Humans have numerous senses, wherein vision, hearing, smell, taste, and touch are considered as the five conventionally acknowledged senses. Triggered by light, sound, or other physical stimulations, the sensory organs of human body are excited, leading to the transformation of the afferent energy into neural activity. Also converting other signals into electronical signals, graphene‐based film shows its inherent advantages in responding to the tiny stimulations. In this review, the human‐like senses and reflexes of graphene‐based films are presented. The review starts with the brief discussions about the preparation and optimization of graphene‐based film, as where as its new progress in synthesis method, transfer operation, film‐formation technologies and optimization techniques. Various human‐like senses of graphene‐based film and their recent advancements are then summarized, including light‐sensitive devices, acoustic devices, gas sensors, biomolecules and wearable devices. Similar to the reflex action of humans, graphene‐based film also exhibits reflex when under thermal radiation and light actuation. Finally, the current challenges associated with human‐like applications are discussed to help guide the future research on graphene films. At last, the future opportunities lie in the new applicable human‐like senses and the integration of multiple senses that can raise a revolution in bionic devices. It just wants to understand this world with its sensory organs directly. Sensory receptors, neural circuits, as well as parts of the brain involved in sensory perception are included in a sensing system. It is generally thought that sensing systems are those known as vision, hearing, olfaction (smell), taste, and somatic sensation (touch). Through a process of light, sound or other physical stimulations, the object excites the sensory organs of the human body, leading to the transformation of the afferent energy into neural activity.What should be first mentioned is the visual perception, the capacity of elucidating the surroundings via dealing with the information contained in visible light. Retina, the light‐sensitive organ in the back of the eye, is actually an isolated part of the brain serving as a transducer which converts light patterns into neuronal signals. Also transforming light signals to electronical signals, the solar cell (SC) and the photodetector (PD) are photovoltaic regardless of whether the sunlight or an artificial light serves as the source. The second sensory organ is the hearing, which perceives the sound by sensing vibrations, pressure variation of the surrounding medium with time. The eardrum would detect the vibrations, also known as mechanical waves, and then transduce them into nerve impulses. Based on this mechanism, people also developed a series of high‐performance devices which will potentially replace the current techniques, such microphone, loudspeaker, and earphone. The third sense is olfaction, the sense of smell, which is reconciled by specialized sensory cells in the nasal cavity. When odorant molecules bind to specific sites on the olfactory receptors, olfaction occurs and thus detects the presence of smell. Similar to the binding between odor and olfaction receptor neuron, gas sensor would adsorb gas molecules on the surface and induce conductance changes. The forth sensory organ is gustation, also within the five traditional senses, sensing the food or other substances on the tongue. It is the sensation produced when a substance in the mouth reacts chemically with taste receptor cells. Corresponding to the chemical reaction between a substance and taste receptor cells, the biosensor adsorbs the biomacromolecules and react with them. The last sensory organ is the tactile sense or mechanoreceptor, actively exploring surfaces and objects by a subject in movement rather than passive contact of a subject in a static state. This theory would be similar to the emerging devices, such as touch screen, electronical skin, and wearable devices. Additionally, the reflex is a reflection of the cerebral cortex which involves the most diverse stimuli utilized to different sensory areas. A reflex action, different from a reflex, is considered as an unwitting and nearly instantaneous behavior reacting to a stimulus. In other words, the organism will move or act when stimulated. Working the same way, actuated devices would also mechanically respond to the stimulations, such as thermal radiation and photostimulation.Similar to the human sensory organs mentioned above, graphene‐based film shows its great potential in future applications, for instance, light‐sensitive devices, gas sensors and touch devices. As a prevailing member of carbon nanomaterials, graphene has enormous influence on various fields, such as physics and chemistry, materials science and engineering, increasingly transforming into a host of interdisciplinary advances in nanotechnology.SchemeDuring the last few years, numerous advances have been managed in the flexible graphene films with higher quality, greater conductivity and higher transparency. In this review, we provide a summary of current developments focusing on the synthesis, preparation and optimization of graphene film. As is illustrated in 22.1–1 in principle, whose transparency was up to 97.7%. Moreover, graphene is also a good thermal conductive material. The thermal conductivity of monolayer graphene is up to 5.30 ± 0.48 × 103 W mK–1. And the excellent mechanical properties and flexibility of graphene also give it a more promising future of applications, such as serving as flexible sensors and detectors.Similar to the several human organs, the graphene‐based devices mentioned above were also anticipated having excellent performance. Thus the ideal graphene is desperately needed. Compared to the traditional materials, such as conductive glass, the monolayer graphene has extremely low sheet resistance of 30 Ω sq13 cm–2 and the mobility is up to 10 000 cm2 V–1 s–1 in room temperature and 200 000 cm2 V–1 s–1 at low temperature.–1 on nickel (Ni) and copper (Cu).–1 after thermal annealing at 1000 °C.In our human body, neurotransmitters are regarded as the messenger in synaptic transmission, which is essential for the human internal signal transmission. This is comparable to the transfer of the carriers in graphene, which are also delivering the electronic information of graphene. The electrons and holes of graphene in concentrations are up to 10FigureTransparency is desired both in sense human organ and senseless object in our life. For instance, retina is inlayer of the wall of the eyeball, consisting of pigment epithelium layer and sensory layer, which is transparent. For the graphene, it has been characterized to absorb a significant of 2.3% incident white light owing to its only one atom thick.2 hybridization, the graphene also has excellent mechanical properties, such as tensile strength, shear strength and hardness. By nanoindentation in an atomic force microscope, the free‐standing monolayer graphene membrane presented that its Young's modulus is about 1.0 TPa and its fracture strength is of 130 GPa, which established that graphene is the strongest material ever measured.When we touch something, we can find that our skin would deform to a certain extent. And our skin can also be stretched and twist, which provide the possibility for the many activities of human beings. This is attributed to the excellent mechanical properties of shin, which is also found in graphene. Since carbon (C) atoms adopt a trigonal covalent bonding scheme of sp–1), diamond (≈2000 W mK–1) and carbon nanotubes (CNTs) (≈3500 W mK–1), graphene has the optimal thermal conductivity in the range from (4.84 ± 0.44) × 103 to (5.30 ± 0.48) × 103 W mK–1, which offers tremendous potential for graphene as transparent heating films. In Figure –1 as the layer number of graphene increasing from 2 to 4, caused by the interlayer coupling of the low‐energy phonons .Figure 2/Si substrate. The electron mobility of obtained single‐layer graphene reached up to 7400 cm2 V–1 s–1. To further understand the advantage of liquid metal substrates, we also learned the growth behavior of graphene on liquid Cu and indium (In), and it indeed revealed the superiority to solid metals, the optical microscope images were shown in Figure It is worth stressing that, we break a new path to grow graphene film on liquid metal substrates, which is in full swing in recent years.–1 sheet resistances, as the result of the half‐integer quantum Hall effect.–1 was obtained.Besides the monolayer graphene, the production of graphene films with low sheet resistance and vast area should also be taken into account urgently. Iijima et al. successfully obtained 30‐inch graphene films with 97.4% optical transmittance and 125 Ω sqκ SrTiO3 substrates.4. And a monolayer graphene with carrier motilities of ≈870–1050 cm2 V−1 s−1 could be synthesized on single crystal SrTiO3.FigureI2D/IG ratio 2S2O8. After that the graphene film was transferred onto the target substrate ) by removing the adhesive force. This method successfully achieves to transfer the large‐area graphene film, which affording new opportunity for touch devices. However, such graphene films cannot avoid cracks and folds. In order to obtain large‐area graphene without cracks, Loh et al. developed a face‐to‐face transfer method for the graphene films in wafer‐scale, which relied on the gas bubbles and capillary bridges between the underlying substrate and the graphene film during etching of the metal catalyst.In addition, Iijima et al. invented a roll‐to‐roll transfer approach.Inspired by the natural phenomenon of a snail secreting mucus, we developed a novel sliding transfer strategy recently.Until now, significant advances have been achieved during the past years. However, more endeavor still needed to be focused on the larger‐area uniform graphene films with less cracks and wrinkles.Different from the graphene grown by CVD, GO sheets always have been heavily oxygenated, with carbonyl and carbonxyl groups located at the sheet edges, as well as hydroxyl and epoxide functional groups on the basal planes.2–103 Ω sq–1 and with 80% transmittance for 550 nm light. Under different rotating speed, all GO thin films reveal to be with high electrical conductivity and transparency in varying degrees. This route, as well as drop‐casting, is still in widespread use today.Chen and Bao et al. spin‐coated GO dispersions on the prepared substrate and controlled its thickness by adjusting the rotating speed.It's worth mentioning that besides drop‐casting and spin‐coating, vacuum filtration is also an alternative solution for large‐area continuous graphene films. As Chhowalla's group described, by the means of a commercial mixed cellulose ester membrane with an average pore size of 25 nm, they easily realize the vacuum filtration of a GO suspension.In short, towards the high‐quality graphene grown on metal substrate, it is inevitable to etch the metal and transfer the film to target substrates. However, the transfer process is still confronted with the mishap of the cracks and wrinkles on large area graphene film. To the solution processed GO films, the functional groups in some extent sow the seeds for adsorption of various chemical molecules.Optimization: As is known to all, the neurons in human nervous system have special structures, allowing them to send signals precisely and rapidly to other cells. To utilize the graphene film