N,N′-bis(3-aminopropyl)ethylenediamine) and 4A-3P -1,3-propanediamine) crosslinked with terephthaloyl chloride (TPC) on a crosslinked polyacryonitrile (PAN) support through interfacial polymerization (IP). The presence of multiple hydrophobic –CH2– groups in the structures of the aliphatic amines 4A and 4A-3P develops hydrophobic sites in the hydrophilic polyamide active layers of the membranes. In addition, 4A has two secondary amino groups separated by ethylene (–CH2–CH2–) groups, whereas in 4A-3P, the two secondary amino groups are separated by propylene (–CH2–CH2–CH2–) leading to variation in the structural features and performance of the two membranes. Both membranes were fully characterized by several membrane characterization techniques and applied for OSN/SRNF using both polar  and non-polar (n-hexane and toluene) solvents. Different dyes  were used as model solutes during the filtration experiment. The 4A-3P-TPC@crosslinked PAN showed n-hexane and toluene flux of 109.9 LMH and 95.5 LMH, respectively. The Congo red (CR) showed the highest rejection, reaching 99.1% for the 4A-TPC@Crosslinked PAN membrane and 98.8% for the 4A-3P-TPC@Crosslinked PAN membrane.Given the huge significance of organic solvents in several industrial processes, the use of membranes for recovering the solvents has evolved into an industrially viable process. The current work has been focused on studying the effect of minor changes in the chemistry of the reacting monomers on the organic solvent nanofiltration/solvent resistance nanofiltration (OSN/SRNF) performance of the membranes. The two aliphatic amines with varying aliphatic chain lengths between primary and secondary amines were selected for this purpose. Based on the structure of the resultant active layer, the Janus nanofiltration performance of the membrane was evaluated. The two membranes, 4A-TPC@crosslinked PAN and 4A-3P@crosslinked PAN were fabricated by using two different tetra-amines, 4A ( Hence, the chemical industries are constantly improving their processes to (i) meet the stringent environmental regulations and (ii) increase their profit2. Among the chemical industries, the pharmaceutical industries are heavily dependent on the consumption of organic solvents, where organic solvents account for 80–90% of the total mass in the process3. The most common solvent wastes generated by pharmaceutical companies include methanol, dichloromethane, toluene, acetonitrile, and chloroform. Among the different organic solvent wastes, methanol waste has been estimated to reach 44.8 × 106 kg per year. Compared to conventional processes such as distillation and adsorption, membrane-based separations are less energy intensive, eco-friendly, have a footprint, cost-effective for product isolation and concentration4.Organic solvents are of prime significance in several industrial processes, ranging from pharmaceuticals to petrochemicals. The reuse of highly precious organic solvents is of utmost economic significance as it can lower the demand for fresh organic solvents7, which is due to certain salient features of the TFC membranes such as chemical and physical stability, adaptability to different feed compositions, and easy availability with a wide range of pore sizes for a desired application10. TFC membranes consist of a thin selective layer deposited on top of a porous polymeric ultrafiltration support. Generally, the porous polymeric ultrafiltration support is prepared through wet phase inversion by using water as a non-solvent in the process. On the other hand, the active layer is grown on the ultrafiltration support through interfacial polymerization (IP)11. Given the versatility of the IP process, a huge variety of TFC membranes have been fabricated in the literature by either altering the chemistry of reacting monomers or changing the other parameters of IP12.With the development of thin film composite (TFC) membranes, several separation processes have been optimized13. Another group reported the green synthesis of a PA TFC membrane by using polyethylenimine (PEI) as an amine solution cross-linked with TMC on porous PAN support. The IP reaction was carried out using decanoic acid as the organic phase. The membrane was able to reject the majority of the tested dyes with a molecular weight cut-off (MWCO) of 650 g mol−114. Recently, molecule-based design strategies have been explored by the research community for manipulating the pore structure and physicochemical properties of organic solvent nanofiltration/solvent-resistant nanofiltration (OSN/SRNF)15 membranes. In a recent study by Alduraiei et al., fluorine-containing diamine, 5-trifluoromethyl-1,3-phynelenediamine (TFMPD), was crosslinked with TMC and 4,4′-(hexafluoroisopropylidene)bis(benzoyl chloride) (HFBC) during IP. Since the presence of fluorine atoms in the active layer gives a hydrophobic feature to the membrane, the resulting membranes were used for cleaning non-polar solvents. The TFMPD-HFBC membrane showed a toluene permeance of 10 L m−2 h−1 bar−116. Thijs et al. used a novel approach to tune the chemistry of the active layer of the TFC membrane by growing an active layer consisting of polymers of intrinsic microporosity (PIMs). In their work, several amine monomers with 2.5–4 amines per molecule were crosslinked with binaphthalene-based di(acid chloride) through IP on Matrimid support. The fabricated membrane showed an increase in acetonitrile permeance by a factor of 20 compared to a conventional MPD/TMC membrane. By comparing the structure and performance of the different fabricated membranes, the team found that changing the number of amine groups per molecule and altering the length of alkyl chains on binaphthalene-based di(acid chloride) altered the performance of the membranes17. In one such instance, Liu et al. constructed Janus pathways by using cyclodextrin (CD) in the membrane. The presence of CD in the constructed OSN/SRNF membrane allowed passage of both polar and non-polar solvents, which is attributed to the inner hydrophobic cavities and outer hydrophilic spaces of CD18. However, the larger pore size of CD lowers the rejection of the membrane. Similarly, Li et al. developed a Janus membrane by using β-cyclodextrin (BCD) as a monomer during IP on a polyelectrolytes-based interlayer developed through layer-by-layer self-assembly. The membrane was able to permeate both polar and non-polar solvents with permeances reaching 5.8 LMH/bar for methanol and 7.0 LMH/bar for hexane along with a 91.9% rejection of methyl orange19. In another work, Li et al. used m-xylylene diamine (m-XDA) as an aqueous monomer crosslinked with TMC leading to a Janus membrane for the passage of both polar and non-polar solvents. The addition of an additional methylene –CH2– group in m-XDA rendered the hydrophobic features to the hydrophilic polyamide active layer of the membrane20. Hence, minor variations at the molecular level of reacting monomers lead to different structural features targeting a specific application. Therefore, the need of the day is to come up with new membranes with structural, physical and chemical stability by tuning the chemistry of reacting monomers.The variations in the chemistry of the active layers of TFC membranes have led to remarkable applications. Solomon et al. reported a polyamide (PA) TFC membrane by using conventional meta-phenylenediamine (MPD) as an aqueous monomer and trimesoyl chloride (TMC) as a non-aqueous monomer during IP. The membrane was prepared on a polyimide (PI) substrate and showed solvent resistance2– groups in the structure of tetra-amines (4A and 4A-3P) introduced several hydrophobic sites inside the hydrophilic polyamide active layer leading to the passage of both polar  and non-polar (n-hexane and toluene) solvents. Moreover, another variation in the chemistry of the newly developed polyamide active layer was also introduced as in the case of 4A both primary (–NH2) and secondary (–NH) amines were separated by ethylene –CH2–CH2– groups. In the case of 4A-3P, the two primary (–NH2) amino groups are separated by ethylene –CH2–CH2– and the two secondary amino (–NH) groups are separated by propylene –CH2–CH2–CH2– chain. This variation at the molecular level could potentially lead to different morphological and structural features leading to varied OSN performance. The fabricated membranes were extensively characterized by using a scanning electron microscope (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, water contact angle (WCA), atomic force microscopy (AFM), energy