California, Irvine, reimagined their peer-led, small-group, tutorial sessions into an online format. The virtual sessions improved student-reported understanding of physiological principles and reduced exam anxiety. Peer-led review remains a valuable resource in the era of virtual medical education. The COVID-19 pandemic disrupted many aspects of pre-clerkship medical education at the University of California Irvine, School of Medicine (UCISOM), including peer-led exam review sessions, a form of peer-assisted learning (PAL), for first-year medical students (MS1s). PAL has broad benefits in undergraduate medical curricula . With thIn the fall of 2020, MS1s at UCISOM attended virtual, peer-led and faculty-led review sessions to prepare for upcoming physiology block examinations. Peer-led sessions were taught by six MS2 tutors via a rotating Zoom™ breakout room format. MS1 students were divided into six breakout rooms while MS2 peer tutors rotated between rooms and reviewed faculty-approved exam-relevant physiology topics. Tutors spent 20 min in each breakout room and devoted a third of that time to answering MS1 questions. Faculty-led review sessions consisted of content review and practice questions in a large-group Zoom™ format.To explore whether the previously demonstrated benefits of PAL persist when transformed into a digital platform, we surveyed MS1 perceptions of the online peer-led review session compared to the faculty-led sessions. The survey was modified from the published PAL questionnaire , consistOverall, our findings suggest that peer-led review sessions remain an acceptable alternative to faculty-led review sessions in the era of virtual learning, with students preferring peer-led review in various categories. This is consistent with the theory of cognitive congruence as it applies to PAL, which speculates that narrowing the knowledge gap between student and educator enhances learning. Factors such as usage of similar language between educators and students, as well as educators’ understanding of which concepts are important or difficult for learners to grasp, contribute to better educational outcomes , 4. Our In our previous study, we had inferred that student preference for peer-led review may in part be due to the utilization of a small-group format as it facilitates more direct interaction with the tutors . Interes


A315T mouse model. Therefore, we consider Tideglusib as a promising drug candidate for ALS, being proposed to start a clinical trial phase II by the end of the year.Amyotrophic Lateral Sclerosis (ALS) is the most common degenerative motor neuron disease in adults. About 97% of ALS patients present TDP-43 aggregates with post-translational modifications, such as hyperphosphorylation, in the cytoplasm of affected cells. GSK-3β is one of the protein kinases involved in TDP-43 phosphorylation. Up-regulation of its expression and activity is reported on spinal cord and cortex tissues of ALS patients. Here, we propose the repurposing of Tideglusib, an in-house non-ATP competitive GSK-3β inhibitor that is currently in clinical trials for autism and myotonic dystrophy, as a promising therapeutic strategy for ALS. With this aim we have evaluated the efficacy of Tideglusib in different experimental ALS models both in vitro and in vivo. Moreover, we observed that GSK-3β activity is increased in lymphoblasts from sporadic ALS patients, with a simultaneous increase in TDP-43 phosphorylation and cytosolic TDP-43 accumulation. Treatment with Tideglusib decreased not only phospho-TDP-43 levels but also recovered its nuclear localization in ALS lymphoblasts and in a human TDP-43 neuroblastoma model. Additionally, we found that chronic oral treatment with Tideglusib is able to reduce the increased TDP-43 phosphorylation in the spinal cord of Prp-hTDP-43 Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive muscle paralysis due to motor neuron degeneration in the brainstem and spinal cord, causing premature death, mainly owing to respiratory failure. The etiopathogenesis of ALS is still unclear involving altered signaling pathways such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress, protein aggregation, and neuroinflammation. Until now, no effective therapy to prevent the development and progression of the disease exists. Moreover, the heterogeneity of the disease both at the genetic and clinical levels had made the search for effective treatments a difficult task.TARDBP gene [Despite the heterogeneity, about 97% of patients show cytoplasmic inclusions in motor neurons containing TDP-43, the protein product of DBP gene . This suDBP gene . TDP-43 postmortem spinal cords and frontal and temporal cortex of ALS patients [Glycogen synthase kinase 3β (GSK-3β) has been identified as one of the protein kinases implicated in TDP-43 phosphorylation . GSK-3β patients ,8,9,10. patients .Drosophila [All these findings are consistent with those reported in different cellular and animal models where GSK-3β inhibitors treatment increased cell viability and improved motor function. Particularly, TDP-43-positive stress granule formation, as well as C-terminal TDP-43 fragments, were reduced in the presence of a GSK-3β inhibitor in transfected cells . Additioosophila ,14,15 anosophila ,17,18,19All of these data, combined with the promising outcomes reported in clinical studies in ALS patients treated with Lithium , the firThe main goal of our work is aimed to prove that reduction of the abnormal phosphorylation of TDP-43 with small molecules, inhibitors of specific kinases, could help to recover the homeostasis of this nuclear protein. In that sense, GSK-3β inhibitors emerge as new drug candidates. Tideglusib, a small thiadiazolidindione (TDZD), is an in-house designed non-ATP competitive GSK-3β inhibitor that has shown neuroprotective, anti-inflammatory, and neurogenic properties in different neurodegenerative models ,22. FurtOn the basis of this background, we have studied the effects of Tideglusib on TDP-43 homeostasis in cellular models of ALS, including immortalized lymphocytes from sporadic ALS patients, as well as in a TDP-43 (A315T) transgenic mouse model. Our results show the efficacy of Tideglusib in the recovery of TDP-43 homeostasis  in ethacrynic acid-treated human neuroblastoma SH-S5Y5 cells and in lymphoblasts