in human‐like sense devices, the promotion of conductivity which is similar to electrical signal transmission is crucial. Although the conductivity of graphene in theory gives it a promising future, the reality does not match with the theory due to various factors caused by the defects and cracks from synthesis and post treatment process. Therefore, chemical heterogeneous doping is a useful method to improve the graphene sheet resistance. SOCl2,2,3,33 chemical doping was the most commonly used way to enhance the conductivity of graphene. When dissolved in a solvent, the ionic conformation in AuCl3 was affected by the amount of coordinating agent. Kong et al. chose nitromethane as solvent of AuCl3.3 doping concentration, the sheet resistance of the graphene film can be decreased to 150 Ω sq–1 with a transmittance of 87%, which can be comparable to the ITO films. However, the instability of the AuCl3 doping would dramatically increase the sheet resistance in the practical applications. To alleviate this problem, Lee et al. proposed a novel layer‐by‐layer (LbL) doping method .The instability of graphene‐dopant coactions in the air or under thermal loading limits its lifetime and thus causes an increase of sheet resistance  network on the top of the graphene film.Recently, Cao et al. developed a blown bubble method which could directly fabricate CNT–graphene hybrid films.Rs by augmenting carrier density, while the graphene‐based hybrid materials can provide more conductive pathways, leading to locally increase in conductivity.In summary, two optimization strategies both could improve the conductivity of graphene films. The chemical doping method can decrease the 33.13.1.1FigureAs we all know, through the eyes, human perceive and assimilate information from the external world. Light entering the eye is refracted when it passes through the cornea, as the –1) and flexibilityThe SCs has long been recognized as a clean energy technology which utilizes the planet's most abundant and widespread renewable energy source—the sun. The technology directly converts sunlight to electricity without any moving parts or environmental emissions during operating process. As a key component of SC, the transparent electrode serves the dual functions: transmittance and electroconductibility, whereas the ITO is most commonly used. And yet, ITO has inevitable disadvantages, such as chemical and thermal instability, high production cost and friable. Driven by the progress in technology and manufacturing scale, more requests have been made on low cost and flexible SCs, which is a territory most semiconductor giants are looking forward to develop but the commercial ITO can hardly achieve. More attractive than ITO, graphene has been incorporated into each aspect of SC due to its extremely high transmittance (97.7%),By virtue of the superior power conversion efficiencies (PCEs), easy preparation, as well as low cost, perovskite SCs with a perovskite‐structured material as the active layer have aroused considerable attention in recent years.x‐heterostructure transparent cathode was utilized to prepare an n‐graphene/p‐Si Schottky junction SC as shown in Figure Multi‐junction (MJ) SCs are those SCs with multiple p–n junctions which produce an electric current reacting to the light with different wavelengths. To absorb a broader range of wavelengths and then significantly improve the cell's sunlight to PCEs, Chen et al. reported a novel “sunlight‐activated” graphene‐heterostructure film with a strong light‐matter interaction at the interfaces.3P2) to form a tunable junction barrier thin‐film light absorber.In 2012, Regan et al. demonstrated field‐effect SCs, using a transparent top gate to regulate the potential barrier and the electric field in a metal‐semiconductor junction for the purpose of separating photo generated electron‐hole pairs.32+/3+ redox couple.Although the conversion efficiency is less than that of the best thin‐film SCs, dye‐sensitized solar cells (DSSCs) can be designed into flexible sheets whose price/performance ratio are high enough to compare favorably with fossil fuel electrical generation. As it discussed in the previous section, doping heteroatoms into a graphitic carbon framework is an efficient way to activate graphene and to enhance its conductivity. Baek et al. reported that boron‐doped (B‐doped) graphene (BG) is prepared and tested as a counter electrode (CE) in DSSCs in conjunction with Co(bpy)As another type of human‐like light‐sensitive device, graphene‐based PD has received an enormous amount of attention due to the wavelength‐independent light absorption and high operating band width of graphene.–1 which is suitable for most applications.5 electrons per photon.–1 and a fast response time of ≈100 μs. Analogous to this, researchers also introduced other additives into the graphene‐based PD for improving the responsivity, for instance, boron nitrideZhong et al. reported an ultra‐broadband PD design based on a graphene double‐layer heterostructure, demonstrating a mid‐infrared responsivity higher than 1 A WIn summary, several strategies have been adopted to enhance the PCE of the SCs and the photoresponsivity of the PD via the appropriate modification of graphene films. Corresponding to the transparency and nerve impulse of light‐sensitive human eye, the transmittance and carrier dynamics are essential for the SCs of graphene films, which have made rapid progress.3.1.2FigureHearing, or auditory perception, perceives the sound by sensing vibrations, pressure variation of the surrounding medium with time, via an organ such as the ear. The eardrum would detect the vibrations, also known as mechanical waves, and then transduce them into nerve impulses. The human ear consists of three main components: the outer ear, the middle ear, and the inner ear Figure8a. TheIn 2011, Ren et al. first patterned graphene on paper substrates and demonstrated that graphene can emit sound.FigureSince then, Ren et al. developed a high‐efficiency route for the fabrication of real graphene earphones using laser‐scribed graphene (LSG).Zettl et al. presented a graphene‐based wideband microphone and a correlative ultrasonic radio that are expected to be used for wireless communication.FigureMeanwhile, Zhu et al. fabricated a wearable and high‐precision sensor with thin films of well‐designed graphene woven fabrics (GWFs) for the sound signal acquisition and recognition.3.1.3Olfaction is mediated by specialized sensory cells in our nasal cavity. For human, olfaction occurs when odorant molecules combine with the receptor, which will produce an action potential. The responses to an odorant molecule can be characterized by measuring the electro‐olfactogram or calcium imaging of receptor neuron terminals. Put the same point the other way around: can we detect the variety of gas molecules in the environment by fabricating similar devices with our olfaction receptor neuron?2 g–1, high carrier mobility of 200 000 cm2 V–1 s–1, high carrier density of ≈1012 cm–2 and low resistivity of 10–6 Ω,Figure2O;2;2) and increase as the adsorption of the electronic donors .As one of the most anticipated materials in the future, graphene also can be used in gas sensor attributing to its large theoretical specific surface area of 2630 m2, H2O, CO and NH3. What's more, the graphene‐based gas sensor also allowed the maximum sensitivity for detecting individual gas molecules. Furthermore, the graphene film grown by CVD methods also can be used to fabricate gas sensor. Wlodarski et al. reported that the adsorption of O2 molecules on monolayer CVD graphene can result to significant changes of the electrical resistance.2 of 100 ppm and NH3 of 1%. And NH3 can be selectively detected from CH4 or H2, which shows an excellent selectivity.The mechanical exfoliated graphene was firstly used to fabricate graphene‐based gas sensor,2 and Cl2 after reduced by ascorbic acid, whose limit of detection (LOD) was up to the range of 100 ppm to 500 ppb.2 than the pristine rGO.In order to improve the performances of graphene‐based gas sensors, including the sensitivity and the selectivity, functionalized graphene was used. GO with a certain amount of oxygen groups was fabricated as gas sensors after a chemical or thermal reduction process. Here the oxygen groups can act as adsorption sites, which would make the gas molecules easier to adsorb on the graphene. By forming GO continuous film on an insulating substrate from the aqueous dispersion, Sheehan et al. fabricated GO‐based gas sensors.2O nanowire was also used as a hybrid source to compound with rGO sheets, which have enhanced the response for 2 ppm NO2 from 22.5% to 67.8%.2O, which showed a significantly enhanced sensitivity.Another way to achieve highly sensitive detection of various gas species is to hybrid the graphene films with other species, such as nanoparticles, polymer and so on. The hybridization of metal or metal oxide nanoparticles with graphene has demonstrated a significant synergistic effect towards gas sensing. These hybrids possess modulated electronic properties, enabling them to enhance the selectivity and sensitivity. For instance, vertically aligned ZnO nanorods was utilized to prepare hybrid material with chemically converted grapheneFigure2 were fabricated and thus a sub‐nanomolar detection limit of 0.3 nm NO was achieved. What's more, the sensitivity has also been confirmed in physiological solutions and the real‐time detection of NO released from macrophage cells  by the transducer element which plays a part in an electrochemical or physicochemical way. As for graphene film‐based biosensors, the final signals generally are electrical signals, and graphene will serve as a highly conducting network . With high specific surface area and excellent electrical conductivity, graphene works the same as or even better than the “sensory neuron” which could transfer the electrical signals rapidly and accurately.The gustation is categorized into five elementary tastes . Taste buds can differentiate various different tastes through interactions with different molecules and ions. Sweetness, bitterness, and umami are induced by the binding of the molecules to G protein‐coupled receptors on the cell membranes of taste buds. Sourness and saltiness are sensed when hydrogen ions or alkali metal come into the taste buds, respectively.