dispersive X-ray (EDX) and elemental mapping. The fabricated membranes were used for OSN/SRNF applications by using both polar and non-polar solvents while different dyes were used as model solutes during filtration experiments.The current study was carried out by using the linear aliphatic amines 4A-3P and 4A on a crosslinked PAN support. The study was carried out through interfacial polymerization between either 4A-3P and TPC or 4A and TPC on crosslinked PAN support. In comparison to the previous studies where cyclic amines such as piperazine or aromatic amines such as meta-phenylenediamine (MPD) were used, we have used linear aliphatic amines 4A and 4A-3P crosslinked with an organic phase containing terephthaloyl chloride (TPC) as a cross-linker. The presence of multiple methylene –CHN,N′-Bis(2-aminoethyl)-1,3-propanediamine , N,N′-bis(3-aminopropyl)ethylenediamine , Triethylamine , Polyacrylonitrile , n-Hexane (≥ 99%), N,N′-dimethyl formamide , Polyethylene Terephthalate (PET) fabric, Methylene blue , Eriochrome black T , and Congo red  were all purchased from Sigma . Deionized (DI) water from the in-lab setup was used for all the experiments.Terephthaloyl chloride , 2–NH2) aqueous solution at 70 °C for 6 h. Then the crosslinked PAN support was thoroughly washed with an excess of DI water.The PAN dope solution was prepared by dissolving 12 g of perfectly dried PAN in 88 g of DMF. The solution was stirred at room temperature overnight, leading to a transparent solution of PAN. The PAN dope solution was allowed to stand until all of the air bubbles were completely removed. The PAN support was prepared by spreading an appropriate amount of PAN dope solution on a PET sheet affixed to a glass plate. Then the PAN was cast by using a custom-made Doctor’s blade (100 µm slit width) on PET support. Immediately after casting PAN, the support was dipped in a deionized water bath and allowed to stand, leading to phase inversion. Hence, PAN/PET ultrafiltration support was fabricated. The PAN support was crosslinked by dipping an appropriate piece of PAN/PET support in a 25% (v/v) hydrazine  −1, this can be attributed to the stretching vibration of the N–H bond of the amide linkage (–CO–NH) of the polyamide active layer of 4A-TPC@Crosslinked PAN and 4A-3P-TPC@crosslinked PAN. Similarly, in the case of crosslinked PAN, the 3600–3200 cm−1 broad peak can be attributed to the existence of the –N–H bond generated during crosslinking using hydrazine (NH2–NH2) as a crosslinking agent. As we move further, there is a short but relatively sharp peak located at 2900–2800 cm−1 in all of the FTIR spectra of all membranes including crosslinked PAN. This characteristic peak is due to –C–H stretching of the aliphatic backbones of the polyamide active layer due to constituent amines 4A, 4A-3P and PAN support. Furthermore, a very sharp and deep peak was visible at around 2200 cm−1 which is due to residual nitrile (–C≡N) groups in PAN. A relatively medium peak of crosslinked PAN can be seen in the region of 1700–1650 cm−1 which can be attributed to the stretching vibration of C=C/C=N bonds that originated during the crosslinking event of PAN with hydrazine. However, in the case of 4A-TPC@crosslinked PAN and 4A-3P-TPC@crosslinked PAN membranes, a doublet peak is shown in the region of 1700–1600 cm−1. In addition to C=C/C=N bonds of PAN, 4A-TPC@Crosslinked PAN and 4A-3P-TPC@Crosslinked PAN membranes have carbonyl functional group (> C=O) of the primary/secondary amide linkages of polyamide active layers. The doublet in the region of 1700–1600 cm−1 is attributed to the C=C/C=N and > C=O bonds of PAN and polyamide active layers. Therefore, the ATR-FTIR spectra of crosslinked PAN, 4A-TPC@Crosslinked PAN and 4A-3P-TPC@Crosslinked PAN membranes have confirmed the presence of all the functional groups and bonds in their structure  analysis as shown in Fig. The elemental mapping analysis revealed a uniform distribution of all the elements throughout the entire membrane Fig. .Figure 72) are ethyl chains. This particular structure of 4A-3P allows flexibility of binding of TPC with the neighbouring 4A-3P chains. However, in the case of 4A amine, the secondary amino groups (–NH–) are separated by ethyl chains and primary amino groups (–NH2) are separated by propyl chains. As the secondary amino groups are close together the incorporation of TPC in between is not flexible and uniform . It was observed that the WCA of the Hydrazine Crosslinked PAN support was found to be 45.9° and hence the crosslinked PAN support was considerably hydrophilic. The hydrophilicity of crosslinked PAN support can be attributed to the contribution of hydrazine introducing amino groups in the support. Furthermore, the hydrophilicity of crosslinked PAN can also be due to partial hydrolysis of the PAN support. However, after the growth of the polyamide active layer on crosslinked PAN support, the membrane surface hydrophilicity decreased as the WCA increased (65.1°) in the case of 4A-TPC@Crosslinked PAN membrane and 59.9° for 4A-3P-TPC@Crosslinked PAN Fig. . This mia) and root mean square roughness (Rq) were found to increase in the following order: crosslinked PAN > 4A-TPC@Crosslinked PAN membrane > 4A-3P-TPC@Crosslinked PAN membrane  of 4A-3P-TPC@Crosslinked PAN membrane was higher (12.8 nm) than 4A-TPC@Crosslinked PAN membrane. The higher Ra values in the case of 4A-3P-TPC@Crosslinked PAN membrane were attributed to the presence of large valleys and deep ridges as seen in Fig. Another salient feature of membranes is their surface roughness which was measured by recording atomic force microscopy (AFM) images of the crosslinked PAN, 4A-TPC@Crosslinked PAN membrane and 4A-3P-TPC@Crosslinked PAN membrane. The membrane average roughness  showed the highest permeate flux, reaching 80 LMH, while isopropanol possessed the lowest permeate flux of 3 LMH and had the highest viscosity of 1.92 cP.The variation in permeate flux can also be explained by considering another factor, which is the viscosity of the solvent. It has been observed that as the viscosity of the solvent increases, the permeate flux decreases in an inverse pattern. The inverse relationship between viscosity and permeate flux can be seen in Fig. The separation potential of OSN/SRNF membranes was also studied by using different dyes such as CR, EBT, and MB as model solutes. The solution of each dye was prepared by dissolving an appropriate amount of the dye in methanol at a concentration of 10 ppm. The feed of each dye was loaded in the dead-end cell and filtration was carried out at 4 bar. The flux of both membranes remained constant for all of the tested dyes Fig. a,b. DuriFigure The OSN/SRNF performances of the current membranes have been compared with those of similar membranes from the literature as given in Table −2 h−1 as the pressure was increased from 4 to 10 bar. The 4A-3P-TPC@Crosslinked PAN membrane possessed n-hexane and toluene flux of 109.9 and 95.5 L m−2 h−1 respectively. The Congo red showed the highest rejection reaching 99.1% for 4A-TPC@Crosslinked PAN membrane and 98.8% for the 4A-3P-TPC@Crosslinked PAN membrane. In the case of Eriochrome Black T, the rejection stayed at 99.1% for 4A-TPC@Crosslinked PAN membrane while it was slightly reduced for 4A-3P-TPC@Crosslinked PAN membrane reaching 94.4%. Based on the rejection and flux data, the ethylene moeity between the two secondary amines led to a denser active layer compared to the propylene chain between the secondary amine groups of aliphatic amines.Interfacial polymerization has been successfully utilized for the fabrication of two thin film composite organic solvent nanofiltration/solvent resistant nanofiltration membranes. The structure of the polyamide active layers was tuned by slightly altering the chemistry of the reacting amines. Two different linear aliphatic amines, 4A with ethylene and 4A-3P with propylene, were used as aqueous amine solutions during IP on crosslinked PAN support. The resultant organic solvent nanofiltration/solvent resistant nanofiltration membranes 4A-TPC@Crosslinked PAN and 4A-3P-TPC@Crosslinked PAN membranes, were thoroughly characterized through scanning electron microscopy, water contact angle, energy disperse X-ray analysis, elemental mapping, attenuated total reflectance Fourier transform infrared spectrometry and atomic force microscopy. During organic solvent nanofiltration experiments, the 4A-TPC@Crosslinked PAN membrane showed an increase in permeate flux of n-hexane and toulene from 33.8 to 81.1 L mSupplementary Figures.