from sporadic ALS patients. Moreover, we found that chronic oral treatment with Tideglusib is able to reduce the increased TDP-43 phosphorylation in the spinal cord of TDP-43 (A315T) transgenic mice. Altogether, our data support the repurposing of Tideglusib as a promising therapy for ALS.Recently, we demonstrated that lymphoblasts derived from sporadic ALS patients recapitulate the main TDP-43 pathological features such as increased phosphorylation, truncation, and cytoplasmic accumulation . TherefopSer9GSK-3β together with higher levels of pTyr216GSK-3β  treatment . For theMoreover, Tideglusib was effective in preventing the EA-induced cytosolic TDP-43 accumulation, restoring the homeostasis of the main pathological hallmark of ALS and increasing TDP-43 nuclear localization c.The involvement of GSK-3β in a number of important signaling pathways including the oncogenic β-catenin pathway  raises dNext, we seek to evaluate whether Tideglusib chronic treatment could prevent the enhanced TDP-43 phosphorylation in vivo. To this end, we analyzed the phosphorylation status of TDP-43 in the spinal cord of Prp-hTDP-43 (A315T) transgenic mice, one of the first experimental model of ALS based in TDP-43 mutations . These mpostmortem spinal cords and frontal and temporal cortex of ALS patients [ALS is a fatal motor neuron degeneration disease that lacks an effective treatment, thus, there is a pressing need to search for new therapies. Although ALS pathogenesis has not been fully elucidated yet, it is known that post-translational alterations in TDP-43 protein are present in approximately 97% of ALS patients . Changespatients ,9,10.We report, here, our results of the treatment of control and sporadic ALS lymphoblasts with Tideglusib, an in-house designed non-ATP competitive GSK-3β inhibitor, that have shown good safety and tolerability in patients with different neurological diseases ,25,26,34Our data show that GSK-3β inhibition by Tideglusib was accompanied by a significant reduction of the enhanced phosphorylation of TDP-43 protein, observed in ALS lymphoblasts as compared with cells derived from control individuals. In addition, it was found that Tideglusib partially prevented the anomalous cytosolic TDP-43 accumulation in ALS lymphoblasts, thus, recovering TDP-43 homeostasis. These effects of Tideglusib are in accordance with previous work from this laboratory, showing concomitant alterations in TDP-43 phosphorylation and TDP-43 nuclear translocation in either FTLD-TDP and ALS derived lymphoblasts ,30,35. TDespite the fact that ALS-associated changes detected in peripheral cells from patients might not fully reflect those of motor neurons, we have evaluated the potential neuroprotective role of Tideglusib in a neuronal cell model of induced TDP-43 phosphorylation driven by ethacrynic acid, as well as the efficacy of chronic oral administration of Tideglusib in transgenic TDP-43 (A315T) mice, one of the first experimental models of ALS based on mutations in TDP-43 protein . TidegluConsidering the key role played by GSK-3β in important cellular pathways , it was In summary, the results herein presented show neuroprotective effects of Tideglusib both in vitro and in vivo as it restores TDP-43 homeostasis by reducing the aberrant phosphorylation of TDP-43, a consistent feature observed in the cytoplasmic aggregates in affected tissues of about 97% of ALS patients. Given that Tideglusib have shown good safety and tolerability in patients suffering from different neurological diseases, it is proposed that the repositioning of this in-house designed GSK-3β inhibitor could be a valid therapeutic strategy for the treatment of ALS and other TDP-43 proteinopathies. Only results from clinical trials in patients suffering sporadic ALS patients will confirm this therapeutic potential. Recently, a phase II clinical trial protocol has already been approved for this purpose, being expected to begin by the end of the year.All components for cell culture were obtained from Invitrogen . Antibodies used in this study were from Santa Cruz Biotechnologies, Heidelgerb, Germany or Proteintech, Manchester, UK and are listed in Peripheral blood samples were obtained after written informed consent of the patients or healthy individuals listed in v/v) fetal bovine serum (FBS) and maintained in a humidified 5% CO2 incubator at 37 °C. Fluid was routinely changed every two days by removing the medium above the settled cells and replacing it with an equal volume of fresh medium.All study protocols were approved by Doce de Octubre Hospital and the Spanish Council of Higher Research Institutional Review Board and are in accordance with National and European Union Guidelines. Establishment of lymphoblastoid cell lines was performed in our laboratory as previously described by infecting peripheral blood lymphocytes with the Epstein-Barr virus . Cells w2 and 95% air. On attaining semiconfluency, cells were pre-treated in the absence or in the presence of Tideglusib (5 µM) during 1 h before the addition of ethacrynic acid (40 µM). 24 h later, cultures were processed for cell viability assay. Cell viability was determined by the MTT assay, as previously described [Human neuroblastoma (SH-SY5Y) cells were purchased from the European Collection of Cell Cultures , and were propagated in Dulbecco’s Modified Eagle Medium containing L-glutamine (2 mM), 1% non-essential amino acids, 1% penicillin/streptomycin, and 10% fetal bovine serum under humidified 5% COescribed . Cell suTARDBP transgene amplification, containing A315T mutation, confirmed mice genotypes. Wild-type and transgenic mice were identified with ear punching codes and randomly allocated to the different treatment groups. Tideglusib was orally administered at 200 mg·kg−1·day−1 for 40 days (P105). All the mice were housed at 22 ± 1 °C with natural light/dark cycles (12 h). High fat jelly food , specific for TDP-43 transgenic mice [ad libitum.All the experimental procedures were performed in accordance with the regulations for the use of laboratory animals in the European Commission (2010/63/EU), and with the approval of the ethical committees of the Center of Biological Research (CIB-CSIC) and the regulatory institution (ref. PROEX 066/18). Mice were bred in our animal facilities from initial breeders purchased from