–7m, 2.2 × 10–6m and 4.5 × 10–8m, respectively.2O2 generates in various enzymatic reactions. Zhang et al. designed PSSA‐g‐PPY functionalized graphene to detect H2O2, which can also be used to detect hypoxanthine in fish samples.Sweetness is due to sucrose, glucose, etc. The gustation of sweetness is just like the sensing of small biomolecules. Dopamine (DA), ascorbic acid (AA) and uric acid (UA) are regarded as the three kinds of small biomolecules that have important effects in physiological features of organisms. Sheng et al. investigated the sensing performance of N‐doped graphene for these molecules and got detection limits of 2.5 × 10Sourness is generated from hydrogen ions of HCl, acetic acid or citric acid. The gustation of sourness is just like the sensing of pH. pH is of great concern to all life forms. A number of biosensors based on graphene films have been utilized as pH sensors in the past few years. Among these biosensors, different approaches have been utilized to monitor pH such as SGFETs sensors, GO‐based fluorescent sensors, electrochemical sensors and chemiresistors sensors. Graphene and derivates with large π–π conjugated system itself can be hybridized with pH sensitive fluorescent molecules. Therefore, the detection of fluorescent intensity based on GO is another effective strategy for pH sensing. Hsieh et al. constructed GO‐based nanoplatforms to monitor cellular pH, which achieved both pH sensing and pH‐dependent drug delivery.2, quinine and caffeine. The gustation of saltiness is just like the sensing of metal ions. For graphene film–based biosensors, the sensing of heavy metal ions is of much importance. Being very toxic in human beings, heavy metal ions are of extreme concern. Numerous sensors of heavy metal ions based on graphene have been widely studied since their extraordinary properties were revealed. A variety of heavy metal ions  have been well detected via these graphene‐based sensors.Saltiness is generated mainly by NaCl while the bitterness is generated by MgCl–10 to 1.0 × 10–3 g L–1 and a detection limit of 3.09 × 10–11 g L–1. Zhuo et al. conducted a sensing system of thrombin based on ferrocene–graphene sheets.32+ tagged thrombin, they obtained a low detection limit of 2.1 × 10–10m. Afterwards, Xue et al. constructed a more effective sensor for thrombin: except from ferrocene, they also introduced CDs and AuNPs to modify graphene.–18m. As the carrier of hereditary information, DNA has attracted the attention of researchers for many years. Bonanni et al. immobilized hairpin–DNA probes onto graphene to fabricate a sensor to detect single nucleotide polymorphism relevant to the development of Alzheimer's disease.The last taste is umami, which is a Japanese term for “deliciousness”, triggered by disodium guanylate in mushrooms, monosodium glutamate in seaweeds, and disodium inosinate in meat and fish. Umami is produced by the binding of the molecules to the G protein‐coupled receptors on the surface of taste buds. Protein is one of the fundamental constituents of human bodies, also an important research target because it is the bridge between genes and physiological activities. An accurate and fast detection of proteins is also attractive to researchers. Conventional methods to detect a certain protein usually require corresponding probe molecule. Graphene here can be a substrate that provides enough active sites to immobilize these probes and enhance the electron transfer. Wang et al. introduced a kind of ionic liquid modified graphene‐based bovine hemoglobin (BHb) sensor and conduct the electrochemical determination of the target protein.Just like humans, graphene‐based films also have their sensing. The gustation is categorized into five elementary tastes . And the graphene based‐films can be utilized for the sensing of small biomolecules, pH, metal ions, proteins and DNA. In the future, electronic tongue made by graphene‐based films may come into our lives which can be used to “taste” the flavor of foods. Besides, wireless bacteria detectors based on graphene Figure  e–g may 3.1.5FigureThe touch sense of itching caused by insect bites or allergies involves special itch–specific neurons in the skin and spinal cord. These various tactile sensors are obtained from the specialization of the nerve ending. Nerve cell can be activated when mechanosensitive ion channels are stimulated by pressure, later, electric signal spreads to the brain along the nerve fibers and then transforms into tactile sense which can be felt. Complicated tactile sensing system under bland skin is illustrated in Figure 2 area with a sheet resistance of 249 ± 17 Ω sq–1. Notably, the graphene/PET films are transparent for all visible wavelength range, nevertheless, the ITO appears to be slightly yellowish and less transparent in short visible wavelengths.Iijima et al. fabricated a large‐area graphene/PET touch panel.Tuukkanen et al. fabricated transparent and flexible, water‐proof piezoelectric touch panels Figure b with grAnother type of touch sensors is piezoresistive sensor that convert the pressure applied on the sensor to resistance signal.FigureIn addition, ever‐growing piezoresistive graphene‐based devices are used for detecting feeble movement or deformations of human bodies. Park et al. created a graphene‐coated polymer film as a transparent piezoresistive strain sensor.Recently, wearable interactive human–machine interface (iHMI) systems have attracted attentions due to their applications in personal mobile electronics and the internet. Kim et al. developed a transparent and stretchable iHMI system made of wearable mechanical sensors and stimulators.FigureZhu et al. reported a highly strain sensitive graphene‐based electromechanical sensor with a gauge factor of 500 below 2% and 104 over 8% through tailoring the graphene integral network configuration, crack formation, and propagation mode.In short, skin‐like graphene‐based pressure sensing devices have aroused tremendous attention for flexible devices, especially touch screens, piezoelectric sensors and wearable devices. It just like the graphene films that could readily distinguish various strain levels of outer signals. Furthermore, these applications toward going light, wearable, self‐powered electronics will be required in the future.3.2FigureReflex action is a spontaneous and momentary movement in response to a stimulus Figure19. In When an organism is exposure to the light or thermal radiation, it will tend to get closer or further, which is similar to the photo‐thermal actuated graphene devices. The transparent soft actuators were successfully fabricated by using large‐area graphene, which showed ultrasensitive responses.Figureb). This smart widges fabricated by designing graphene was operated under IR laser control which was not required any additional external stress.By elevating the temperature of the materials, different degree expansion was carried out to make the devices move. The rGO‐CNT/PDMS bimorph photoactuators were introduced by Chen et al.Similar to humans, the graphene actuators responded not only to the photic and thermal stimuli, but also to the watery and electric stimuli. A single‐fiber walking robot was successfully achieved by utilizing graphene/graphene oxide (G/GO) fibers, which prepared by partial asymmetric positioning laser reduction of freshly spun GO fibers.2 plasma respectively, and the actuation motion was induced through asymmetric electrochemical charging and discharging. Graphene–PDA bimorph actuator is also designed by using a simple yet versa tile method.By asymmetrically modifying the surface of monolithic graphene film, a novel graphene electrochemical actuator was successfully achieved by Dai et al.4Sensing is the response to the objective characteristics , or the stimulation from the material world directly affecting the sense organs of the organisms, such as light cause the vision and sound waves give rise to the hearing. As we known, there are no authentic sensations in the inorganic world except for the similar features with sense, which is the pure chemical or physical reflection. Since life appeared on earth, simulated sensitivity including the sprout of feelings comes into being. Humans have a multitude of senses, wherein sight, hearing, taste, smell, and touch are the five traditionally recognized senses. With the stimulation from external world, the corresponding signals would be transduced into electroneurographic signals. In analogy with this theory, we were surprised to see that graphene‐based films exhibit sensing and reflex in similar features to human. Due to its superior characters such as high conductivity, HCPUA, high specific surface area and flexibility, graphene was increasingly utilized to sense the light, sound, pressure and so on. Based on our brief journey to graphene and graphene ramifications, it can be concluded that graphene is a unique two‐dimensional material, offering an extensive range of opportunity for human‐like stimulated sensitivity. That is the very reason makes us lift our eyes to the broad horizon ahead, wishing one day to realize the high‐fidelity artificial organs. However, challenges still remain regarding the ultimate features achievable via operable techniques.Rs ≈ 30 Ω sq–1 of graphene in theory is attractive but hard to achieve. As for the current research situation, the graphene‐based film is still about 1 order of magnitude higher in sheet resistance than ITO. This means that graphene has to be either doped or hybridized with other material, decreasing its sheet resistance. It's worth noting that the instability of graphene–dopant interactions in air and under thermal loading limits its lifetime and thus causes an increase of Rs. The graphene hybridized with other materials, such as CNTs and metal nanowires, can facilitate the low‐cost and high‐speed fabrication of graphene‐based films.Like nerve conduction velocity effected by neurotransmitter, it is not a stretch to think of at least a relation between the human‐like stimulated sensitivity and the quality of the graphene films. CVD growth and solution processing for graphene films attract more attention for their scalability, but domain or sheet size and defect controls are the pivotal issue. The sheet resistance of graphene films is related to the synthesis method. The ideal Before applied to the artificial organs, graphene films should be first utilized for operable electronical devices. Similar with the light‐sensitive human eyes, graphene film serving as the electrode for SC or PD converts light signals into electronical signals. The photoelectric conversion efficiency is affected by the conductivity and transmittance of the graphene film. According to the thin and flexible graphene film, it is reasonable to be applied to the sound generators, such as a microphone, an earphone and a recorder. What is crucial in sound generators is the ultra‐small HCPUA than other materials. And it worth noting that the defects or functional groups on graphene films facilitate the adsorption of various molecules, both small gas molecules and biomolecules. Working like the nose and tongue of humans, the graphene films in gas sensors or biosensors adsorb molecules and react with them, as a result of the changes in conductivity or other properties. Like the touch of humans, graphene films can also sense pressure, friction, and touch. Serving as the component of the touch screen, wearable devices and piezoelectric devices, graphene films exhibit high sensitivity and flexibility. Apart from these five traditional senses mentioned above, graphene films also demonstrate mechanical motion once stimulated by thermal radiation, light, or humidity, to name a few. Although dramatic progress has been made in this field, great challenges still exist in commercializing applications of graphene. The challenges can be summarized as follows: (1) make a balance between low sheet resistance and extremely high transmittance. (2) the preparation of large‐area devices for more emerging applications such as artificial skins and intelligent interfaces.Except for the general senses, there are several non‐traditional senses of human, such as balance, acceleration, temperature, kinesthetic sense, and pain. On account of this, pushing into new territories of human‐like senses gives a new estimate. In addition, to realize high‐fidelity artificial organs, we need to develop the integration of multiple human‐like senses of graphene films. And, once achieved, we firmly believe that graphene will raise a revolutionary of human‐like senses and reflexes, paving its flourishing way to future commercial devices.