The search for highly efficient adsorbent materials remains a significant requirement in the field of adsorption for wastewater treatment. Computational study can highly contribute to the identification of efficient material. In this work, we propose a computational approach to study the adsorption of four cationic basic dyes, basic blue 26 (BB26), basic green 1 (BG1), basic yellow 2 (BY2), and basic red 1 (BR1), onto two models of graphene oxide as adsorbents. The main objectives of this study are the assessment of the adsorption capacity of the graphene oxide towards basic dyes and the evaluation of the environmental and temperature effects on the adsorption capacity. Quantum theory of atoms in molecules (QTAIM) analysis has been used to understand the interactions between the dyes and graphene oxides. In addition, adsorption free energies of the dyes onto graphene oxides are calculated in gas and solvent phases for temperatures varying from 200 to 400 K. As a result, the adsorption free energy varies linearly depending on the temperature, highlighting the importance of temperature effects in the adsorption processes. Furthermore, the results indicate that the environment (through the solvation) considerably affects the calculated adsorption free energies. Overall, the results show that the two models of graphene oxide used in this work are efficient for removing dyes from wastewater.We have optimized the complexes formed by the interaction of dyes with graphene oxides at the PW6B95-D3/def2-SVP level of theory. The SMD solvation model realizes the implicit solvation, and water is used as the solvent. Calculations are performed using the Gaussian 16 suite of program. QTAIM analysis is performed using the AIMAll program. Gibbs free energies as function of temperature are calculated using the TEMPO program.The online version contains supplementary material available at 10.1007/s00894-023-05761-8. Organic compounds, dyes, antioxidants, and pharmaceutical and personal care products are the primary pollutants that cause directly and indirectly damage and threaten human health. Emerging dyes are used in many sectors, such as textile sorting, printing, dyeing, and plastic production of plastics . HoweverPrevious work highlights the importance of the adsorption of basic dyes and provides avenues for developing new water treatment methods to eliminate emerging pollutants. Regti et al.  studied Using molecular dynamic simulations, the adsorption of dyes onto models of graphene oxide has been reported by several authors in the literature –18. Adsoa et al.  performea et al. .The exploration of the literature shows that few of the theoretical works have been reported. The search for efficient adsorbent materials remains a significant requirement in the field of adsorption for wastewater treatment. Most of the calculations in the literature are reported using electronic energy. It is necessary to use the Gibbs free energy to evaluate the adsorption process. The Gibbs free energy of adsorption considers the entropic and temperature effects on the adsorption. Despite some studies on implicit solvation, most research is carried out without considering the solvent effects on adsorption energy. In the present study, we studied the adsorption of four cationic basic dyes, BB26, BG1, BY2, and BR1, onto two models of graphene oxide as adsorbents. Calculations are performed in the gas and solvent phase using the PW6B95-D3  functionThis section starts with the presentation of the two models of graphene oxide used in this work  or even dyes of the same class, but which differ in their chemical structures. Graphene oxide (GO) has a structure similar to that of graphene. These two materials have a hexagonal carbon lattice, but the GO sheet is usually distorted where it is bound to oxygen groups . The resment}sp2 . The funment}sp2  and offementclass2pt{minimEA) and the ionization potential (IP) are calculated using Eqs. Chemical quantum molecular descriptors of the studied dyes have been calculated in this work to understand their reactivity. These descriptors are calculated using the frontier molecular orbitals HOMO  and LUMO . The energy gap values HOMO-LUMO (mentclass2pt{minimThe free energies of the complexes (dye + GO) at different temperatures are calculated using Fifen and coworkers’ TEMPO program , 25. TheIn this section, we comprehensively describe the computational approach used to study the adsorption of dyes  onto two models of graphene oxide as adsorbents. The adsorption is studied in both the gas phase and implicit solvent phase. Molecular structures of the dyes were built using the Avogadro . The theA QTAIM analysis is performed on the complexes to study the interactions between the dyes and the graphene oxides. The AIMAll program performs the QTAIM analysis .For the sake of the completeness of the study, the investigation started with calculating some DFT-based descriptors of the dyes to understand their reactivity. These calculations exploit the frontier molecular orbital energies. After calculating the descriptors, the structures of the complexes formed by the dyes and the two models of graphene oxide are optimized at the PW6B95-D3/def2-SVP level of theory. To understand the interaction between the dyes and the GO models, QTAIM analysis of the eight complexes is performed. Using the optimized structures of the complexes, the adsorption electronic energies and the adsorption free energies at room temperature are calculated. Finally, the effects of the temperature on the adsorption free energies of the complexes are assessed and presented.Molecular electronic descriptors and their calculated values are shown in Table The values of the electrophilicity index (mentclass2pt{minimacceptor . A stronument}ω) . The stamentclass2pt{minimTo calculate the adsorption energy, one needs the structures of the complexes formed by the combination of a dye and a GO model, in addition to the individual structures of the GO models and the dyes. Thus, we formed eight complexes by combining the GO models and the four dyes. After optimizations of the structures at the PW6B95-D3/def2-SVP level of theory, the located stable configurations are reported in Fig. To understand the interactions between the graphene oxide and the dyes, we performed a QTAIM analysis of the eight complexes. The structures reported in Fig.  bonding , 44. In  bonding –52. ThusAnalysis of Fig. Using the structures reported in Fig. For the first model of graphene oxide, the free energy values at room temperature are BB26  onto two models of graphene oxide at the PW6B95-D3/def2-SVP level of theory. We started by calculating some DFT-based descriptors of the dyes to predict their reactivities based on the frontier molecular orbital energies. Then, a QTAIM analysis has been performed. This allowed us to understand the interactions between the dyes and the graphene oxides. It has been found that the CHConformational search: The studied dyes have several conformers that could coexist in the solvent phase. A complete study considering the contribution of different conformers of the dyes would be closer to reality.Configurational search of the complex: The complex formed by the interaction of a dye with a graphene oxide model has several configurations with different relative energies. The global and local minima configurations should be considered for accuracy, weighted by their Boltzmann probabilities. It is important to state that this will be an expensive investigation necessary for accuracy.Environmental effects: In the current study, only implicit solvation has been considered to consider the environmental effects. A more accurate study including a few explicit water molecules would be welcome in the literature. Similar to the previous perspective, the current suggestion is foreseen to be an expensive procedure necessary for accuracy. Boltzmann weights should be used to consider the contribution of all possible configurations.This work lays a route for further theoretical investigations of graphene oxide as an adsorbent for emerging pollutants. As an introduction, this work has provided sufficient data to support the conclusion that graphene oxide can be a promising adsorbent for cationic dyes. Nevertheless, this work has limitations that need improvements in future studies. These limitations include the following:Supplementary file 1 (pdf 2976 KB)Supplementary file 2 (pdf 146 KB)Below is the link to the electronic supplementary material.


Sarcoidosis is a systemic, granulomatous disease of unknown etiology, most often manifested by mediastinal and hilar lymph node enlargement and parenchymal nodules in the lungs. However, it may involve any other organ. Neuro-sarcoidosis, a condition that affects up to 20% of sarcoidosis patients, can be found in any part of the central or peripheral nervous system and has important ophthalmic and neuro-ophthalmic manifestations. We present two patients with sudden vision loss due to neurosarcoidosis. In both cases, biopsy of the mediastinal lymph node showed non-caseating granulomas consistent with sarcoidosis. Treatment involved high doses of methylprednisolone intravenously, followed by topical dexamethasone eye drops in the first case and a systemic steroid treatment in the second, resulting in symptom relief. Those two cases demonstrate that sarcoidosis should be considered as a differential diagnosis in cases of optic neuritis. Sarcoidosis is a systemic, granulomatous disease of unknown etiology, most often manifested by mediastinal and hilar lymph node enlargement and parenchymal nodules in the lungs. However, it may affect any other organ . NeurosaThe most challenging manifestation of neurosarcoidosis is sudden vision loss, especially if it is the first manifestation of sarcoidosis. We describe two patients with this uncommon complication.A 44-year-old patient, non-smoker, presented himself at the emergency department elsewhere due to sudden onset of a vision loss in the right eye. He had a history of arterial hypertension, hyperlipidaemia and depression. The ophthalmological examination revealed oedema of the right optic nerve with narrowed peripheral vision. No signs of uveitis were found. The optical coherence tomography (OCT) demonstrated right papilledema . The cliA 63-year-old man with a history of benign prostatic hyperplasia, an ex-smoker with a history of 15 pack-years, presented himself to the general practitioner due to sudden onset of severe chest pain, that radiated to his back, the interscapular region, and the lumbosacral area, as well as circumferential pain around the subcostal region. The pain did not respond to any painkillers. The patient reported weight loss of 12 kg in the past 6 months due to reduced appetite, but denied cough, dyspnoea, haemoptysis and fever. Physical examination did not reveal any significant abnormalities. Laboratory tests showed a slightly elevated erythrocyte sedimentation rate (ESR) of 40 mm/h  and a CRP level of 36 mg/L , but were otherwise within normal limits. ANA and RF were negative. A chest CT revealed multiple enlarged mediastinal and hilar lymph nodes (up to 44 × 21 mm in diameter), as well as a 10 mm nodule in segment 6 of the left lung. Abdominal and pelvic CT showed several hypodense, small (4–6 mm) focal lesions in the liver, which were nonspecific, and a few nonspecific hypodense areas of bone rarefaction up to 6 mm in size in the lumbar vertebrae. Histological examination of the mediastinal lymph node (group 7) obtained by EBUS-TBNA showed non-necrotizing granulomas and confirmed the diagnosis of sarcoidosis. To assess the disease extent, a positron emission tomography (PET)-CT scan was performed, which revealed numerous metabolically-active lymph nodes symmetrically distributed in the mediastinum and hilar regions, as well as a few metabolically active and inactive nodules in the lungs, which were most likely granulomatous in nature, but no metabolically active lesions were found in the abdominal organs or bones. An MRI of the thoracic and lumbar spine showed four nonspecific intramedullary foci in the L2 and L4 vertebral bodies, and the Th9 and Th11 thoracic vertebrae, which enhanced peripherally with contrast, and could represent either atypical hemangiomas or sarcoid granulomas, but their nature could not be definitively determined at that time . The patThree years after the termination of the steroid treatment, the patient began to complain of progressive weakness. A CT of the chest confirmed the disease progression in the lungs. Normocytic anemia, hypercalcemia and a decrease in the estimated glomerular filtration rate (eGFR) were found in laboratory tests. The parameters of the pulmonary function tests were normal as previously. Echocardiography did not reveal any features suggestive of cardiac sarcoidosis or significant pulmonary