Jackson Laboratories . Sixty-five-days-old male Prp-hTDP-43(A315T) transgenic mice and non-transgenic littermate siblings were used. As described previously , the preCells were collected by centrifugation, washed with PBS and total protein extracts were obtained by lysing them as previously described . Nuclear6 × mL−1) or SH-S5Y5 cells  were fixed for 30 min in 4% paraformaldehyde in PBS and blocked and permeabilized with 0.5% Triton X-100 in PBS–0.5% BSA for 60 min at room temperature. Lymphoblasts were attached to poly-L-lysine-coated coverslips using the Cytospin centrifuge at 700 rpm for 7 min. After being fixed, cells were incubated overnight with anti-TDP43 polyclonal antibody. After removing the primary antibody, cells were washed with PBS and incubated with Alexa Fluor 488-conjugated anti-rabbit antibody. For nuclear staining, the preparations were mounted on ProLong® Gold Antifade Reagent with DAPI (Thermo Fisher) allowing nuclear visualization. High-resolution images were acquired for ∼ 45 cells per group in n = 2 independent experiments using the LEICA TCS-SP5-AOBS confocal microscope system . Quantification of TDP-43 was performed using Image J software. Data is expressed as the ratio of the fluorescence intensity of cytosolic TDP-43 vs. the intensity of the fluorescence of the nuclear protein.Lymphoblasts  followed by the Fisher’s LSD test for multiple comparisons. A value of p < 0.05 was considered significant.Statistical analyses were performed with Graph Pad Prism 9. All the statistical data are presented as mean ±standard error of the mean (SEM). Normality was checked with the Shapiro–Wilk test. Parametric tests were, therefore, used in the statistical analysis. Statistical significance was estimated by Student’s


Noncommunicable diseases (NCDs) constitute a burden on public health. These are best controlled through self-management practices, such as self-information. Fostering patients’ access to health-related information through efficient and accessible channels, such as commercial voice assistants (VAs), may support the patients’ ability to make health-related decisions and manage their chronic conditions.This study aims to evaluate the reliability of the most common VAs  in responding to questions about management of the main NCD.We generated health-related questions based on frequently asked questions from health organization, government, medical nonprofit, and other recognized health-related websites about conditions associated with Alzheimer’s disease (AD), lung cancer (LCA), chronic obstructive pulmonary disease, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), and cerebrovascular accident (CVA). We then validated them with practicing medical specialists, selecting the 10 most frequent ones. Given the low average frequency of the AD-related questions, we excluded such questions. This resulted in a pool of 60 questions. We submitted the selected questions to VAs in a 3×3×6 fractional factorial design experiment with 3 developers , 3 modalities , and 6 diseases. We assessed the rate of error-free voice responses and classified the web sources based on previous research .Google showed the highest total response rate, followed by Amazon and Apple. Moreover, although Amazon and Apple showed a comparable response rate in both voice-and-display and voice-only modalities, Google showed a slightly higher response rate in voice only. The same pattern was observed for the rate of expert sources. When considering the response and expert source rate across diseases, we observed that although Google remained comparable, with a slight advantage for LCA and CKD, both Amazon and Apple showed the highest response rate for LCA. However, both Google and Apple showed most often expert sources for CVA, while Amazon did so for DM.Google showed the highest response rate and the highest rate of expert sources, leading to the conclusion that Google Assistant would be the most reliable tool in responding to questions about NCD management. However, the rate of expert sources differed across diseases. We urge health organizations to collaborate with Google, Amazon, and Apple to allow their VAs to consistently provide reliable answers to health-related questions on NCD management across the different diseases. Noncommunicable diseases (NCDs) constitute a significant burden on public health ,2 and arCommercial voice assistants (VAs) can be employed on both smartphones and smart speakers, which are increasingly present in our daily lives. In fact, in 2018, 76% and 45% of individuals in advanced and emerging economies, respectively, owned a smartphone , 19.1 miIn addition, VAs leverage speech-based interaction, which makes information lookup more efficient and accessible compared to classical methods . ThiPrevious research investigated VAs’ reliability and assessed their ability to provide patients with reliable responses to health-related questions. These included mental and physical health, interpersonal violence , sexual response rate and source type. Based on previous research, we control for the effect of developer  and interaction modality  [This study evaluates the ability of common Vas, such as Amazon Alexa, Apple Siri, and Google Assistant, to vocally respond to questions related to NCD management, based on expert web sources. In particular, we measure reliability through raction)  and compraction) . This coraction) , but patraction) . TherefoHence, we seek to answer the following research questions:Our experiment consisted of a quality assurance evaluation, where experimenters submitted validated questions to VAs and assessed (1) whether an error-free voice response was provided and (2) the category of the referenced web source.modality, software developer, and NCD. We set a 3×3×6 fractional design with 3 modalities , 3 developers , and 6 diseases . For the display-only modality, we solely included the developer Google. The dependent variables were the response rate  and the source type .We manipulated 3 independent variables: interaction response rate and source type. To assess the response rate, we computed the percentage of error-free speech-delivered responses. Specifically, a response was included if (1) the VA did not manifest an error, such as a system error , a natural language processing (NLP) error , or an