Unraveling the doping-related charge carrier scattering mechanisms in two-dimensional materials such as graphene is vital for limiting parasitic electrical conductivity losses in future electronic applications. While electric field doping is well understood, assessment of mobility and density as a function of chemical doping remained a challenge thus far. In this work, we investigate the effects of cyclically exposing epitaxial graphene to controlled inert gases and ambient humidity conditions, while measuring the Lorentz force-induced birefringence in graphene at Terahertz frequencies in magnetic fields. This technique, previously identified as the optical analogue of the electrical Hall effect, permits here measurement of charge carrier type, density, and mobility in epitaxial graphene on silicon-face silicon carbide. We observe a distinct, nearly linear relationship between mobility and electron charge density, similar to field-effect induced changes measured in electrical Hall bar devices previously. The observed doping process is completely reversible and independent of the type of inert gas exposure. These materials have wide spread applications such as high-frequency electronics, sensing elements, mechanically durable and lightweight materials, medicine, energy storage, and more. Common to all two dimensional materials is their extremely large surface to volume ratio, which make them very susceptible to substrate and ambient gas adsorption effects. Graphene, one of the most studied two dimensional materials, has been shown to substantially change in its properties as a function of substrate, substrate polarity, and ambient media 11. Ambient induced doping is observed for many types of graphene, for instance epitaxial graphene on SiC7, exfoliated graphene on SiO28, and chemical vapor deposition (CVD) grown graphene9. However, the effect of ambient doping on the free charge carrier mobility is rarely explored, mostly due to the lack of experimental techniques capable of independently assessing carrier density and mobility without further modifying graphene. For instance standard electrical Hall effect measurements require contacts and Hall bar fabrication, which involve multiple processing steps that may modify graphene properties. In this work, ambient effects on the free charge carrier density and mobility of epitaxial graphene grown by Si-sublimation on the Si-face (0001) of 4H-SiC is studied as an example12.Two dimensional materials are a new class of materials that attracted significant interest due to their unique electronic, optical, and mechanical properties. Many properties differ dramatically from the bulk substances. Examples include silicene, molybdenum disulfide, hexagonal boron nitride, and graphene14. The intrinsic electron doping of pristine monolayer epitaxial graphene on Si-face SiC was found to be on the order of 1013 cm−2 6. The polarity of the Si-face SiC also gives rise to high hydrophilicity, which is relatively unchanged with addition of a graphene monolayer15. Similar to other two dimensional materials, graphene’s properties are also extremely sensitive to adsorbed gas molecules17. Previous studies of the electrical properties of epitaxial graphene on SiC as a function of the ambient conditions employ contact-based techniques or Kelvin probe approaches and typically do not report changes in Ns and μ simultaneously. For example, the authors in Ref. Ns and μ simultaneously. In order to fully understand the ambient doping and scattering mechanisms in epitaxial graphene, accurate information on the free charge carrier parameters as a function of the ambient conditions is required. Here we report on the first in-situ, contactless determination of the majority free charge carrier type, Ns, and μ using terahertz-frequency optical Hall effect measurements (THz-OHE)20. We expose a monolayer graphene sample to various gases and report the results of the best-match model data analysis from optical Hall effect measurements. Along with Ns and μ, the THz-OHE signal allows us to determine the majority free charge carrier type (electrons). This is important information since the majority carrier type of epitaxial graphene on Si-face SiC can vary from sample to sample22. We find that exposure to ambient causes significant changes in the free charge carrier properties sheet carrier concentration Ns and mobility μ for epitaxial graphene on SiC.This type of graphene typically exhibits n-type conductivity due to a complex interaction with the Si-face SiC substrates via the buffer layer18. The sample investigated here consists of 99% monolayer (ML) graphene and 1% bilayer (BL) inclusions as illustrated in a representative microscopic reflectance-converted-thickness map in Fig. Figure in-situ optical Hall effect best-match model results for sheet carrier density Ns and mobility μ as a function of gas exposure for the ML graphene sample. After growth, the sample was exposed to normal ambient conditions (air measured with relative humidity (RH) of 45%) for approximately 15 minutes, and then mounted in the gas flow cell. During the experiment, large dynamic changes in Ns and μ are observed when changing the gas type. It can be seen that nitrogen and helium exposure (both 0% RH) increases Ns while ambient exposure (45% RH) decreases Ns. This behavior is consistent with previous results on epitaxial graphene on SiC16. The change in Ns from air exposure can be explained by a redox reaction at the surface of the graphene involving various environmental gases, which results in electron withdrawal5. Exposure to an inert gas, such as nitrogen or helium, is thought to cause the doping agents at the graphene surface to desorb, which reverses the electron withdrawal.Figure Ns and μ. We observe an approximate single process exponential decay with mean life time τ for both quantities, where the exposure to helium results in faster changes (τHe ≈  45 min) than the exposure to nitrogen (τAir ≈ 20 min) faster than the observed changes during the exposure to the inert gases. We estimate the equilibrium electron density  and mobility  parameters for infinite exposure time of helium, nitrogen, and air as 2.2 × 1012 cm−2 and 1960 cm2/Vs, 1.9 × 1012 cm−2 and 2100 cm2/Vs, and 8.8 × 1011 cm−2 and 2530 cm2/Vs, respectively. There is a noticeable difference in Ns,∞ and μs,∞ for He and N2 exposure. The cause of this difference is unknown at this point. The difference may be explained by more effective impurity desorption from He compared to N2, or in different modifications of the graphene-SiC interaction.The prolonged exposure of single-layer graphene to inert gases drastically changes Ns shown in Fig. 2, H2O, and CO25. To summarize this previously proposed mechanism, first thin films of water form at surfaces when exposed to ambient. These films contain dissolved CO2, which reacts with water causing an excess of H+. O2 dissolved in the water film reacts with H+ and electrons borrowed from the graphene and forms additional water molecules, thereby chemically acceptor doping the graphene. While this reaction may not be the only possible chemical process, it is described as the most dominant23. In principle, it is also possible that the observed changes in Ns and μ may be related to a modification of the Van der Waals interaction between Si-C and C-C at the SiC-graphene interface. However, exposure to ambient and different inert gases of bare SiC substrate and a sample containing only a buffer layer grown at the same conditions as the epitaxial graphene show no change in the THz-OHE signals. We also note that both SiC substrate and the buffer sample do not produce any free charge carrier related response.One possible scenario explaining the observed time evolution of μ and conductivity σ are plotted as a function of Ns in Fig. μ versus Ns. Figure Ns, where σ = Nseμ and e is the electron charge24. Interestingly, the same nearly linear dependence of μ versus Ns with time is observed regardless of the type of gas exposure. Since different scattering mechanisms produce different functional dependencies of mobility versus density, one might anticipate that exposure to different gases would result in different traces of μ versus Ns. However, the observed common traces for He and N2 suggest that the scattering mechanisms which cause variations in μ are similar. The common traces for inert and ambient gases suggest that inert gases reverse the scattering mechanism influence from air exposure.In order to investigate the free charge carrier scattering mechanisms, which are affected by the observed chemical acceptor doping of graphene, μ as a function of Ns, Matthiessen’s rule is applied to combine a constant mobility contribution μconst and an Ns-dependent contribution μn ~ 1/Ns  scattering, and μn represents the Ns-dependent point (short range) scattering contribution27. In contrast with our work, the ambient conditions were not varied in the experiments performed by Tanabe et al. Therefore, our experiment may include different contributions to charge carrier scattering and further experimentation is needed to determine the exact source of mobility limitation. Furthermore, the fabricated Hall bars and electrodes in Tanabe et al. may introduce additional contributions to carrier scattering compared to our virgin sample. In Tanabe et al., the number of charged impurities is likely not to vary throughout the experiment, unlike this work in which impurities can be introduced by gases. Our observation suggests that it is possible only the carrier density in the graphene changes as a result of gas exposure and where the observed change in mobility is only given by the μ(Ns) dependence. This would also provide a possible explanation why both μ(Ns) and σ(Ns)  are μconst = (3214 ± 35) cm2/Vs and a = (1.20 ± 0.03) × 1016 (Vs)−1, where a is the proportionality constant in μn = a/Ns clearly describe all observed data points. Note that parameter a does not necessarily correspond to any specific scattering mechanism, but is reported here to describe the observed relationship.In an attempt to apply a model for Ns Fig. 25, 26. Ts) Fig.  show so μ versus Ns dependence35. In the report by Yager et al., many Hall bar devices were fabricated and investigated on primarily 1 ML graphene. In contrast to our work, the variation in Ns reported by Yager et al. is a result of variation of small 2 ML coverage inside certain devices. In Ref. Ns, μ, and carrier type.Recent electrical Hall bar experiments on very similar epitaxial graphene also show a linear Ns and μ of epitaxial graphene as a function of gas exposure using the cavity-enhanced in-situ THz-OHE, which allows contactless determination of these properties. In addition to the free charge carrier properties, the THz-OHE allows access to the majority carrier type, which is determined to be electrons. The results of the best-match model analysis reveal important information about the ambient doping and scattering mechanisms for epitaxial graphene on Si-face (0001) 4H-SiC. In agreement with previous works6, it is found that exposure to an inert gas, such as helium or nitrogen, reverses the electron withdrawal caused by ambient. The change in Ns and μ as a function of gas exposure can be approximated by a single process exponential decay function. The results indicate epitaxial graphene on Si-face SiC could take longer than one day to reach its final ambient state. This is important to consider when studying graphene recently exposed to ambient, since its properties may differ from day to day.In summary, we have obtained μ versus Ns dependence is