hypertension. The loss of visual field in the right eye remained stable—the patient remained under the care of the ophthalmologist. Based on the overall clinical-radiological picture and additional diagnostic tests, a relapse of sarcoidosis with hypercalcemia and renal impairment was diagnosed. Prednisone was re-initiated with a dose of 40 mg/day. After one week of treatment, serum calcium levels normalized. The prednisone dose was gradually reduced to 10 mg/day. Partial regression of diffuse and nodular changes was observed in radiological imaging, with a significant increase in eGFR and resolution of anemia in laboratory tests. Since the onset of illness, the patient denied respiratory symptoms, and pulmonary function tests did not show any ventilatory abnormalities.The two abovementioned case reports describe patients with sarcoidosis complicated by optic neuritis. Neuro-sarcoidosis, a condition that affects up to 20% of sarcoidosis patients, can be found in any part of the central or peripheral nervous system and has important ophthalmic and neuro-ophthalmic manifestations ,10,11. MThe use of OCT has significantly improved the detection and treatment of retinal and choroidal disease. In sarcoidosis cases, OCT can provide clinicians with an improved ability to differentiate between subretinal and choroidal lesions, leading to more accurate differential diagnoses. Enhanced depth imaging (EDI), a special feature in modern OCT, allows for Bruch’s membrane penetration and enhances the resolution of the choroid . In the It is essential to distinguish between neurosarcoidosis and demyelinating optic neuritis, which is linked to multiple sclerosis (MS), especially in younger patients. Bilateral vision loss or features suggestive of chiasmal involvement may indicate demyelinating optic neuritis, rather than sarcoid-related optic neuropathy, which rarely presents as bilateral or chiasmal disease ,14. ChorThe diagnosis of sarcoidosis at this date is not standardized. According to the American Thoracic Society (ATS), the diagnostic pathway relies on three main criteria: a suitable clinical manifestation, the presence of non-necrotizing granulomatous inflammation in one or several samples of tissue , and ruling out other potential causes of granulomatous disease . The prep < 0.00001) [Large-scale randomized controlled trials (RCTs) have not been conducted to thoroughly investigate the effectiveness of any of the medications currently applied for the treatment of sarcoidosis ,2,17. By0.00001) . In bothIn sarcoidosis, numerous randomized controlled trials (RCTs) are currently in progress to assess the efficacy of new therapeutic compounds, innovative treatment targets, and alternatives to steroid treatment. Several of these trials have produced promising results in the initial phases .Sarcoidosis-related neuro-ophthalmic manifestations can include the orbital region, afferent and efferent pathways, and all components of the visual system. Isolated optic nerve involvement is insufficient to diagnose sarcoidosis, and other differential diagnoses such as meningioma or glioma should be excluded. In cases of optic neuritis, ophthalmologists should consult with other specialists and consider sarcoidosis as a potential diagnosis, if there is mediastinal and bilateral hilar lymphadenopathy . Ophthal


Research shows the benefits of music therapy for various mental health conditions, including depression, trauma, and schizophrenia. Music acts as a medium for processing emotions, trauma, and grief.Playing instruments can encourage emotional expression, socialization and exploration of various therapeutic themes .Group music therapy, measured by questionnaires and described in qualitative interviews, improved quality of life and self-esteem for people with severe mental illness (SMI).Group singing and song writing provide creative options for social connections. Music therapy should be considered as a component of holistic care for people with SMI. Jungup Lee, Thyer BA. May 2013Journal of Human Behaviour in the Social Environment 23(5):597-609Music therapy sessions are held in our hospital for people admitted to short-term hospitalization units and to psychosocial rehabilitation units. The goal of the sessions is to create a connection space, promote people’s confidence in their own resources for their recovery, and evoke valuable experiences and memories. Sometimes musicians from the community have been present in the sessions, contributing to overcoming the stigma towards mental illness.We describe self-assessment of people admitted to psychiatric units after attending music therapy sessions. People from brief hospitalization unit filled out a survey, after each session, voluntarily, about their emotional state at the beginning of the session and after it. People from rehabilitation units, voluntarily filled the SRS V.3.0. 2002-Miller. Duncan & Johnson escale.The SRS was designed for use by clinicians to assess the therapeutic alliance during therapy  3-12 12/14/04 3:53 PM Page 3).23 sessions took place for each unit. 39 patients from brief hospitalization, 22 women and 17 men, attended the sessions. 15 had a diagnosis of schizophrenia and related disorders, 13 were affective disorders, and 11 others diagnosis. All of them liked the participation either fully or partially. 76% men and 77% women felt better after, none of them reported to feel worse. 82% men and 86% women replied they would repeat the session.I felt heard, understood, and respected/ We worked on and talked about what I wanted to work on and talk about/ The therapist’s approach is a good fit for me) with an overall score of 9,62 over 10 .Patients from rehabilitation units were 7 women and 10 men. 14 had a schizophrenia related disorder and 3 had bipolar disorder. All items on the scale were scored above 9 over 10, (Music therapy sessions achieve benefits on an emotional level in any of the diagnoses, improving alliance with care teams, who value sessions as normalizing spaces, helping to overcome stigma.None Declared


As a unique ecosystem, Karst caves harbor an impressive diversity of specific fungi. However, the factors and mechanisms that shape fungal biodiversity in caves remain elusive. In this study, we explored the assembly patterns of fungal communities based on our previous research in eight representative Karst caves in Southwest China. Our results indicated that dispersal limitation plays a crucial role in shaping the overall fungal community as well as specific communities in rock, sediment, and water samples. However, “Undominated” processes contributed more than dispersal limitation in air samples. Interestingly, the dominant assembly processes varied between caves. Consistently, environmental selection had a minor impact on the assembly of fungal communities. Among the examined spatial and environmental variables, latitude, longitude, altitude, and temperature were found to significantly influence fungal communities irrespective of substrate type. These findings provide valuable insights into the ecological factors governing fungal community assembly in Karst caves. Understanding the assembly processes and mechanisms that shape community diversity, biogeography, succession, and function is a prominent topic of study in ecology, particularly in microbial ecology. However, most of these processes are still not well-understood or are highly controversial ,2,3,4. DCaves are unique ecosystems with distinct characters that differentiate them from outside environments, making them ideal conditions in which to test community assembly theories ,7. HowevBy collecting a large number of air, rock, sediment, and water samples from eight representative Karst caves in Southwest China, Zhang et al. systematically investigated the diversity, composition, and controlling factors of fungal communities in Karst caves using a high throughput sequencing method . In the Samples and molecular data used in this analysis were acquired from our previous study . In brieTotal genomic DNA was extracted using a FastDNA Spin Kit  according to the manufacturer’s instructions. The ITS1 rDNA region of each sample was amplified using the primer pair ITS1F/ITS2  with equRaw sequences were paired using FLASH (v1.2.11) , and theBray) were calculated using Rscript “bNTI_Local_Machine.r” written by Stegen et al. [Bray value was used to further resolve the pairwise comparisons that were assigned to stochastic processes [Bray < –0.95 and RCBray > 0.95 indicate a relative dominant influence of homogenizing dispersal and dispersal limitation, respectively, and RCBray values < 0.95 represent a crucial role for “Undominated” assembly, including weak selection, weak dispersal, diversification, and/or drift [p-value were calculated to explore the associations between βNTI values and changes in environmental variables in different samples. Meanwhile, Pearson’s correlation coefficients between fungal community Bray–Curtis similarities and geographic distance between samples were calculated to determine the spatial predictors of fungal community composition. The geographic distance (in km) between each sample, i.e., the straight-line distance between the sampling points, was calculated using the R package geosphere (v1.5) [To quantify the relative importance of stochastic and deterministic processes that drive fungal community assembly, beta nearest-taxon index (βNTI) and Bray–Curtis-based Raup–Crick   based on4+, N/NO3−, TP, and TS) variables together [A variation partition analysis (VPA) using distance-based redundancy analysis (db-RDA) was performed to determine the relative proportions of community variations that can be explained by spatial  and environmental  were clustered at a 97% similarity from 6,618,705 clean reads. Among the non-rare OTUs, 10,769 OTUs, accounting for 97.4% of the clustered reads, were assigned into the fungal kingdom . Before Bray indices were calculated to explore the relative importance of stochastic and deterministic processes in the assembly of the fungal community in caves  and water  communities, while temperature and altitude played more important roles in the rock  and sediment  communities (In the case of air samples, the fungal communities were significantly influenced by latitude, longitude, altitude, and temperature, while air humidity and sample distance from the entrance did not show significant effects a. Similamunities .Various fundamental biodiversity patterns have been observed in ecology ,37. HoweIn the current study, it was found that stochastic factors were the dominant drivers of fungal community assembly in Karst caves on a large scale. Stochastic processes have been recognized as controlling processes of microbial biodiversity in various studies ,38,39,40It is noteworthy that the importance of “Undominated” processes in the community assembly of air samples is greater than that of dispersal limitation c. There The dominant processes controlling community assembly in single caves were observed to be in contrast to our hypothesis. Dispersal limitation was found to be predominant in six caves, while homogeneous selection and “Undominated” processes were dominant in the remaining two caves. This contrast may be attributed to the specific structure and conditions present in each cave. For example, some caves are strongly zonal, while others consist of several large halls. Additionally, the influences of external communities, as well as animal and human activities, on fungal communities differ among caves. For instance, Zhang et al. found that fungal communities in Karst caves were greatly influenced by fungal communities in external environments due to airflow exchange ,45. MeanConsistent with the findings of Zhang et al. , our stuIn conclusion, our study provides a preliminary quantification of the assembly patterns of fungal communities in Karst caves, based on our previous investigation of fungal communities in eight caves in Southwest China. We found that dispersal limitation plays a crucial role in shaping both the overall fungal community and specific communities in rock, sediment, and water samples. However, “Undominated” processes have greater influence on the air fungal community compared to dispersal limitation. Moreover, the dominant processes differ between each cave. VPA analysis revealed that the environmental selection plays a minor role in the fungal community in caves. Among the spatial and environmental variables examined, latitude, longitude, altitude, and temperature significantly affect the fungal communities across all substrates. Overall, our study provides a valuable insight into the mechanisms and factors that control the assembly of fungal communities in Karst caves, which may contribute to further exploration and conservation efforts for microbial communities in these unique environments.