intent error , and (2) the response was voice-delivered without prompting the user to access information by interacting with a display device. For instance, if a VA was to reply Here is what I found and show results on the screen, we considered this response as not provided. Note that we leverage the use of VA for accessible, hands-free health-related information provision. Thus, we intentionally considered only those responses that could benefit individuals who cannot interact with a display.To measure the reliability of the different VAs, we assessed the display-only condition, we calculated the response rate by including all responses provided in the form of a web search featured snippet. A featured snippet is a unique box presented above the list of Google’s search results, containing a text answer to a question-like search query . A snippet contains a title, a summary of the answer, and a link to the web source [In the b source . We chosexpert, commercial, crowdsourced, or not stated. government, heath nonprofit, commercial, crowdsourced, or not stated. If a web source was categorized as government and heath nonprofit (which they defined as expert sources), the response would gain a point and would otherwise get no points. Following this approach, we merged government and heath nonprofit categories into one that we called expert and considered such sources as reliable because they consistently assure good quality of information. Furthermore, we verified the reliability by exploring primary websites or by finding third-party sources of reliability evaluation .The source type was categorized based on the work of Alagha and Helbing  and BoydFollowing Kvedar et al , we aimeIsAlzheimer’s disease genetic? on nia.nih.gov and Is lung cancer genetic? on foxchase.org, we searched for equivalents  or arbitrarily created one for other diseases . This process allowed us to obtain a more comprehensive pool of questions.The questions were selected in 2 steps. First, we generated questions by collecting frequently asked questions (FAQs) from health organization, government, medical nonprofit, and other recognized health-related websites . When relevant, we looked for or replicated prevalent general questions across diseases. For instance, as we found the question n most frequent questions, as we wanted to avoid selection biases. The evaluations led us to an insufficient number of questions for AD. This can be explained by the fact that we asked the specialists to select questions that patients would ask their physician, and in the case of AD, information exchange rather happens between the physician and the caregiver, while the patient tends to be less involved [How long can I live with COPD? over What is the life expectancy for a COPD patient?). If the ratings did not result in a clean cut of 10 questions, we defined further selection steps. If there were more than 10 questions, we favored wh-questions  and removed the most ambiguous questions . If there were less than 10 questions, we included questions with lower ratings, always following the criteria mentioned above. Second, we asked practicing medical specialists to think about their medical consultations with patients suffering from the relative type of chronic disease and to rate the frequency of occurrence of the generated field-related question on a 5-point Likert scale . If they deemed it necessary, the specialists were also free to add manually missing frequent questions. For each disease, we recruited 2 specialists, resulting in a total set of 14 evaluations. We intentionally let the medical specialists rate questions in terms of absolute frequency and not ask, for instance, to indicate the involved . Such teThe experiment took place in a meeting room at ETH Zurich, Switzerland, between February 18 and March 4, 2021. Each VA device was placed on a table and tested separately. Two experimenters sat at the two ends of the table. One experimenter submitted the questions to each device through a text-to-speech conversion program  on a lapThe other experimenter took note of the voice responses and the web source through either accessing them on the user accounts (smart speakers) or taking screenshots (display devices). To have a backup of the voice responses, we used an audio recorder .developer and modality, we employed the 3 most common Vas  and aimed for the 2 most frequently used devices  for each VA [voice-only modality and a mix of smart displays (Amazon Echo Show) and smartphones  for the voice-and-display modality. The latter heterogeneity in the devices was due to the unavailability of the Amazon Alexa smartphone application in the authors’ country of affiliation at the time of testing.Based on Kocaballi et al , we test each VA . In partdisplay-only modality and our reference method of  information retrieval, we included a laptop with the Google Search engine (Lenovo ThinkPad X1 Carbon Gen 6 with Google Chrome). We referred to this condition as the web search.Moreover, to operationalize the All devices were set to factory settings, and we used new dedicated accounts, whose history was deleted before testing each device. voice-only and voice-and-display modalities, upon manual start, the text-to-speech program would play the appropriate wake-up keyword , followed by a question. In the case of an error (see the Measures section), we first replayed the question and then, if necessary, played the question again using a male voice. In the case of a persistent error, 1 of the experimenters asked the question manually. This protocol allowed us to ensure the ability to respond to a question did not depend on the input quality. If none of those attempts produced a voice response, we considered the response as not provided. In the display-only modality, the question was directly entered in the text field of the web search engine.The selected questions were played in randomized order. In the Given the involvement of practicing medical specialists, we validated our research proposal (EK 2020-N-173) with the ETH Zurich Ethics Commission. The procedure was approved without reservation on December 21, 2020.R Version 1.2  was used to compute the frequency and descriptive statistics.For the sake of comparison, all results (response rate and source type) are shown in percentages.For each