universal for all phases of gas exposure. This suggests inert gases reverse the scattering mechanism influence caused by air exposure. When a model is applied for μ as function of Ns, we find one constant and one ~1/Ns term is needed to describe the dependence. This suggests that it is possible only the carrier density in the graphene changes as a result of gas exposure and where the observed change in mobility is only given by the μ(Ns) dependence. This scenario also provides explanation for the observed universality of μ(Ns) and σ(Ns) dependencies on the gas species. However, further investigation is needed to distinguish the exact mechanisms which control and limit μ. The experiments performed here demonstrate the ability of the in-situ THz-OHE to obtain Ns, μ, and majority carrier type with a high time resolution which is valuable for characterizing two-dimensional materials. Examining the relationship between these properties enables insight into the doping processes and scattering mechanisms as function of environmental variables.The observed 19. A tunable, externally-coupled cavity is used to enhance the THz-OHE signal, which allows the accurate determination of a sample’s free charge carrier properties even at low magnetic fields. Placing the sample near the THz reflective metal surface of the permanent magnet allows the typically unused radiation emitted out the backside of the sample to be reflected back in . The parameters were determined by a point-by-point analysis, meaning Ns and μ were determined by a fit process to the experimental data obtained for each point in time separately.To obtain the parameters m* is not obtained in the analysis and has been implemented as function of Ns using the equation νf = 1.02 × 106 m/s is the Fermi velocity, according to Ref. m* in addition to Ns and μ18. However to improve the time resolution of the in-situ measurement, experimental data was only obtained at one frequency ν = 428 GHz, one angle of incidence Φa = 45°, and one sample-magnet air gap distance dgap = 100 μm. If one or more of these variables were utilized during the in-situ measurement the sensitivity to all free charge carrier properties would increase.Due to experimental constraints, effective mass During data analysis, to correct for slight misalignment of the THz ellipsometer we employ one frequency- and time-independent correction matrix in the optical model. The correction is made by matrix multiplication of the Mueller matrix representing the sample-magnet system and a correction matrix representing a small constant offset induced by the instrument. To find the correction matrix values used in the analysis, all the elements of that matrix were fit to data obtained at multiple frequencies (385 to 395 GHz) before the gas flow experiment. In this spectral range, there are no changes due to the sample or magnet, but only changes from minor instrument non-idealities.ν = 428 GHz) as a function of time for different gas exposures. The Mueller matrix elements depicted here are M12 and M23. For this sample and permanent magnet configuration, the M12 element experiences the largest change with variation in the free charge carrier properties. The frequency ν = 428 GHz was chosen because this is where the maximum change in M12 occurs. The M23, as well as all other off-block-diagonal Mueller matrix elements, characterize the THz-OHE signal and would be zero if there were no magnetic field present. The negative value of this element indicates the sample is n-type, since the sample is mounted on the north pole-face of the permanent magnet. Note that a sign reversal of this element would indicate a reversal of conductivity from n-type to p-type. Such type of change, for example, can be induced by use of reactive gases such as NO216.Figure M21 and M32 are omitted due to being essentially equal to M12 and M23 respectively. M13 and M31 are essentially equal and are omitted since they resemble M23. M22 and M33 show very little change and are omitted.Breaks in the experimental data near the end of each gas flow phase are where data was obtained at multiple frequencies to verify the optical model. This is verification was done before the point-by-point analysis was performed. Data recorded prior to those reported here were taken during repeated gas exposure cycles, and were found highly reproducible. Note, certain Mueller matrix elements are excluded for brevity. The


Traditional Chinese medicine (TCM) has a long history in the treatment of psoriasis vulgaris. We aimed to evaluate the clinical efficacy and safety of Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood-heat syndrome.A multicenter, randomized, double-blind, placebo-controlled trial was conducted. Participants with psoriasis vulgaris of blood-heat syndrome were blinded and randomized to receive Pulian ointment or placebo ointment twice daily for 4 weeks, with follow-up 8 weeks after treatment. Psoriasis Area Severity Index (PASI) scores, severity of each symptom and area of skin lesion and quality of life were assessed at baseline, 2 weeks, and 4 weeks. Adverse events were recorded during the study. SAS 9.4 software and SPSS 17.0 software was applied for data analysis.P < 0.05). However, no significant differences were observed in scores of scaling, erythema and induration/thickness (P > 0.05). Per protocol set (PPS): There was no statistically significant difference in PASI score and separate score of each symptom and area of skin lesion between two groups (P > 0.05). Quality of life measured by Hamilton Anxiety Rating Scale (HAMA) and 36-Item Short Form Health Survey (SF-36) improved after treatment in both groups, but there was no significant difference between the two groups (P > 0.05). After being followed up for 8 weeks, the total relapse rates of the Pulian Ointment group and placebo group were 5.88 and 8.45%, respectively, and the difference was not statistically significant between the two groups (P > 0.05). No adverse event was observed in both groups throughout the study.A total of 300 participants with psoriasis vulgaris of blood-heat syndrome were assessed for eligibility, and 294 were randomly assigned to the Pulian ointment and placebo group from six study centers. Full analysis set (FAS): after 4 weeks of treatment, there were significant differences between groups in PASI score and the separate score of skin lesion area, favoring Pulian ointment group (Pulian Ointment seems effective and well tolerated in improving the PASI score and separate score of skin lesion area for patients with psoriasis vulgaris of blood-heat syndrome. Further research could build on the current study to explore whether other preparation forms and greater intervention intensity are necessary for better therapeutic effects.ChiCTR-TRC-12002054.Chictr.org.cn Identifier The online version of this article (doi:10.1186/s12906-017-1631-5) contains supplementary material, which is available to authorized users. Psoriasis is a common chronic immune-mediated inflammatory disease of skin and joints. Psoriasis vulgaris is the most common type of psoriasis. Estimates of the worldwide prevalence of psoriasis range from of 2 to3 % . In ChinCurrently, there is no cure for psoriasis. Conventional western medications, such as methotrexate (MTX), acitretin A and ciclosporin, are limited for long-term use due to their limited efficacy and/or various potential toxic and side effects. The introduction of new biologic agents has increased the therapeutic options for the treatment of psoriasis, however, because of their high price, potential side-effects and unclear long-term efficacy and safety new biologic agents have not been widely used.Traditional Chinese medicine has a long history of treating psoriasis based on specific syndromes, such as blood-heat syndrome. Pulian Ointment, an external therapy of Chinese herbal medicine, is a prescription developed by a famous traditional Chinese medicine practitioner, Bingnan Zhao. Pulian Ointment is used to clear excess heat and dampness, and relieve swelling and pain. Since the opening of China-Japan Friendship Hospital in 1984, Pulian Ointment has been used as a hospital prescription in the treatment of blood-heat syndrome psoriasis, and has been registered with the Beijing Food and Drug Administration . Our previous retrospective study showed that 3 weeks of treatment of psoriasis vulgaris by Pulian Ointment combined with oral Chinese medicine was superior to 5% boric acid ointment group in the total effective rate, and no adverse events were reported during the study [ 448). OuThe objective of this study is to explore the clinical efficacy and safety of Pulian ointment in the treatment of participants with psoriasis vulgaris of blood-heat syndrome by external application.This was a multicenter, randomized, double-blind, placebo-controlled study conducted in six centers in China. The six centers were as follows: China-Japan Friendship Hospital, Beijing Hospital of Traditional Chinese Medicine (TCM), Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Guang’anmen Hospital and Air Force General Hospital and Chinese People’s Liberation Army (PLA). Participants were outpatients or inpatients of Department of Dermatology. All personnel involved in this study undertook a training course including the study protocol, investigators’ responsibility and research monitoring, and relevant skills such as TCM syndrome differentiation. Manual for Investigators were also provided to each center.Clinical Dermatology (3rd Edition) edited by Bian Zhao et al. [Diagnosis of psoriasis vulgaris was based on the o et al. : acute oGuiding Principles for Clinical Research on New Drug of Traditional Herbal Medicine (1st Edition) [Diagnostic criteria of TCM blood-heat syndrome was based on the Edition) : primaryParticipants were included in the study if they were diagnosed as psoriasis vulgaris of blood-heat syndrome based on diagnostic criteria of psoriasis vulgaris and TCM blood-heat syndrome; aged between 18 and 65 years old; had skin lesion area < 30%; and willing to sign the informed consent form.Participants were excluded if they had infection or trauma; during pregnancy or delivery; systematic or external local application of corticosteroids or immunosuppressant within 1 week before inclusion; severe heart, liver or kidney diseases; mental diseases; allergic history of general or local allergic responses to any Chinese herbal medicine or matrical ingredient of Pulian ointment or placebo used in this study.Central block randomization method was applied in this study. Participants were randomly allocated into Pulian Ointment group or placebo group for 4 weeks. Follow-up period lasted 8 weeks after study completion. The randomization ratio was 1:1 in blocks of 2. Random numbers were generated by an independent third party  using SAS PLAN statement for random sequence generation. Then randomization codes made by the third party were labeled to the internal and external packages of Pulian Ointment and placebo. The codes were stored by the principle investigator and the third party, so in the event of severe adverse reaction, the randomization code and group allocation of the participant could be identified. Participants were assigned to receive Pulian Onitment or placebo in sequential fashion. All subjects and investigators who were also the outcome assessors were blind to the randomization sequence and treatment allocation until the completion of data analysis.Pulian ointment and placebo were produced and packaged by China-Japan Friendship Hospital.Huang Bai (Phellodendron amurense) powder 50 