Using the fantastic features of the graphene/CaF2 multilayer, this article proposes an improvement sensor in the sensitivity (S), the figure of merit (FOM), and the quality factor (Q). The proposed sensor is based on the five-layers graphene/dielectric grating integrated with a Fabry–Perot cavity. By tuning graphene chemical potential (µc), due to the semi-metal features of graphene, the surface plasmon resonance (SPR) waves excited at the graphene/dielectric boundaries. Due to the vertical polarization of the source to the gratings and the symmetry of the electric field, both corners of the grating act as electric dipoles, and this causes the propagation of plasmonic waves on the graphene surface to propagate towards each other. Finally, it causes Fabry–Perot (FP) interference on the surface of graphene in the proposed structure's active medium (the area where the sample is located). In this article, using the inherent nature of FP interference and its S to the environment's refractive index (RI), by changing a minimal amount in the RI of the sample, the resonance wavelength (interferometer order) shifts sharply. The proposed design can detect and sense some cancers, such as Adrenal Gland Cancer, Blood Cancer, Breast Cancer I, Breast Cancer II, Cervical Cancer, and skin cancer precisely. By optimizing the structure, we can achieve an S as high as 9000 nm/RIU and a FOM of about 52.14 for the first resonance order (M1). Likewise, the remarkable S of 38,000 nm/RIU and the FOM of 81 have been obtained for the second mode (M2). In addition, the proposed label-free SPR sensor can detect changes in the concentration of various materials, including gases and biomolecules, hemoglobin, breast cancer, diabetes, leukemia, and most alloys, with an accuracy of 0.001. The proposed sensor can sense urine concentration with a maximum S of 8500 nm/RIU and cancers with high S in the 6000 nm/RIU range to 7000 nm/RIU. Also, four viruses, such as M13 bacteriophage, HIV type one, Herpes simplex type 1, and influenza, have been investigated, showing Maximum S (for second resonance mode of λR(M2) of 8000 nm/RIU (λR(M2) = 11.2 µm), 12,000 nm/RIU (λR(M2) = 10.73 µm), 38,000 nm/RIU (λR(M2) = 11.78 µm), and 12,000 nm/RIU (λR(M2) = 10.6 µm), respectively, and the obtained S for first resonance mode (λR(M1)) for mentioned viruses are 4740 nm/RIU (λR(M1) = 8.7 µm), 8010 nm/RIU (λR(M1) = 8.44 µm), 8100 nm/RIU (λR(M1) = 10.15 µm), and 9000 (λR(M1) = 8.36 µm), respectively.One of the primary goals for the researchers is to create a high-quality sensor with a simple structure because of the urgent requirement to identify biomolecules at low concentrations to diagnose diseases and detect hazardous chemicals for health early on. Recently graphene has attracted much interest in the field of improved biosensors. Meanwhile, graphene with new materials such as CaF Because of this quick real-time detection, optical biosensors are also often used in medical applications2, environmental applications3, industrial applications4, etc. There are two primary approaches for using optical biosensors to find or sense biomolecules. Fluorescence is the foundation of the first detection approach, while label-free detection is the second. Of these two techniques, fluorescence-based detection employs biomolecular tags to find them. Although the Fluorescence approach is accurate, labeling all the samples makes it hard to use. On the other hand, this approach is expensive. Therefore, the second method has been widely used5.Recently, Optical biosensors have been the most efficient since they can detect biomolecules directly and instantly8. In contrast with the first approach, label-free techniques measure an inherent property of the query itself , thereby avoiding modifying interactors9. The successes of sensing technologies are determined mainly by their S, resolution, and detection limit. Dynamic range, real-time monitoring, multiplexing and HT capability, widespread applicability, and data handling are other key determining factors11.The label-free detection of biomolecules can be realized by the excitation of SPR in waveguides, photonic crystal fibers, and Bragg gratings12.In protein microarray experiments, signals can be detected by label-based or label-free strategies. Both approaches have their merits and demerits. Label-based detection methods require labeling query molecules with fluorescent dyes, radioisotopes, or epitope tags. Label-based detection is widely used in protein microarrays due to the expected availability of reagents and simple instrument requirements. However, these labeling strategies often alter the query molecule's surface characteristics and biological activities. Moreover, the labeling procedure is laborious and lengthy, limiting the number and types of query molecules that can be studied13. SPR technology detection in biosensors can also limit drug-serum interactions14. Using localized surface plasmon-based biosensors, which can detect biomolecules, facilitates the diagnosis of Alzheimer's disease15.Meanwhile, in many cancer situations, SPR sensors are helpful for drug discovery19, photodetectors21, sensors23, and Optical Tweezers26, graphene has been in the center of researchers' attention. This single-layer graphite allotrope known as graphene has unique optical and electrical features such as high carrier mobility, electrostatic doping, ultra-wide absorption spectrum27, easy fabrication while being compatible with well-established silicon technology28, and ultrafast charge carrier dynamics, which is originated from its 2D nature29. Nowadays, due to graphene's extraordinary optical and electrical characteristics, graphene-based SPR sensors are generating interest. It has been reported that graphene-based SPR sensors are suitable for biological applications with great features. Additionally, a graphene layer on the sensing medium results in superior conductivity and stable biomolecule absorption. The large carbon-based rings in biomolecules are the primary cause of a biomolecule's absorption by a graphene sheet30.In recent years, with the emergence of graphene and its applications in the electronics and photonics industry, such as optical modulatorsGraphene-based SPR sensors employ the shift in the graphene plasmon resonance wavelength to identify slight variations in the RI of the medium close to the graphene-based structure. Graphene-based sensors have made considerable advances in terms of sensing speed and structuring. Likewise, it can absorb bio and polar molecules well due to its high surface-to-volume ratio. Therefore, using graphene, electromagnetic waves could be coupled to the bound collective charge oscillations, forming localized SPR (LSPR).2 and graphene, has been reported31. The simulation results demonstrate multi-resonant modes suitable for ultrasensitive refractive index sensing. Also, a graphene-gold grating in the near-IR region has been proposed32, which performs well for detecting biomolecules and harmful gases for health. Absorption spectra of this structure indicate two resonance modes with S as high as 1100 nm/RIU and 1180 nm/RIU.Recently, prominent studies involving graphene grating structures have been reported. For instance, a graphene plasmonic grating ultrasensitive tunable terahertz sensor, which consists of SiO2 multilayer for detecting and sensing changes in the RI of samples (and thus the concentration) of gases, biomolecules, urine, and generally all materials with a refractive index between 1.000 and 1.800. Also, some cancers such as Adrenal Gland Cancer, Blood Cancer, Breast Cancer I, Breast Cancer II, Cervical Cancer, and skin cancer have been investigated precisely. This structure consists of five graphene layers separated by CaF2 layers and covers the grating structure's steps that form strong SPs in the mid-IR region. CaF2 has been used as a substrate material for graphene not only to increase the graphene plasmonic waves quality (due to zero imaginary part of permittivity in the wavelength range of interest) but also due to the high dielectric constant and its breakdown voltage, it causes to shift graphene chemical potential with very low gate voltage. Moreover, due to an ingenious method in which a polarized light source causes both edges of gratings to act as an electrical dipole, the excited plasmonic waves propagate toward each other and form an FP interference. This FP interferometer makes the primary mechanism of the proposed biosensor. Since FP interference is highly sensitive to its medium RI, the proposed design shows significant improvement in S, FOM, and Q. Additionally, research has been done on the potential sensing properties of various gas alloys and biomolecules. The proposed sensor can sense urine concentration with a maximum S of 8500 nm/RIU and cancers with high S in the 6000 nm/RIU range to 7000 nm/RIU. Also, four viruses, such as M13 bacteriophage, HIV type one, Herpes simplex type 1, and influenza, have been investigated, showing a Maximum S of 8000, 12,000, 38,000, and 12,000 nm/RIU, respectively.This paper proposes a structure and a novel method based on propagating plasmonic waves interferometer on graphene/CaF2 layers and cover the surface of gratings, which results in high electric field confinement. In addition, these gratings are created from CaF2, which is on the top of the gold substrate and serves as the gate voltage for adjusting the Fermi level of the graphene. In addition, to obtain realistic results, we rounded the grating corners in all simulations.A 3D view of the proposed sensor and its cross-section is shown in Fig. 26.This paper uses graphene as a 2D sheet with its surface conductivity. The surface conductivity of graphene can be separated into interband conductivity, which is the first term of Eq. , and intf is the Fermi energy, B is the Boltzmann constant, T = 300 K is the temperature, e is the elementary charge, ω is the angular frequency, and τ is the relaxation time, respectively. Here the intrinsic relaxation time is taken to be In Eq. , Ef is t2 layer and is taken 1 m2/Vs.,34. Figure The scattering rate is obtained by entclass1pt{minimaThe parameters shown in Fig. Most previous spp-based sensors consist of a prism substrate, a dielectric layer, novel metal film, liquid, and plasmon, which can only be excited by TM polarization (Kretschmann configuration) and have a large footprint after that, grating-based graphene sensors reached interests of researchers. Grating couplers have not been used in SPR sensors as widely as prism couplers. However, their compatibility with mass production and the prism's