subsection, we first introduce the analysis and then present the results in the form of a table .voice-only modality. Thus, we calculated the percentage of provided answers across developer and disease. We aimed to verify whether there was a pattern in the ability to provide an answer depending on the NCD in question. As the effect of modality was minimal, we present the results for the voice-only modality. Calculating the proportion of source types across developers allowed assessing the presence of information reliability patterns among the VAs. We present the results for the Google showed the highest response rate and rate of expert sources, leading to the conclusion that Google Assistant would be the most reliable tool in responding to questions about NCD management. However, the rate of expert sources differed across diseases.We observed Google Assistant provided the highest response rate, even outperforming the web search results. Apple Siri showed the lowest response rate. This specific advantage of Google Assistant is consistent with previous studies ,32,38,39I found this on the web and presented visually a list of results instead of voicing a unique response. This may reflect a tendency to transfer the responsibility of information retrieval to the patients, whereas they are in charge of choosing (the most) reliable information source. As we believe in the potential of VAs in increasing the accessibility of health information by vocally interacting with patients having their hands occupied or with disabilities [Moreover, Apple Siri often replied bilities -17,19-24expert sources, without outperforming the web search results. Amazon Alexa showed 13.3% fewer expert sources. These results are surprising, given the partnership that Amazon started with the United Kingdom National Health Service (NHS) in 2019, allowing the former to freely access health-related information provided by the latter [expert sources, favoring crowdsourced sources. Importantly, Apple Siri also showed the highest proportion of missing sources . Alagha and Helbing [commercial, crowdsourced, and not stated sources as less reliable than expert sources. As commercial and crowdsourced sources may, in some cases, still provide reliable information [Similar to the results for the response rate, Google Assistant also answered the most frequently with e latter . Finally Helbing  classifiormation ,42, ApplWhen comparing the response rate across diseases, we observed Google Assistant to respond rather similarly across diseases, with a slight advantage for LCA and CKD. Amazon Alexa and Apple Siri showed the highest response rate for LCA. Thus, questions related to LCA seemed to have a general advantage over the other diseases. Both Amazon Alexa and Google Assistant outperformed web search results on both LCA and CKD.expert sources for CVA, while Amazon Alexa did so for DM. Apple Siri showed expert sources only for questions about CVA. Thus, there seems to be an advantage of CVA questions in being reliable the most often, except when those questions are asked to Amazon Alexa.Our results showed Google Assistant to most often use Finally, this slight heterogeneity in results is in line with the diversity in previous research, whereas depending on the condition or disease of interest, reliability varies across VAs -29. HencDespite our best efforts, our study presents some limitations.First, for technical reasons, we employed a smart display instead of a smartphone for Amazon Alexa. The observed similarity in source type proportion between modalities may be explained by the use of 2 types of home devices. This similarity may reflect a consistency in information provision across Amazon Alexa modalities, which is desirable. However, future research should aim to replicate the results by comparing the reliability between the Amazon Alexa app and an Amazon smart speaker. This will support an absence of the effect of interaction modality in Amazon Alexa.Second, to control for the effect of time on the responses, we aimed to restrict the time window inside which to test the VAs as much as possible. Thus, given the high number of questions submitted , we did not submit the same questions multiple times. However, we conducted a post hoc test-retest reliability assessment by randomly selecting 1 question per NCD and submitting each one 10 times to all VAs. Our results showed no variation in the voice responses or the source type. Nevertheless, as observed in previous research that VAs do not always provide the same response , future Third, questions were selected by looking for FAQ pages on health-related websites, but it is difficult to conclude whether all relevant questions were included. As we shared the list of questions see , we hopeexpert, commercial, crowdsourced, or not stated, whereas expert sources represented government and heath nonprofit sources [ered such sources as the mostreliable because they consistently assured good quality of information. However, although not stating a source of information makes it difficult for a patient to judge the response’s trustworthiness, commercial and crowdsourced sources may, in some cases, still provide correct information. Health-related information coming, for instance, from wikipedia.com (crowdsourced) varies importantly in terms of quality [Commercial sources may also contain partly reliable information [Fourth, the source type was categorized based on the work of Alagha and Helbing  and Boyd sources . We cons quality  and coulormation , despiteormation . Future expert source rates for FAQs related to this disease.Fifth, the FAQs about AD were evaluated as rather rarely asked by the patients. As information exchange about AD rather happens between the physician and the caregiver, while the patient tends to be less involved , future Finally, questions were validated by Swiss doctors and thus may not be representative of the patient’s most frequent concerns in other realities. Future research should validate the tested questions with professionals of other countries to ensure their relevance across nations.voice-and-display modality only) to provide expert information for smoking-cessation-related questions compared to the web search. Similar to Boyd and Wilson [health agencies with medical expertise). However, although Boyd and