g, Huang Qin  powder 50 g, and white petroleum jelly 400 g. Pulian ointment was a prescription derived from Clinical Experiences of Bingnan Zhao, and often used to treat the following diseases: impetigo, acute and sub-acute eczema, scalds and burns, herpes simplex, psoriasis and erythroderma. Each box of Pulian ointment was 20 g.The ingredients of Pulian ointment include Huang Bai (Phellodendron amurense) and Huang Qin  purchased by the Department of Pharmacy of China-Japan Friendship Hospital were made into dusting powder, and screened through a 100–200 mesh sieve; white petroleum jelly was melted, filtered and cooled to a semisolid state; put the above dusting powders were added to the semisolid white petroleum jelly, stirred well, and continued to cool it until solidification. Quality of the Pulian ointment was tested and controlled by the Department of Pharmacy of China-Japan Friendship Hospital.The preparation of Pulian ointment was as follows: powdered Shen Qu (medicated leaven) was added to it. The quality of placebo was also tested and controlled by Department of Pharmacy of China-Japan Friendship Hospital. A test to distinguish Pulian ointment and the placebo was successfully conducted involving 10 healthy people, and 70% of the people tested could not distinguish between Pulian ointment and the placebo ointment.The Placebo ointment, 20 g per box, was prepared by same method of Pulian ointment. The matching placebo had similar smell and color with Pulian ointment because The Pulian ointment and placebo was applied externally, twice daily in the morning and at night after 12 h, continuously for 4 weeks. Specifically, the ointment was applied externally to all lesions on all areas of the body. The unit of dosage of the ointment was with the fingertip unit, which was the amount of ointment that fits on the space from the distal interphalangeal crease to the fingertip of the index finger of an adult. One fingertip unit of ointment was enough to be applied to an area of skin twice the size of the flat of one adult’s hand with the fingers together. The ointment was applied to an area 2 mm larger than the skin lesion area to ensure complete coverage. The method of application was to apply a sufficient amount in terms of ‘fingertip unit’, lightly pat the ointment on the lesion and spread it to form a thin ointment membrane over the skin lesion, then pat the areas for 1–2 min until the ointment was absorbed by the skin as much as possible.During the study, any other TCM, western medicines or other therapies for psoriasis were forbidden to use. If participants had any concomitant diseases, the corresponding medications or therapies should be continued to use. The name, dosage, frequency and duration of the medications or other therapies were recorded on the medical records of participants.All outcome measures were assessed and recorded at baseline, 2 weeks and 4 weeks. Follow-up assessments were scheduled at 4 weeks and 8 weeks after the end of treatment. Any adverse events were recorded throughout the study.  score: PASI is a quantitative rating score for measuring the severity of psoriatic lesions based on area coverage and plaque appearance.Severity of each symptom  and area of skin lesion was separately scored by PASI to compare the severity changes of each symptom of skin lesion after treatment between the two groups.Quality of life (QoL): Hamilton Anxiety Rating Scale (HAMA) and 36-Item Short Form Health Survey (SF-36) were used for the evaluation of QoL.Safety: any adverse events were recorded during the study. The indexes include vital signs, local skin responses, blood routine examination, urine routine examination, liver and kidney functions and other potential adverse reactions.All statistical procedures were performed with SAS 9.4 software and SPSS 17.0 software . Full analysis set (FAS) and Per protocol set (PPS) were applied for data analysis. FAS was defined as an analysis set as complete as possible including all randomized participants who had at least one time observation after randomization under Intention-to-treat (ITT) principles. If there was partially missing data, last-observation-carried-forward (LOCF) method was applied by replacing missing values with the last non-missing value. PPS was defined as a subset of the participants in the full analysis set who were more compliant with the protocol .P ≤ 0.05 was set as statistical significance. A one-tailed test was applied for the superiority test of the primary outcome measures. The effect size estimate and 95% confidence interval (CI) were presented for the results.Safety was evaluated by Safety Set (SS), which included those who received at least one dose of the investigational treatment and had data of safety assessment. A two-tailed test was applied for all hypothesis tests. Numerical (continuous) variables were analyzed by repeated measures analysis of variance (ANOVA), while categorical and ordinal variables by Cochran-Mantel-Haenszel test. The adherence of participants and incidence of adverse events were analyzed by chi-square test or Fisher’s exact test.Considering the variation in the assessment of PASI among the six centers due to the assessment being done by different investigators, Mixed Effect Model was used in this study to analyze the PASI scores and single characteristic scores of skin lesion so as to evaluate the changes from baseline, with baseline PASI score and therapeutic efficacy as Fixed Effect and centers as Random Effect.n = 149) or placebo group (n = 145). 34 participants dropped out the study, but 6 participants of Pulian ointment group and 7 participants of placebo group received treatment and completed one time point observation. Therefore, a total of 278 participants were in the ITT analysis, with 143 in the Pulian Ointment group and 135 in the placebo group; a total of 260 participants were included in per protocol analysis (PPS), with 132 in the Pulian ointment group and 128 in the placebo group. All participants who received at least one dose of Pulian Ointment or placebo were included in the safety analysis (SS)  , diastolic blood pressure (DBP), heart rate (HR), treatment history of psoriasis, skin lesion area, total SF-36 scores, HAMA scores, induration/thickness, area, erythema, scaling and PASI score (5) Table .Table 1BP = 0.043) and area of skin lesion  between Pulian ointment and placebo group (P < 0.05), but there was no difference between the two groups in scaling, erythema and induration/thickness scores analyzed with FAS (P > 0.05). In PPS, there was no statistically significant difference in PASI score and severity of each symptom and area of skin lesion between the Pulian ointment and placebo group (P > 0.05) , but the change scores were not statistically significant between the two groups both in FAS and PPS (P > 0.05). , but the change scores were not statistically significant between the two groups both in FAS and PPS (P > 0.05). .The adherence rate was 84 and 87.3% in the Pulian Ointment and placebo group, respectively. There was no statistically significant difference between the two groups in adherence rate  completed the follow up visits. 73 participants in placebo group were willing to be followed up, of which 71 (97.26%) completed the follow up visits.P > 0.05).In Pulian Ointment group, 5.88% (4/68) of participants who completed the follow up visits relapsed within 8 weeks, whereas in placebo group, 8.45% (6/71) of participants who completed the follow up visits relapsed within 8 weeks. There was no statistically significant difference between two groups in the relapse rate . However, no statistically significant difference was found between the two groups in PPS set. The underlying reasons might be as follows. Firstly, psoriasis vulgaris of blood-heat syndrome is characterized by the aggravation stage of psoriasis and the lesions are less stable, so there were natural variations in psoriasis among participants who are at different stages of exacerbation or remission during the treatment course of 4 weeks in this study. Secondly, the matrix of both the Pulian ointment and placebo ointment was white petroleum jelly, accounting 80% of the ointment. Previous studies showed that white petroleum jelly has some therapeutic effects on psoriasis [Quality of life after 4-week treatment in this study was improved within both groups measured by SF-36 and HAMA, however, Pulian ointment group was not superior to placebo group in the improvement of quality of life. This could be related to the placebo effect, short duration, and subjective measurement (questionnaires).During the 4 weeks of treatment in this study, no adverse events were observed in the Pulian ointment and placebo group, indicating the short-term safety of Pulian ointment in treating psoriasis vulgaris of blood-heat syndrome.Huang Bai (Phellodendron amurense), Huang Qin  and white petroleum jelly. Pharmacological studies demonstrated that Huang Bai (Phellodendron amurense) contains alkaloids , sterols  and limonins , which could inhibit proliferation and have antibacterial, anti-inflammatory and anticancer effects [Huang Qin  had anti-inflammatory, antioxidant, anticancer and immune-regulatory functions [Huang Qin  and its extract Baicalin in the treatment of psoriasis was the inhibition of the keratogenesis and cell proliferation [The potential mechanism of Pulian ointment in treating psoriasis vulgaris remains unclear. The ingredients of Pulian ointment include  effects . Choi YY effects  found thunctions . Currentferation , the actferation  and the feration . Yang WHferation  found thferation  revealedThere were some limitations of this study. Though all personnel had training courses and Manual for Investigators of this study were provided to the six centers, there were variations among different centers in recruitment, adherence and measurement. The recruitment in some study centers was more difficult than that of others. The possible reason might be that people are hesitated to use Pulian ointment due to the yellow ointment stains. Though the adherence rate of Pulian ointment group (84%) was acceptable, we recommend future research apply some methods to prevent staining of clothes, such as covering the area with a gauze dressing. In addition, the outcome assessor was not the same investigator in each study center, resulting in variations of measurement of PASI.Another issue is that 4-week treatment was too short to provide an assessment of the long-term efficacy and safety of Pulian ointment. Since psoriasis is a chronic, relapsing skin disease, the long-term effects of a medication will be an important concern of the patients with psoriasis. Future studies could consider longer treatment durations and follow-up periods.Furthermore, it is unclear from this study that whether other preparation form (such as a cream matrix or other formulation) or greater intervention intensity was necessary.Pulian ointment is potentially safe and effective in improving the PASI score and the separate score of skin lesion area for patients with psoriasis vulgaris of blood-heat syndrome. Further research could build on the current study by more closely exploring the preparation forms. Investigation of a possible dose–response relationship between Pulian ointment and PASI scores is also warranted in the future.Additional file 1: Table S1.Assessment procedures and time-points. (DOCX 14 kb)Additional file 2: Table S2.Table S3. Changes of HAMA scores from baseline in the Pulian ointment and placebo group. (DOCX 17 kb)Changes of SF-36 scores from baseline in Pulian ointment and placebo group.