absence make grating-coupled SPR attractive for fabricating low-cost, compact-sensing devices.max is the change in the maximum wavelength of the absorption curve for a slight shift (Δn) in the RI of the material we want to measure, the figure of the merit (FOM) for the proposed sensor is calculated as Eq.  area is the optimum spectral range for biomolecule sensing since it doesn't result in photodamage. An optical sensor's detection accuracy will gradually increase if operated in the spectrum's infrared (IR) region since bio samples absorb considerably more in this region than in the visible area, which may also be connected to penetration depth towards the sample side.2), fluoride glass can meet the qualities mentioned earlier among other substrate glass materials for applications in the IR region. CaF2 with a low RI value can also provide superior error rejection (mainly angular) during mechanical setup. Consequently, CaF2 might be a suitable substrate for SPR-based IR applications35. Therefore, recently it has been shown that CaF2-based SPR sensor provides much better S than conventional dielectrics such as SiO2.A suitable substrate material should have good transparency, low refractive index (RI) discrepancy by varying the temperature, a big transmission window, and a high laser damage threshold in the Mid-IR spectral range. Like calcium fluoride 36:r is the dielectric function, and λ is the wavelength in μm.The approached experimental data of the permittivity of CaF2 a proper dielectric and spacer material for graphene in the wavelength of interest. Also, the mentioned features of CaF2 make it a very suitable substrate for graphene, preventing secondary effects and increasing graphene improvement.As shown in Fig. The optical analysis uses the FDTD method, and a normal incident with a linearly polarized source is employed to illuminate the structure. Its E-field is polarized perpendicularly to the gratings (in the x-direction). It is worth mentioning that the incident light that polarized parallel to the grating’s direction (in the y-direction) cannot activate the plasmon resonance because the structure entirely reflects it. The boundary conditions in the z-directions are Perfectly Matched Layers (PMLs), while the x and y directions are periodic.x37, SOx, and Cox38. In addition, since the number of blood illnesses and other forms of cancer continues to rise, there is a pressing need to detect origins and target tissues. For instance, some research has been conducted on the hemoglobin value of blood39 and the ability to see certain types of cancer, such as liver, blood, and breast, using an optical method. In this paper, we calculate the influence of the RI change of an analyte when it changes between 1 and 1.6, while the RI of the medium is assumed to be n = 1.33.One way to determine an analyte's concentration or perform a biophysical analysis is to evaluate the variation in the RI. Many biomolecules have refractive indices between 1.300 and 1.600, while the refractive index of most gases ranges from 1.000 to 1.600, such as NOFirst, we examine the effect of graphene layer number on proposed biosensor S. Figure In addition, the S of each case is written in the inset of Fig. As shown in Fig. 2 sandwich structure. As shown in Fig. Figure 2 layers. Therefore, we continue our simulation and calculations for a proposed biosensor with five graphene layers after this.Comparing Figs. We simulated wavelength-dependent absorption for various graphene Fermi levels, as shown in Fig. 2 is the most crucial gas (n = 1.0002) detected using the proposed sensor. Moreover, some biomolecules, such as MCF-7 (n = 1.401) and MDA-MB-231 (n = 1.399), can be used to diagnose breast cancer, and Jurkat biomolecule (n = 1.390), which is used to detect leukemia, respectively, are in this system identification region40 and can be easily detected by the proposed sensor.Figure As evident from Fig. Figure Finally, Fig. 41. These results have been compared to other SPR-based sense methods, such as fiber optics, which can sense RI with an accuracy of Δn = 0.01 42, gold grating on SiO2, which is capable of detecting samples with an accuracy of Δn = 0.005 per RI unit43. In contrast, the proposed structure can sense refractive indices with a precision of less than 0.001.Additionally, the RI discrepancies between liver cancer cells (HCC = 1.347) and normal liver cells (NHCC = 1.345) are from the rank of 0.002, which can be identified using the suggested biosensor44. The refractive index of a patient with diabetes mellitus is relatively high. The mean refractive index of morning urine samples ranges from 1.336 ± 0.0019. In contrast, the refractive index of specific random samples is 1.335 ± 0.0017. As clear from Fig. Different glucose concentrations found in urine samples range in refractive index from 1.332 to 1.340Figure By looking precisely at Fig. Table Diabetes mellitus is a chronic metabolic condition that affects millions of people worldwide. This article examines the response of a graphene grating-based sensor to the refractive index of urine samples  to diagnose diabetes mellitus. Evanescent field interaction with the high glucose concentration, known as "hyperglycemia" (RI 1.347) sample over the proposed sensor, causes the refractive index to change. The proposed biosensor can also help detect low glucose levels (RI 1.2) and is named "hypoglycemia."Physically, a urine sample will change the surface tension, gravity, and refractive index due to the presence of glucose. Specific characteristics of label-free biosensing are their resistance to electromagnetic interference, compact design, the potential to integrate into the lab on a chip, etc. these sensors lead to significant developments in diagnosis, food safety management, pharmaceutical development, and monitoring of environmental hazards, and recently, it has become crucial to use a noninvasive glucose sensing method compared to the traditional blood pinpricking method. Also, some cancer such as Adrenal Gland Cancer, Blood Cancer, Breast Cancer I, Breast Cancer II, Cervical Cancer, and skin cancer have been investigated precisely.Figure µm to almost 6400 nm/RIU where the incident wavelength has been fixed to 14.05 µm. Also, the structure can sense Skin Cancer with a maximum S of nearly 6350 nm/RIU at 13.9 µm.Although the S fluctuation of the proposed structure concerning wavelength variations is insignificant for the diverse types of cancers shown in Table As evident from Fig. 51. Moreover, (MDA)-(MB)-231 and MCF-7 are classified as Types I and II of breast cancer, respectively. The S of each cancer can be defined as the shift in the absorption of the proposed structure when the refractive index changes from cancer RI to its normal cell RI. For example, the Jurkat cell or blood cancer has a refractive index of 1.39 with an 80% concentration, while its normal cell refractive index is 1.37653. Also, the refractive index of Cervical cancer with an 80% concentration is 1.392, as shown in Table 58. The refractive index of Adrenal Gland Cancer is 1.395 with an 80% concentration, and its normal cell owns a RI of 1.381 in the 30–70% concentration59. Also, Breast cancer I and type II own the normal cells with the RI of 1.385 and 1.38760. Finally, the RI of skin cancer  with an 80% concentration is 1.38, and its normal cell  RI with a concentration in the range of (30% to 70%) is 1.3661.The lists of refractive indices for the various cancer cells employed in this study are shown in Table 62. For example, the RI of the human immunodeficiency virus (HIV) is 1.5, which is entirely covered by the proposed structure. Table 63 inside a fluidic medium with its radius obtained from62.The capability of our proposed structure is not limited to these; the proposed sensor can identify and sense viruses inside the sample. The RI of different viruses is given in the previous literatureThe S of the proposed multilayer graphene sensor is compared in Table 2 gratings. The sensing medium is set between two grating structures. Modifying the structure made it possible to get the highest S, 8500 nm/RIU, and the FOM 52.14 for the first mode (mode 1) and the outstanding S, 10,000 nm/RIU, and the FOM 81 for the second mode (mode 2) for diabetes sensing. Our proposed method and structure can open a new door for integrated optical applications. Since most plasmonic-based sensors structure has a metallic shape to induce LPR in a metal–dielectric interface, our proposed sensor, by taking advantage of the semi-metal feature of graphene, can efficiently generate the plasmonic waves on the graphene surface, which finally, due to propagating the plasmonic waves on graphene surface in the opposite direction, the FP interference has happened which is the base mechanism of the sensing in the suggested biosensors. Also, it is evident that using metal on a graphene surface makes the fabrication process difficult and causes second-order effects. Since FP interference is highly sensitive to its medium RI, the proposed design shows significant improvement in S, FOM, and Q. Additionally, research has been done on the potential sensing properties of various gas alloys and biomolecules. The proposed sensor can sense urine concentration with a maximum S of 8500 nm/RIU and cancers with high S in the 6000 nm/RIU range to 7000 nm/RIU. Also, four viruses, such as M13 bacteriophage, HIV type one, Herpes simplex type 1, and influenza, have been investigated, showing Maximum S of 8000, 12,000, 38,000, and 12,000 nm/RIU, respectively.This study developed a high-performing RI sensor for sensing gas alloys, biomolecules, cancers, and viruses using the excitation of propagation SPs waves in multilayer graphene gratings. For better binding between gas alloys or biomolecules and cancers with a label-free SPR sensor to increase the performance of the proposed design, five graphene layers are embedded in the CaF