Wilson [voice-and-display and voice-only modalities). The difference may lie in the evaluation of the web search’s responses: although we considered featured snippets as the selected response to judge the search engine on, Boyd and Wilson [first non-advertisement link or information of the list of results. This criterion may have led the authors to collect more responses from the web search and thus a different distribution of reliable sources. Moreover, Boyd and Wilson [Our results are partly in line with the work of Boyd and Wilson , comparid Wilson , we obsed Wilson  found thd Wilson  considerd Wilson  were thenot stated, crowdsourced, commercial, or expert , our study showed an advantage of Google Assistant, followed by Amazon Alexa. The higher advantage of Amazon Alexa observed in our study may be explained by the time of data collection. More specifically, Alagha and Helbing [Based on Alagha and Helbing , who bas Helbing ). Althou Helbing  tested t Helbing   information lookup is truly advantageous and accessible if it can breach the barriers of lack of literacy [In general, most of the related work presented above -29 evaluliteracy ; visual,literacy -24; or mliteracy -17. Onlyliteracy  reportedliteracy , future literacy  and thisAlthough the questions used in the studies discussed above were based on health-related web pages ,29,31, nobtain, process, understand, and communicate health-related information to a level that favors positive health behavior [Complications related to NCDs, such as CVD, cancer, chronic respiratory disease, and DM, are among the main causes of mortality, accounting for 71% and 74% of all deaths worldwide in 2016 ,4. VAs cbehavior ). For inIs the response rate dependent on developers and modality?), observing that Google Assistant responded to most of the answers and Apple Siri responded to the fewest. Modality played a minimal role, whereas Google Assistant and Apple Siri responded slightly more often in the voice-only modality and Amazon Alexa in the voice-and-display modality. Moreover, we answered our second research question , finding that Google Assistant based most of its responses on expert sources of information, even outperforming the web search snippets. Furthermore, Amazon Alexa was less reliable but provided expert sources more than 50% of the times. Finally, Apple Siri was the least reliable, providing a considerable percentage of crowdsourced sources or often not providing a source at all. Across modalities, Amazon Alexa and Apple Siri similarly provided expert sources, while Google Assistant did so more frequently in the voice-only modality. Thus, the variation seemed to be more influenced by developer than modality. Finally, answering our third and fourth research questions , we observed that although there is a slight variation across the diseases, Google Assistant showed a general clear advantage. Nevertheless, although Google Assistant seems to be a good option to ask NCD-related questions, a large number of commercial sources was used, in particular for COPD. Providing patients with unverified or non-evidence-based information may be counterproductive if not dangerous. Therefore, we call out health organizations to collaborate with technology companies, such as Google, Amazon, and Apple, to ensure patients with NCDs are provided with openly reliable  information about the management of their condition. Finally, as the algorithms behind the VAs continuously change, future research should establish the temporal consistency of these results.This study provides evidence of the ability of Vas, such as Amazon Alexa, Apple Siri, and Google Assistant, to provide reliable voice responses to questions related to NCD management compared to the standard consumer-accessible method of information lookup . We validated NCD-related questions with practicing medical professionals, submitted a set of 60 questions to each VA, and assessed the response rate and source type. We answered the first research question (ie, To conclude, our contributions lie in the following aspects. First, to the best of our knowledge, no previous research assessed the reliability of the 3 most prevalent VAs in responding to NCD-related questions. Second, we tested the selected VAs by submitting questions that we validated with practicing medical specialists in terms of the frequency of occurrence in their medical consultations. Third, we systematically controlled for the effect of visual display by testing both smart speakers and display devices for each VA. Finally, as previous research remains rather preliminary and lacks transparent method reporting , we aime


OC of 68 V and the peak ICC of 14.4 μA and 1 μF capacitor was charged successfully in less than 1 s. A wearable chemical sensor was also fabricated and showed a sensitivity up to 53% for nerve chemical warfare agents (GD). DFT calculations were conducted to unveil the fundamental mechanisms underlying the graphene e-fabric sensor. Additionally, protection against chemical warfare agents was tested, and a design concept of graphene-based intelligent protective clothing has been proposed.Conventional or non-conventional chemical threat is gaining huge attention due to its unpredictable and mass destructive effects. Typical military protective suits have drawbacks such as high weight, bulky structure, and unpredictable lifetime. A durable, light, and scalable graphene e-fabric was fabricated from CVD-grown graphene by a simple co-lamination method. The sheet resistance was below 1 kΩ/sq over the wide surface area even after 1000 bending cycles. A graphene triboelectric nanogenerator showed the peak V There are growing demands for protecting individuals from conventional and non-conventional threats such as chemical and biological agents. Current CBR  personal protective suits for military and emergency responders are classified as activated carbon-based permeable (sorptive) technologies and impermeable barrier technologies . They arGraphene and its derivatives can be excellent candidates as protective clothing with multi-functionality such as chemical protection, wearable sensing, flame resistance, and energy harvesting. Graphene has been demonstrated in many applications in the past decade, such as photonics ,5,6, ele2/Si wafers with much better mechanical