In this paper, a tunable broadband metamaterial absorber (MA) based on graphene is investigated theoretically and numerically at mid-infrared regions. Compared with the previously reported multiband graphene-based MAs, a broad bandwidth of 11.7 THz with the absorption over 90% is obtained in the proposed MA, which is composed of a Jerusalem cross (JC) metal encrusting into the slot graphene layer in the top layer. The results show that the origin of broadband absorption is caused by coupling effect between metal and graphene, and this effect is explained by the two-mode waveguide coupling theory. The tunability of MA is achieved via changing the external gate voltage to modify the Fermi energy of graphene. Further results show that the proposed MA can be used as the permittivity sensor with a high absorption. This work indicates that the proposed MA has the potential applications with respect to sensors and infrared absorbers. The properties are used to realize some new physical functions like negative refraction index3, perfect lensing4, bolometers5, and PIT effect11, which are caused by sub-wavelength metallic resonators. Landy et al.12 demonstrated that the overall dimensions of MA can be designed to offer perfect absorption at microwave frequencies owing to the matched impedance to free space. Since then, lots of devices16 have been proposed and studied from the microwave17 to terahertz18 regions in order to obtain perfect absorption19, polarization-insensitive20, wide angle21 and tunability22. The single-band high absorption is unsuitable in practical applications23. Hence different methods have been proposed to induce a multi-band absorption, such as loading lumped elements24, introducing the asymmetric structure25, and using two circular rings with different radius26. Recently, using hybrid materials in the different layers is another way to realize the broadband or multiband absorption at THz regions. For example, Ling et al.27 designed a broadband polarization-insensitive MA based on hybrid materials  in the middle layer, which induces a high absorption from 60.5 to 115.5 THz. Zhou et al.28 reported a two-dimensional (2D) absorber using Si3N4 and Al, and exhibiting a perfect absorption over the whole visible region. However, these structures are suffered from some challenges as follows: (i) the tunability is obtained only by reconstructing the geometric structure, which is inappropriate for making the tunable devices30. (ii) The increased thickness is occurred when the hybrid materials are used to make broadband MA. Therefore a more straightforward and convenient strategy should be developed to guide the design of tunable MAs with a thinner thickness.Metamaterial absorbers (MAs), a new type of artificial materials, have been widely investigated in recent years due to the electromagnetic (EM) properties which are absent in traditional materials31: (i) its electric conductivity can be continuously tuned in a broad frequency range, (ii) the electrical tunability of graphene enables fast reflection or absorption modulation, (iii) graphene is a two-dimensional material, which makes it more suitable for planar structure, (iiii) graphene consists of one monolayer of carbon atoms, which means the thickness of the MA composed of graphene is thinner than that composed of the metal. Recently, lots of multi-band graphene-based MAs have been proposed35. However, a broadband high absorption is not obtained in the graphene-based devices.Graphene has attracted worldwide interests as a promising platform for building perfect tunable MAs due to its unique properties as followsIn this paper, a tunable graphene-based MA is proposed numerically and theoretically to realize the broadband absorption at mid-infrared regions. This absorber consists of three layers: a Jerusalem cross (JC) metal, which is embedded into the slot graphene plane at the top layer, a dielectric spacer, and the bottom gold film. The results show that a broad bandwidth of 11.7 THz with absorption over 90% is obtained due to the coupling effect between metal and graphene, and the origin of this effect is explained by using the two-mode waveguide coupling theory. The graphene’s Fermi energy can be dynamically tuned via changing the external gate voltage to realize the tunability of MA. Furthermore the proposed system has the advantage of high absorption for permittivity sensing application. Therefore this MA may find its potential applications in sensors and infrared absorbers.36. The third layer is metal plate, which is placed at the backside of dielectric layer and acting as an electrode for biasing the graphene layer as shown in Fig. σ = 4.09 × 107 S/m. The optimized parameters of the unit cell are listed as follows: p = 3 μm, w = 0.25 μm, g = 0.05 μm, l1 = 1.25 μm, l2 = 2.35 μm, t1 = t2 = t3 = 0.1 μm. Our results are obtained through a full wave EM simulation based on finite integration technique (FIT) and finite element method (FEM) owing to their accuracy in results and its suitability for the study of high frequency and three-dimensional EM structures39. In the x- and y- directions, the unit cell boundary conditions are utilized, and open space boundary conditions are applied in the z-direction. When the incident wave is vertical to the upper surface of the MA, the absorption A is obtained from the S-parameters by A = 1 − |S21|2 − |S11|2, where S11 is the reflection coefficient and S21 is the transmission coefficient. Due to the thickness of the gold is much larger than its skin depth, the transmission coefficient S21 = 0. Therefore the expression can be simplified as A = 1 − |S11|2.The unit cell of the MA is shown in Fig. 40:ω is the angular frequency, Ef is the Fermi energy of graphene, Γ is the collision angular frequency, T = 300 K is the temperature, Kb is the Boltzmann constant, e is the elementary charge, and ħ is the reduced Planck’s constant. When the Fermi level is larger than half of the photon energy, the intraband contributions dominate the graphene conductivity as the interband transitions are negligible due to Pauli blocking41. In this work, Ef is controlled by external gate voltage (Vg), and shown as following equation:vf = 106 m/s is Fermi velocity, εp is relative permittivity of spacer, ε0 is vacuum permittivity, Vg is external voltage. So the graphene’s surface conductivity is descried by the Drude model at infrared region42:μ = 20000 cm2 V−1 s−1. Then the relative permittivity of graphene can be written astg = 0.5 nm is the thickness of graphene film. According to the above equations, the different values of the permittivity of the graphene can be obtained.The complex surface conductivity of graphene (0.5 nm in thickness) can be calculated from the Kubo formula and is described with interband and intraband contributions asZt2 is the surface impedance of dielectric spacer. The top patterned metal array can be modelled by R-L-C circuit network. The resistance R and inductance L are induced by the metal, meanwhile capacitance C is caused by the gaps between the metal. But in the THz regime, the influence of R can be ignored. In Fig. Zg and Zm, respectively. The input surface impedance of dielectric spacer Z1 can be shown as follows:k0 and μ0 is vacuum permeability. Based on the effective medium theory43, the imaginary part of impedance must be equal to zero at the resonant point. So the corresponding reflection efficiency Γ is expressed byZ0 is the air impedance (≈377Ω) and Zg and metamaterial Zm should be solved. Thus the effective impedance Zm can be expressed as following40:n1 and n2 are the refractive indices of the air space and graphene layer. The sheet impedance of the graphene Zg can be expressed as:According to the transmission line theory, an equivalent circuit model (ECM) is presented in Fig. 44 is accurate in the proposed MA. We see that there is also a good spectral overlap between the FIT and FEM simulation curves, which can further confirm the validity of our numerical results. The absorption curves of three comparison absorber are shown in black line , red line  and blue line  in Fig. Zm) and dielectric spacer (Z1) are considered as a whole and shown by Zm1. Under this assumption, the expression of total input impedance (Zin) can be changed as follows:Figure Z = Zin/Z0) is shown in Fig. Z) = 1), and the imaginary part comes to zero (Im(Z) = 0) at the resonant points f1 = 84.2 THz and f2 = 91.2 GHz. Therefore at these two resonance points, the total input impedance of the MA (Zin) is matched to the air impedance (Z0), and results in the high absorption in the absorber, while the real and imaginary parts fluctuate intensively in the frequency range of 105.9 to 130.0 THz, and yielding a relatively low absorption coefficient.The relative impedance of the proposed MA  and 2 (graphene). Ca = Cb and Kab = Kba = K. Based on this assumption, the power (P) of EM wave through the MA can be given by the following equations:k ≫ K, the power can be exchanged between waveguide 1 and 2, it means that the interference effect between these two waveguides has taken place in the system, which is also seen in Fig. The classical “two-mode waveguide coupling” model is used to explain the coupling effect. Based on the above discussion, the metal and graphene can be modeled as two waveguides, and satisfy the following coupled equationsμ of the graphene layer is investigated because it is susceptible to the interface problem. Figure μ is, the lower intrinsic quality factor is46. Figure Zg with different Fermi Level Ef, respectively. It is found that the imaginary part of the Zg continuously decreases with Ef increases and the real part of Zg keeps constant when the frequency increases.Figure 47σg(ω) is the conductivity of graphene, S is the area of graphene, Exy is the electric field in the plane of graphene, W0 is the stored electromagnetic energy in an uncovered metamaterial resonator. Re and Im represent real and imaginary part of a complex value, respectively. From equation (ω is determined by Im(σg(ω)), whereas the amplitude modulation of the resonance peak is determined by the losses in graphene given by Re(σg(ω)). At the infrared region, by manipulating graphene’s Fermi energy, it is possible to continuously adjust the absorption peaks and achieve the tunability of the MA.When graphene is placed in the vicinity of a metamaterial resonator, it will perturb the resonator. The change of the resonant angular frequency is given by48. In Fig. ε) varying from two to ten is placed onto the surface of graphene layer to fulfill this criterion. The corresponding absorption curves are shown in Fig. Generally the sensitivity of permittivity sensors depends critically on the fact that the variation of permittivity of analyte medium can bring about the change in position of the 80% absorption point48 and49. The differences are summarized as follows: Firstly, the absorption efficiency of Fano-resonant metamaterials for the plasmonics-induced transparency (PIT) application is low, which limits the possibility of high absorption in MA, while the proposed structure is achieved and maintained this by using the tri-layer graphene-based MA. Secondly, the PIT is formed when the asymmetric structure is introduced into the system, while the proposed MA is a symmetric structure, which is simpler in experimental design. Thirdly, although the Fano-resonant graphene-based metamaterials have much higher qualify factor, the proposed system obtains the broadband high absorption and can be used to meet the requirement of perfect absorption in PIT devices.We give a systematic comparison with the previous reported results in refsIn summary, a tunable broadband graphene-based MA has been proposed numerically and theoretically at mid-infrared regions. Compared with the previously reported multiband graphene-based MAs, the proposed MA can obtain a broadband high absorption in the range of 82.3 to 94.0 THz via embedding JC metal into slot graphene layer, which is caused by the coupling effect between the metal and graphene, and this coupling effect is explained by two-mode waveguide coupling theory. The tunability of MA is obtained by manipulating the Fermi energy of the graphene layer through controlling external gate voltage instead of re-constructing the geometric structure. The ECM, distributions of electric field, surface current and power loss density are applied to explain the absorption mechanism. Further results show that the proposed MA can be used as a permittivity sensor. Therefore the proposed MA can find its potential applications in sensors and infrared absorbers.