Rapid progress in nanotechnology has advanced fundamental neuroscience and innovative treatment using combined diagnostic and therapeutic applications. The atomic scale tunability of nanomaterials, which can interact with biological systems, has attracted interest in emerging multidisciplinary fields. Graphene, a two-dimensional nanocarbon, has gained increasing attention in neuroscience due to its unique honeycomb structure and functional properties. Hydrophobic planar sheets of graphene can be effectively loaded with aromatic molecules to produce a defect-free and stable dispersion. The optical and thermal properties of graphene make it suitable for biosensing and bioimaging applications. In addition, graphene and its derivatives functionalized with tailored bioactive molecules can cross the blood–brain barrier for drug delivery, substantially improving their biological property. Therefore, graphene-based materials have promising potential for possible application in neuroscience. Herein, we aimed to summarize the important properties of graphene materials required for their application in neuroscience, the interaction between graphene-based materials and various cells in the central and peripheral nervous systems, and their potential clinical applications in recording electrodes, drug delivery, treatment, and as nerve scaffolds for neurological diseases. Finally, we offer insights into the prospects and limitations to aid graphene development in neuroscience research and nanotherapeutics that can be used clinically. This enin vitro because of their physical and chemical properties  materials have been extensively explored for biomedical applications . With suPrevious studies have shown that graphene can aid in the adhesion and differentiation of neurons and can act as a neuroprotective agent. Graphene is a potential carrier to control drug release at specific disease sites, making it a valuable treatment strategy for neuronal diseases. Moreover, graphene and its derivatives can be used as scaffolds to enhance nerve repairing, establishing it as a next-generation candidate for advancing medical bioengineering. However, the safety of nanomaterials is essential to protect human health and ensure environmental safety. Thus, further studies are warranted to fill the knowledge gap on the limitations of carbon nanomaterials, including their toxicity and biocompatibility .In this review, we focus on novel graphene applications in the nervous system. Graphene-based materials may be used clinically in the future; however, this article is limited to pre-clinical applications. We aimed to describe the properties of graphene-based materials applicable in neuroscience research, including using them as electrodes for neural recording and imaging, neural cell substrates, photothermal effects, and drug and gene deliveries. Furthermore, we aimed to outline the application of graphene-based materials in neurological diseases and neural tissue engineering. Finally, we aimed to discuss graphene’s cytotoxicity and provide an overview of its prospects.2.−1, superior to graphene grown on indium tin oxides. Unfortunately, this technique requires a very high temperature and vacuum environment, as well as exorbitant prices for only small-size devices. Many graphene-based nanomaterials are built up mostly by chemical reactions for covalent bonding, such as graphene oxide [GO; Graphene is a sheet comprising a single layer of carbon atoms formed by stripping highly oriented pyrolytic graphite, like carbon nanofibers, another type of nanomaterial. In 2D, sp2 hybridized carbon atoms give graphene a hexagonal honeycomb lattice pattern with a thickness of approximately 0.335 nm [At room temperature, the interactions between carbon atoms in graphene are strong. Electrons in the carbon atoms are not easily affected or scattered by the movement of surrounding carbon atoms; its conductivity also contributes to electron transfer . Additio3.Neural interfaces are typically implanted with electrodes that can record or stimulate target tissues or cells in the brain, thereby establishing connections with the nervous system . Howeverin vivo microscopy techniques performed on freely behaving animals. However, one of the major problems of using graphene in in vivo studies is that it is ultra-flexible and difficult to implant surgically. Graphene can be mechanically deformed beyond the linear regime ; this isin vivo neural recording by graphene electrodes compared to gold electrodes  for recording cellular activity is challenging. Studies have demonstrated effective ectrodes . In thesectrodes . Recentlin vivo recording validation.The mechanical properties, electrical conductivity, and large surface area of graphene make it perfect material for developing ideal neural interfaces and more reliable electrodes, while highlighting the unique advantages of composites, demonstrating greater application potential in neural interfaces. However, more studies are required to investigate the long-term effects of graphene-based nanoelectrodes during 4.Traditional metal electrodes used for recording electrophysiological activities obstruct the vision field, produce optical shadows, and are more likely to introduce light-induced artifacts during the recording. Researchers have discovered that transparent graphene could solve this problem due to the unique band structure in the transmission spectrum of graphene that prevents the mentioned limitations. Theoretically, graphene allows the hot ballistic charge carriers produced by light  to transin vivo. in vivo. Moreover, these cellular-scale methods enable the recording of electrophysiology and calcium fluorescence in CA1 pyramidal neurons in hippocampus seizures  region . Recentlin vivo and achieved ultra-efficient tumor ablation after laser treatment. Similarly, in vitro. However, the rGO-PEG showed concentration-dependent cyto- and geno-toxicity. No toxic signal was found in the histological examination of GO-PEG during PTT by Liu operation. Another transition metal disulfide that is attracting more interest in the biomedical field is Tungsten disulfide because of its photothermal properties, high lubricity, and catalytic activity. Its high NIR absorption capacity has been applied to photothermal therapy of tumors .PTT has received widespread attention because it can thermally ablate cancer cells in a minimally invasive manner under an NIR laser. The broad optical absorption spectra are important in photothermal medical applications. Nanomaterials with strong absorption in the NIR regime can act as effective PTT absorbers that achieve therapeutic temperatures with less total light energy, reducing heat escaping from the target to healthy surrounding tissue and avoiding tissue damage. GO and rGO have been widely exploited as effective absorbers for NIR-based PTT in cancer therapy . Clinicaf tumors . The devPhotoacoustic and fluorescence imaging can also be combined with PTT for diagnosis. Photoacoustic imaging has few specific signals and cannot image deep tissues. Fluorescence imaging does not use ionizing radiation and has low tissue penetration. Thus, further research is needed to fully understand how to apply carbon nanomaterials better and fully in neurology, as their functions involve the interaction between their various properties. Therefore, improving the functionalization of nanomaterials, which can create better and less risky options for patients during clinical treatment of diseases, remains challenging.5.9 W m−2 K−1. −1 K−1.Graphene has high thermal conductivity (κ) and great thermal management potential, indicating its development in nanoscale engineering for heat transport and management. Researchers have suggested various effective approaches for modulating the thermal conductivity of graphene. Depositing nanoparticles on the surface of graphene can mediate its thermal management . Chemicain vivo  accumulation. Recently, As thermal stability improves, graphene use has risen in the fields of clinical biomedical application and tailored nanomedicine for neurologic diseases. For example, graphite lattices in the graphene family of nanomaterials fuse to form disparate forms of molecules, with a potential role in drug and gene delivery for treating neurological diseases. Using two complementary strategies for conferring static or spatial stability can improve the thermal stability of graphene and allow cells to occupy stable graphene sheets . In 2008in vivo . The comThese findings provided new ideas for combining PTT and graphene-based drug/gene delivery therapy and demonstrated a significant improvement over traditional surgical treatment method. Graphene-based materials showed high potential for the novel and efficient treatment of neurological disorders. However, the interaction between graphene and cells may interfere with the different cell viability reduction rates in thermal therapy . Future 6.The first aspect to consider when developing graphene-based biomedical applications is their biocompatibility to avoid any adverse effects on living tissues . GraphenGraphene biocompatibility and its effects on the performance of living cells have shown that graphene on top of matrix substrates does not impede the interaction between neurons and substrates, thus maintaining neuronal viability . Li et ain vivo studies have demonstrated that the immune system is highly sensitive to graphene and quickly responds by increasing anti-inflammatory cytokine synthesis (in vivo zebrafish model (in vivo settings. Fabricating graphene with poly(ε-caprolactone) caused an acceptable degree of immunological response in vivo  in in vivo mouse experiments did not accumulate in main organs with fast kidney clearance, probably due to their ultra-small size  and low (up to 70 kΩ−1) conductivity favored neuron spreading without clear alteration, indicating that the high electrical conductivity of graphene is not the crucial property and the efficient range of its electric conductivity for graphene-based neuronal interfaces is broader than expected  to ensure the delivery of sufficient dosage to kill cancer cells. Second, the delivery should specifically target cancer cells, avoiding harmful effects on normal tissues. For example, subarachnoid hemorrhage occurs in severe neurological diseases, and studies have demonstrated the feasibility of using functionalized GO (FGO) for effective drug delivery in such cases. The content of FGO nanotablets loaded with pirfenidone, which is used to treat subarachnoid hemorrhage, gradually increases with an increase in drug concentration , making 1-42 (Aβ1-42) is an important biomarker in AD and PD  in neuroscience in e repair , we founin vitro and in vivo studies suggest that current studies have several limitations. First, compared with the number of in vitro studies, in vivo studies exploring the basic properties of graphene, specifically its biocompatibility and toxicity are limited. Lack of consistency between in vitro and in vivo results may downgrade graphene into only a research tool. Regarding in vivo study models, nearly all animal models are limited to mice, and no other species have been considered in exploring graphene applications. Second, most studies suggest that nanomaterials induce a mild immune response. However, researchers