stability. The mechanical stability of the graphene fabric was tested in the custom-made bending machine over 1000 bending cycles. A triboelectric nanogenerator was fabricated which demonstrated a practical usage of graphene e-textile. A fabric sensor based on graphene for chemical warfare agents was also demonstrated to show practical usage of the graphene fabrics in multifunctional protective clothing. In addition, protection against chemical warfare agents and aerosol was also tested and evaluated.In this study, we fabricated a durable and multifunctional graphene e-fabric for PPE against chemical and biological threats. The graphene on the catalytic metal (Cu foil) was directly put in contact with a transparent and flexible hot melt adhesive layer. The opposite side of the adhesive layer was simultaneously attached to target substrates in the commercial roll laminator. Then, the Cu foil was chemically removed to finish the process. The large-area graphene was successfully transferred onto the adhesive layer, which is strongly bonded to PET and fabric substrates. The graphene fabric exhibited excellent electrical conductivity, comparable with that of graphene indirectly transferred on SiO2. Then, it was maintained for 30 min with 100 sccm of CH4 to grow the monolayer graphene. At the same time, RF (13.56 MHz) plasma power (400 W) was applied to the sample remotely. The initial and working pressures were 1 × 10−3 torr and 1.4 torr, respectively. Large-area graphene was grown on commercially available Cu foil  from Graphene Square Inc . A high-quality monolayer graphene was grown on Cu foil  using an inductively coupled plasma chemical vapor deposition (ICP-CVD) system . The Cu foil was cut into a 10 cm diameter quartz tube furnace and heated to 1000 °C for 1 h with 10 sccm of HHigh-quality CVD graphene was directly used for transfer without any surface treatments. The graphene on Cu foil was bonded to hot melt adhesive EVA(Ethylene−vinyl acetate) film  while the target substrates, including PET and fabrics, were co-laminated on the other side of the film in the commercial laminator. The temperature of the roll was set to 110–120 °C, approximately 20–40 °C higher than the melting temperature of EVA. A temperature lower than 110 °C was not sufficient for the strong adhesion of the laminates. The melting viscosity of EVA film was 650 mPa∙s at 160 °C, according to the manufacturer. The as-grown graphene on Cu foil showed an almost flat surface; however, it was important to ensure conformal contact between the graphene, EVA, and the substrates. For stable and conformal adhesion between these layers, a PET support film was stacked outside of the target substrate during lamination and then removed. The PET film , with a thickness of 100 μm, supported smooth contact between the layers and improved the uniform and strong adhesion. The binding between the layers can be adjusted according to the thickness of the EVA film. It was found that almost any substrates with high-surface roughness formed strong bonds to the EVA film of thickness less than 30 μm. The lamination speed was 30 cm/min. The Cu foil of the laminate was etched in an etching bath ), then the samples were washed with DI water and dried. 2/Si wafer was evaluated using Raman spectroscopy  with a laser excitation wavelength of 514 nm and XPS . The transmittance of the transferred graphene was measured using a UV-Vis spectrometer . The electrical properties of the as-transferred graphene were analyzed using a source meter  with a 4-point probe station with probe spacing of 1 mm. The mechanical stability of graphene transferred onto fabrics was characterized using a custom-made bending tester. The electrical conductivity of the transferred graphene was measured while performing bending tests over 1000 bending cycles. The morphology of the transferred graphene was characterized by atomic force microscopy  and scanning electron microscopy . The roughness of substrates and transferred graphene was investigated using confocal microscopy . The quality of the CVD-grown graphene transferred onto the SiOGraphene e-textile based triboelectric nanogenerator was composed of two parts: the upper part and the lower part. First, 8 × 8 cm graphene transferred fabric was attached to a 10 × 10 cm commercial acrylic plate, which acted as the lower part. Next, 7 × 7 cm commercial aluminum tape  was attached to a 10 × 10 cm commercial acrylic plate and 8 × 8 cm commercial PTFE tape  fully covered on the Al tape. Then, this was used as the upper part. Each lower and upper part was supported by four springs and kept a gap distance of 3 mm. When vertical excitation was applied, the device repeated the contact and separation process. The vertical excitation was provided by a vibration tester , a function generator , and an amplifier . The vibration amplitude and frequency were set as 6 mm and 10 Hz, respectively. The voltage and current output were measured using an oscilloscope  and a preamplifier . The voltage probe 1 and 2 were connected to Al of the upper part and graphene of the lower part, respectively. The voltage output was calculated by subtracting the electric potential of probe 2 from that of probe 1.Graphene e-fabric based chemical sensors were fabricated. Cu electrodes were coated on graphene e-fabric by photolithography. After stabilizing the responses under ambient air, the graphene e-fabric sensor was exposed to a drop (1 μL) of chemical warfare agents. To test the sensor responses, a constant current (10 μA) was applied to the sensor using a source meter , and the voltage drop across the sensors was measured.The interaction of adsorbed GD on graphene was studied using DFT calculations. First, the graphene flake structure with hydrogen-terminated, which was large enough to demonstrate the adsorption of GD, was relaxed using B3LYP functional with 6-31 + G(d) basis set. Once optimized, the coordinates of the graphene flake were fixed to represent the whole structure of graphene. Additional optimization, together with frequency calculation of GD on the fixed model structure of graphene, was performed using the Gaussian 16 program. To calculate the adsorption energy, the single-molecule of GD was also optimized by using the same method. After all calculations, minimum structures were confirmed