Background: The evidence of increased mortality attributable to extreme temperatures is widely characterized in climate-health studies. However, few of these studies have examined the role of humidity on temperature-mortality association. We investigated the joint effect between temperature and humidity on cardiovascular disease (CVD) mortality in Zhejiang Province, China. Methods: We collected data on daily meteorological and CVD mortality from 11 cities in Zhejiang Province during 2010–2013. We first applied time-series Poisson regression analysis within the framework of distributed lag non-linear models to estimate the city-specific effect of temperature and humidity on CVD mortality, after controlling for temporal trends and potential confounding variables. We then applied a multivariate meta-analytical model to pool the effect estimates in the 11 cities to generate an overall provincial estimate. The joint effects between them were calculated by the attributable fraction (AF). The analyses were further stratified by gender, age group, education level, and location of cities. Results: In total, 120,544 CVD deaths were recorded in this study. The mean values of temperature and humidity were 17.6 °C and 72.3%. The joint effect between low temperature and high humidity had the greatest impact on the CVD death burden over a lag of 0–21 days with a significant AF of 31.36% (95% eCI: 14.79–38.41%), while in a condition of low temperature and low humidity with a significant AF of 16.74% . The AFs were higher at low temperature and high humidity in different subgroups. When considering the levels of humidity, the AFs were significant at low temperature and high humidity for males, youth, those with a low level of education, and coastal area people. Conclusions: The combination of low temperature and high humidity had the greatest impact on the CVD death burden in Zhejiang Province. This evidence has important implications for developing CVD interventions. Environmental risk factors have emerged as a major public health concern, with a growing literature investigating the effects of weather variations on human health. Previous literature has found cardiovascular disease (CVD) is most sensitive to weather across various climates throughout the world . Fueled The Intergovernmental Panel on Climate Change (IPCC) has stated that an increase in extreme weather is the result of climatic change, and one of the greatest challenges we face today worldwide . NumerouCurrently, most studies rely on summaries based on relative risk (RR), odds ratio (OR), and rate ratio, resulting in limited information on excess burden due to volatile weather exposure. The attributable fraction (AF) and attributable number (AN) may solve these problems and could provide the accumulative effect from a specified time period and present the fraction of cases or deaths from a disease . Those iIn this study, we aimed to fill gaps in current knowledge by identifying the effect of relative humidity on the relationship between temperature and CVD mortality. We also identified vulnerable groups and provided more evidence for policymakers to develop public health interventions to reduce the risk effect of CVD mortality.2 and a population size of 55.9 million in 2016. There are four distinct seasons and overall pleasant climate. The annual mean temperature ranges from 15.0 to 18.0 °C, and the average annual rainfall is 980 to 2000 mm across cities. We collected daily mortality and meteorological data from 11 cities in Zhejiang Province, China. In total, there were seven coastal cities  and four inland cities . Zhejiang Province is located in the southern part of the Yangtze River Delta on the east coast of China with a total land area of 105,500 kmThe daily count of death data was acquired from the Zhejiang Provincial Center for Disease Control and Prevention during the period 2010 to 2013. The original data included variables on age, sex, education, date of mortality, and cause of death. CVD was based on primary death cause and was categorized by the International Classification of Diseases, Tenth Revision (ICD-10): I00-I99. We conducted stratified analyses by sex, age group (0–74 years and 75+ years), education levels , location of cities , and levels of humidity . http://cdc.nmic.cn/home.do). The observation station in each city included daily maximum, minimum, and mean degrees of temperature, relative humidity, wind speed, and atmospheric pressure. The data did not contain any missing values during the study period. Previous studies have documented that atmospheric pressure and wind speed are important risk factors for death. In particular, these two variables may have an influence on humidity [We collected meteorological data from China Meteorological Data Sharing Service System  natural cubic smooth function with 7 degrees of freedom (df) per year to control long-term and seasonal trends; (2) 3 df was used for relative humidity, atmospheric pressure, and wind speed, respectively; (3) days of the week and public holidays were analyzed as categorical variables. Specifically, we modeled the exposure-response curve with a quadratic B-spline with three internal knots placed at the 10th, 75th, and 90th percentiles and the lag-response curve with a natural cubic B-spline with three internal knots placed at equally spaced values in the log scale with maximum lag of 21 days ,20. The For the modifying effect of humidity, we calculated the cold and hot effects on CVD mortality in the stratified analyses by low and high humidity. The minimum mortality temperature (MMT) was used as a reference for calculating the relative risk by re-centering the models. The city-specific cumulative relative risk over lag periods was used to compute the daily attributable death (AD) corresponding to each day’s temperature. The ADs of different levels of humidity were calculated by aggregating the humidity level contributions from the days of the series, and their ratio to the corresponding total number of deaths yielded low or high humidity attributable fraction (AF) . Low andQ test and I2 statistic to evaluate the heterogeneity of 11 cities. To identify vulnerable subpopulations, we conducted subgroup analyses based on gender, age, education level, and location of cities. In the second stage analysis, we used multivariate meta-analytical model to pool the city-specific effect estimates. We reported both Cochran The sensitivity analyses were performed to check the robustness of the results. We changed the knots of temperature-mortality dimension, the maximum lag days for mean temperature from 14 to 24, and different degrees of freedom per year for time trends from 6 to 10. The df of weather variables such as relative humidity, atmospheric pressure, and wind speed, is from 4 to 6, respectively. All the model choices were performed by Q-AIC. p-values < 0.05 were considered statistically significant.All analyses were performed using R software  by using DLNM and MVMETA packages to fit the two-stage model. All statistical tests were two-tailed, and Q = 48.72, I2 = 17.9%, p = 0.162). The daily mean temperature ranged from −2.7 to 35.7 °C and relative humidity ranged from 17 to 100% in the 11 cities. The median temperature and relative humidity were 18.4 °C and 73%.p < 0.05), and mean temperature and relative humidity . However, we found negative correlations between daily CVD death and daily mean temperature . Additionally, the correlations between daily CVD deaths and atmospheric pressure, as well as daily CVD deaths and wind speed, were both significant in this study.We conducted sensitivity analyses on modeling choices. The effect estimates for total AFs and QAIC were similar when changing the location of knots for the exposure-lag-response relationship and the degrees of freedom for time and meteorological factors . The tesTo the best of our knowledge, this is the first study to examine whether humidity modifies the association between temperature and CVD mortality in Zhejiang Province, China. The main finding on the joint effects was that low temperature and high humidity could account for majority of CVD death burden, with an AF of 31.36%, and with a significant AF of 16.74% in the condition of low temperature and low humidity. Recently, Gasparrini et al. reported a similar study estimate of 11.3% for all-cause mortality was attributed to ambient temperatures in China, which is smaller than our estimates . A studyp < 0.05), and a negative correlation between daily CVD death and daily mean temperature . Similarly, previous studies also found a positive relationship between relative humidity and CVD death, and a positive relationship between temperature and CVD death [Our study showed the impact of temperature on CVD death was higher at high humidity. High humidity may lead to increased thrombotic risk , exacerbVD death ,24. HoweVD death ,25. In gEpidemiological studies have verified that susceptibility to extreme weather varies by gender and age ,27,28. OOur study found youths and the elderly had higher risk at low temperatures and high humidity, with an AF of 32.50% and 27.86%. The CVD death burden was significant and higher among youth when compared to the elderly. Perhaps elderly people are more likely to remain at home and are therefore not exposed to cold temperatures frequently. Moreover, age-appropriate primary care and community-based measures have been targeted for the elderly. In recent years, the proportion of younger men of the total number of employees in industry, construction, and agriculture has been relatively stable in Zhejiang Province, China. Younger people often work outside, resulting in elevated exposure to cold temperatures ,31,32. SPoverty is associated with a greater risk of cardiovascular disease, as well as lower levels of education, a major determinant of disease and death in low-income countries . Low eduOur study revealed that specific location was associated with cold-related and humid-related deaths. In coastal areas, high temperature and high humidity were associated with higher and more significant risks, with an AF of 27.25% for CVD death. However, we did not observe significant association between joint effect of temperature and humidity on CVD mortality for inland areas. A possible explanation is the air in coastal areas often contains more moisture than inland areas. Majority of residents lived in coastal areas, which resulted in a greater impact on CVD mortality compared with those in inland areas. The frequently adverse weather conditions may cause larger accumulative harmful health impacts to local residents.Although the mechanism on how humidity affects health remains unclear, it is biologically plausible that the effects of extreme temperature on the cardiovascular system may be involved in the changes in vascular tone, autonomic nervous system response, arrhythmia, and oxidative stress. Cold exposure may raise a number of thrombogenic factors, such as blood cell counts, plasma cholesterol, C-reactive protein, fibrinogen concentrations, and platelet reactivity. It could also increase the frequency of heart rate and ventricular ectopic beats, and may contribute to morbidity and mortality in sympathetic nervous system and the hemodynamic system when responding to cold stress . MeanwhiThe present study makes a number of contributions, as follows: To the best of our knowledge, this is the first study to provide comprehensive evidence that the joint effect of temperature and humidity is an important factor in CVD mortality in China. Specifically, majority of previous studies were based on relative risk and other diseases, and did not consider the integrated effects of temperature and humidity on CVD mortality ,43. FurtOur present study also has limitations. First, data were only from 11 cities in Zhejiang province. For this reason, it is important to be cautious when extending our findings to other areas in China because of the unique weather conditions and other city-specific parameters. Second, measurement errors with temperature and humidity are inevitable and the collected data from monitoring stations may not best reflect real exposure level, especially for those persons who died far from the station. Third, we have only considered the deaths where CVD was the underlying cause. To provide greater knowledge, we would need to separately investigate people with and without preexisting CVD. Fourth, the data on air pollution were unavailable, and unmeasured residual factors such as smoking, family history of CVD, air condition use, and activity patterns may potentially confound the relationship.The significantly influential study should play an important role in public health policy implications. First, our findings suggest identified susceptible subpopulations that should be specifically targeted. Second, our analysis found that humidity is a modifier in southern areas on human health that can be extended to other areas in further studies. Third, this study could encourage health care institutions and governmental agencies to establish a fair policy on climate change adaptation. Our study found that humidity might be an important factor to modify the relationship between temperature and mortality in Zhejiang, China. This was also observable for the joint effect between low temperature and high humidity, having the greatest influence on CVD death burden, in which the effect was significant and stable at different lag periods. At different levels of humidity, the AFs were highest at low temperature and high humidity in stratified analyses by gender, age group, education level, and location of cities. In addition, the effects were significant for males, youth, those with a low level of education, and individuals in coastal areas. These identified, susceptible subpopulations should be specifically protected. Evidence from our study is complementary to the literature and has important public health implications for planning intervention measures to reduce CVD mortality risk. Further research needs to be verified and extended to other areas.