are yet to identify the standard method of administration. Furthermore, whether nanomaterials act the same way when eliciting an immune response via different routes of administration in vivo remains unknown, although the toxicity and pharmacokinetics of nanoparticles are closely dependent on the administration route. Third, most studies, whether in vitro or in vivo, did not perform in-depth investigations on the underlying mechanism involved in the relationship between cell differentiation and graphene-based substrates, such as induced morphologic interplay and cellular modulation pathways. Without these fundamental definitions, determining the role of graphene in biomedical applications may be challenging.The observed discrepancies in in vivo because the results from in vitro studies cannot be directly applied to humans. Moreover, the graphene-based implant as an electrode or scaffold should also be further investigated to observe its long-term effect in vivo. More animal models should be considered to clarify the relationship between different species and graphene. Second, graphene can exhibit long-term and short-term toxic effects on the same cell and can potentially cause long-term damage to cellular structures. This review highlighted that graphene toxicity is highly dependent on excretion, functionalization, size, and structural dimensions. Therefore, comparing graphene toxicity between different experiments is difficult, given its diversity in shape, surface, size, and fabrication. Thus, the fabrication and terminology of graphene and the examination of toxicological methodologies must be standardized. This will better aid the understanding of the physicochemical properties and potential toxicity of graphene in vivo and in intro, allowing its practical application in humans. Third, future studies should incorporate graphene with various optical components to probe deeper brain tissues and understand how brain circuits process information because a graphene electrode with a two-photon microscope can record the whole cortical surface in neuroscience investigation. Moreover, electrical stimulation has been clinically applied in rehabilitation after nerve injury. Graphene-based conduits have shown great potential in nerve repair as scaffolds. Future studies should measure the potential of combining electrical stimulation and graphene-based conductive scaffolds in clinical nerve repair.The following are proposals for future experiments for improving graphene and its derivatives development: First, the main consideration of nanomaterials in biomedical application is their biocompatibility. Further studies must focus more on biocompatibility and toxicity This review sheds light on the safety and biological properties of graphene that must be considered before the utilization of graphene-based therapy for human benefit. This may pave the way for using graphene and its derivatives as powerful materials with versatile scientific and clinical applications.TY and YY wrote the first draft of the manuscript. L-YM and YL wrote sections of the manuscript. JB, F-YW, and LZ reviewed the literature. All authors contributed to manuscript revisions as well as read and approved the submitted version.This work was supported by the National Natural Science Foundations of China , the Innovation Team Project of Yanbian University (China), and the International Cooperation Project of Science and Technology Department of Jilin Province (20210402004GH).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Tunable and low-power microcavities are essential for large-scale photonic integrated circuits. Thermal tuning, a convenient and stable tuning method, has been widely adopted in optical neural networks and quantum information processing. Recently, graphene thermal tuning has been demonstrated to be a power-efficient technique, as it does not require thick spacers to prevent light absorption. In this paper, a silicon-based on-chip Fano resonator with graphene nanoheaters is proposed and fabricated. This novel Fano structure is achieved by introducing a scattering block, and it can be easily fabricated in large quantities. Experimental results demonstrate that the resonator has the characteristics of a high quality factor  and low state-switching power (∼1 mW). The temporal responses of the microcavity exhibit qualified modulation speed with 9.8 μs rise time and 16.6 μs fall time. The thermal imaging and Raman spectroscopy of graphene at different biases were also measured to intuitively show that the tuning is derived from the joule heating effect of graphene. This work provides an alternative for future large-scale tunable and low-power-consumption optical networks, and has potential applications in optical filters and switches. In the past decade, silicon photonic integrated circuits (PICs) have been regarded as one of the most promising platforms for realizing high-performance and multifunctional on-chip photonic devices. Microring resonators (MRRs), as one of the most fundamental components in silicon PICs, are widely used in the area of modulation ,2, filteThermo-optic tuning is an effective way to realize tunability owing to the large thermo-optic coefficient of silicon   material composed of a single layer of carbon atoms, has been extensively investigated due to its diverse and charming optoelectronic properties ,18,19,202/V·s ,22. In t2/V·s ,24, prov2/V·s . On the 2/V·s ,28,29,30To further improve the performance of this type of devices, in this paper, we present a thermally tunable resonator that combines graphene nanoheaters with high heating efficiency and Fano resonators with low switching-energy requirements. The Fano resonator is achieved via the incorporation of microring resonators (MRRs) with a scattering rectangle block that could be easily fabricated using deep ultraviolet (DUV) lithography. Experimental results demonstrate that the Fano resonator with a graphene nanoheater requires only ∼1 mW for “on/off” state switching, and has a narrow line width of ∼0.05 nm, outperforming previous on-chip thermally tunable silicon devices . The resFano resonance is a widely known phenomenon that occurs when a narrow discrete constructive or destructive state interferes with the continuum band of states . CompareTo achieve asymmetric Fano line shapes, as shown in R = 30 μm, To plot the theoretical transmission spectra, we set the parameters as follows: cies see .Sample fabrication. The Si photonic platform was prepared by the MPW foundry  with standard processes of DUV lithography and inductively coupled plasma etching, followed by the deposition of 2 μm thick silica as the upper-cladding layer. To avoid the crack of graphene caused by the height difference of the waveguides, we then used a CMP machine (LOGI TRIBO) to planarize the top surface of the silica and thin it down to about 180 nm. The thickness of the top silica layer was measured with the ellipsometer. To remove silica nanoparticles introduced by the CMP step, the sample was cleaned using ultrasonic cleaners for 15 min. Graphene and hBN flakes were mechanically exfoliated from highly oriented graphite and hBN crystals, respectively. The hBN and graphene were stacked with the van der Waals assembly technique [2:CHF3:Ar (10:20:10) SCCM environment for 2 min to expose the graphene edge.Metal electrodes were fabricated via electron-beam evaporation and the lift-off of 5 nm Cr/50 nm Au.echnique ,46  with a fiber polarization controller to maximize the input power. The output power of the tunable laser was generally fixed at 1 mW, and the coupling efficiency of the gratings was approximately 8 dB. For the measurement of static characteristics, the output fiber was connected to a high-sensitivity power meter (THORLABS PM100). A DC signal was applied to two probes with a sourcemeter (KEITHLEY 2636B). For thermo-optic temporal response measurement, the output fiber was first connected to a photodetector (THORLABS PDA50B2) and then a real-time digital oscilloscope (YOKOGAWA DL6154). The RF signal was generated by an arbitrary waveform generator. The signal was split in the oscilloscope to monitor the source  platform with an hBN–graphene heterostructure, as illustrated in h enough . Correspm is the resonant order, the resonant wavelengths redshifted. As plotted in To verify the device’s thermal tunability, a DC bias was applied to the graphene using a sourcemeter through the pads. Since the resistance of graphene is higher than that of other parts of the electric circuit, the joule heating effect was mainly concentrated on the graphene. With the increment in voltage, the heat generated by graphene diffused into the core of the waveguide through the top silica layer. Consequently, the effective refractive index , and the incident wavelength was fixed at 1548 nm , the graphene part could not be photographed more clearly. Although we compensated for the emissivity of different materials via temperature correction before capturing, for low-emissivity materials, software emissivity compensation alone is susceptible to significant errors due to variation in surface emissivity and errors in the control temperature measurement process. To overcome this problem, the average temperature of the dashed area was calibrated with the Raman spectroscopy of graphene (see To show the tuning derived from the joule heating effect of graphene, hene see . As show3 solution [There are two methods to further improve the performance of a Fano resonator. First, the optical losses of monolayer graphene can be electrically or chemically suppressed by improving the Fermi level of graphene to Pauli blocking regions . Chemicasolution  could besolution . This heIn conclusion, we proposed and demonstrated low-power-consumption thermally tunable on-chip Fano resonators with graphene nanoheaters. The Fano resonators comprised an MRR and an especially designed scattering block, and are compact and easy to prepare. The graphene was laid on top of the planarized microring to act as a heating electrode. The fabricated Fano resonator showed energy consumption characteristics of down to ∼1 mW, and a spectral resolution as narrow as ∼0.05 nm. The low power consumption was mainly due to two aspects: the designed asymmetric line shape greatly reduced the required energy of state switching, and using graphene as the nanoheaters reduces the thickness of spacers that are required in conventional metal electrodes. Our results provide a promising building block for massive on-chip integrated devices, and may have applications in optical filters and switches.