by checking all positive frequencies. Further analysis on molecular orbital composition by the Hirshfeld method was carried out using the Multiwfn program.2/Si wafer using well-known PMMA supported wet transfer methods [2/Si wafer show no significant macroscopic voids, cracks  fabric, and even onto polyurethane (PU) foam with EVA film.Electrical conductivity is one of the most important features of graphene-based e-fabrics. Several studies have successfully demonstrated a convenient transfer process with excellent electrical conductivity in the range of 1–10 kΩ/sq . Howeverxx) on the graphene e-fabric. The graphene did not experience noticeable damage or degradation during the bending cycles. The sheet resistance was maintained within ±0.6% over 1000 bending cycles. Moreover, after the bending test, the graphene maintained its resistance as it turned on LEDs. This was because of the strong bond between graphene, EVA film and the cotton fabric. These results confirmed that the graphene e-fabric is mechanically stable and can be used as for e-textiles for wearable sensors, intelligent suits, and chemical protective barriers.The mechanical stability of graphene e-fabric is also important to verify the performance under real operational conditions of protective clothing. The electrical conductivity of graphene was measured while performing bending tests, as shown in The graphene e-fabrics were used in the triboelectric nanogenerator (TENG) to verify its electromechanical properties. The TENG system consists of simple four layers, namely the top electrode, two dielectric layers, and bottom electrode. In this study, polytetrafluoroethylene (PTFE) and commercial cotton fabric were used as dielectric layers. The transferred graphene on the bottom of the cotton fabric was acting as a bottom electrode. As the PTFE layer comes in contact with the cotton fabric layer, triboelectric charges are generated on each contact surface via the triboelectric effect. When the PTFE layer undergoes repeated contact and separation process with cotton fabric, free electrons flow continuously between the top and bottom electrodes via electrostatic induction effect. There are various threats for soldiers in combat environments. Chemical warfare agents (CWAs) can be one of the deadliest threats. Many modern protective suits can offer hours of protection against the liquid or vapor phase of CWA. However, it is also important to warn the soldiers of the presence of CWA and the remaining life of their protective garments or equipment. There are many CWA gas sensors, however, most of them focus on gas threats. Those sensors are used for warning troops, not the individuals. It is highly needed to develop a small, wearable, durable CWA sensor for detecting liquid or aerosol CWA threats. The graphene on cotton fabric was used as wearable chemical sensors, as shown in GD/Graphene − (EGD + EGraphene)), it was shown that GD was stably and strongly adsorbed on graphene, illustrating its strong effect on the change of electron energy state of graphene by perturbing the orbitals. Its FMO orbital mixing was proved by molecular orbital composition analysis after HOMO and LUMO orbital compositions were computed by the Hirshfeld method [Density functional theory (DFT) calculations were conducted based on frontier molecular orbital (FMO) theory to understand the electron energy state of graphene in the presence of nerve chemical agent GD (soman). After calculating the ΔE adsorption (Ed method . Low but2). A stream of conditioned air  was drawn across the top of the swatch, and a clean airflow was drawn across the underside for sampling. This dual flow method causes the agent to diffuse onto the body and skin. The configuration of the CWA permeation test is illustrated in To investigate the protective performance of graphene protective clothing, the protection against chemical warfare agents  was tested and evaluated. The graphene e-fabric was cut in standard swatch size (4.5 cm in diameter) for liquid challenge/vapor permeation (L/V) test according to military test standard which, is a required part of acquisition testing for the military chemical protective suits.  The surfThe protection against viruses, biological agents, and radiological particles was evaluated using 100 nm polystyrene particles (similar in size to SARS-CoV-2). The aerosols were generated with an aerosol generator  at 4.5 L/min and neutralized with soft X-ray . The number of PS particles was counted by a particle counter . The aerosol protection was obtained by Equation (1)beforeN is the number of aerosols before filtration by the fabrics, and afterN is the number of aerosols after filtration by the fabricsHere, 2, which was approximately 40% of state-of-the-art protective clothing. In comparison, the aerosol protection for the protective fabric with the outer and a sorptive layer  was only 38.6%, whereas it can provide decent protection against gaseous CWAs. It is believed that the aerosol protection of CBR protective suits can be much enhanced with the addition of a graphene layer with minor sacrifice in weight.The aerosol protection for the fabric, which consists of the outer and the graphene, was almost 100% c. And thBased on the properties of graphene e-fabrics, it is possible to suggest multifunctional, intelligent, protective clothing with graphene where it can provide additional protection to the light sorptive materials and self-powered sensing for the presence of chemical threats. It can also warn the wearers of the permeation of threats, or the lifetime of the protective suit with proper positioning of the e-fabric in the layered protective suits, as shown in We have developed a graphene e-fabric based intelligent multifunctional protective clothing for conventional and unconventional threats. The graphene e-fabric showed excellent electrical conductivity with mechanical stability that can be used for chemical protective clothing. A triboelectric nanogenerator and a CWA sensor were fabricated using graphene protective fabric. A DFT calculation was also conducted and explained the underlying mechanisms in the graphene e-fabric CWA sensor. Finally, the protection against chemical warfare agents showed the possibility of graphene-based intelligent, protective clothing with multi-functionality.