Thermoplastic PHB-Reinforced Chitosan Piezoelectric Films for Biodegradable Pressure Sensors.

Flexible and wearable pressure sensors have attracted significant attention in the fields of smart medicine and human health monitoring. Nevertheless, the design and fabrication of degradable disposable pressure sensors still face urgent challenges. Herein, we fabricated poly(3-hydroxybutyrate) (PHB)-reinforced chitosan (CS) piezoelectric films for intelligent sensors through a simple, low-cost, and environmentally friendly roll-forming method. The results show that PHB doping successfully increased the effective piezoelectric coefficient of the chitosan-based film from 40.12 to 49.38 pm/V (a 23% increase). Simultaneously, the pressure sensor based on the CS/PHB film exhibited excellent response sensitivity (484 mV/kPa) and a wide linear response range (0-130 kPa), which could be used as haptic sensors and motion monitoring sensors for the fast response to human motion signals. Additionally, the CS/PHB film could be completely degraded within 18 days in a natural soil environment, demonstrating outstanding degradability. Therefore, chitosan-based piezoelectric films with excellent biodegradability and piezoelectric characteristics have been successfully fabricated in this work, which will promote the innovative development of green chitosan-based electronic devices and disposable pressure sensors.

Unveiling the causal relationship between circulating levels of micronutrients and risk of facial aging: A Mendelian randomization study.

Facial aging involves a continuous sequence of complex, interrelated events that impact numerous facial tissues. The aim of the study was to elucidate the casual relationship between circulating micronutrients and risk of facial aging. A two-sample Mendelian randomization analysis was performed using genetic data from genome-wide association studies. The inverse-variance weighted method is used for causal effect estimation, and additional tools such as Mendelian randomization-Egger, weighted median, simple mode, and weighted mode were used to refine the analysis. We conducted an in-depth examination of the correlation between several micronutrient blood levels and the risk of facial aging, and identified 3 key micronutrients (selenium, carotene, and iron) that may have a significant impact on skin health. Inverse-variance weighted results indicate that selenium levels were positively correlated with the risk of facial aging (odds ratio [OR] 1.005, P = .027), while a negative causal effect of carotene (OR 0.979, P = .024) and iron (OR 0.976, P = .009) on age-related facial alterations was observed. This study offers a new and insightful perspective on the current understanding of antiaging strategies, particularly the importance of appropriate consumption of essential micronutrients to maintain healthy skin condition.

The value of metagenomic next-generation sequencing with different nucleic acid extracting methods of cell-free DNA or whole-cell DNA in the diagnosis of non-neutropenic pulmonary aspergillosis.

Purpose: Metagenomic next-generation sequencing(mNGS) is a novel molecular diagnostic technique. For nucleic acid extraction methods, both whole-cell DNA (wcDNA) and cell-free DNA (cfDNA) are widely applied with the sample of bronchoalveolar lavage fluid (BALF). We aim to evaluate the clinical value of mNGS with cfDNA and mNGS with wcDNA for the detection of BALF pathogens in non-neutropenic pulmonary aspergillosis. Methods: mNGS with BALF-cfDNA, BALF-wcDNA and conventional microbiological tests (CMTs) were performed in suspected non-neutropenic pulmonary aspergillosis. The diagnostic value of different assays for pulmonary aspergillosis was compared. Results: BALF-mNGS (cfDNA, wcDNA) outperformed CMTs in terms of microorganisms detection. Receiver operating characteristic (ROC) analysis indicated BALF-mNGS (cfDNA, wcDNA) was superior to culture and BALF-GM. Combination diagnosis of either positive for BALF-mNGS (cfDNA, wcDNA) or CMTs is more sensitive than CMTs alone in the diagnosis of pulmonary aspergillosis (BALF-cfDNA+CMTs/BALF-wcDNA+CMTs vs. CMTs: ROC analysis: 0.813 vs.0.66, P=0.0142/0.796 vs.0.66, P=0.0244; Sensitivity: 89.47% vs. 47.37%, P=0.008/84.21% vs. 47.37%, P=0.016). BALF-cfDNA showed a significantly greater reads per million (RPM) than BALF-wcDNA. The area under the ROC curve (AUC) for RPM of Aspergillus detected by BALF-cfDNA, used to predict "True positive" pulmonary aspergillosis patients, was 0.779, with a cut-off value greater than 4.5. Conclusion: We propose that the incorporation of BALF-mNGS (cfDNA, wcDNA) with CMTs improves diagnostic precision in the identification of non-neutropenic pulmonary aspergillosis when compared to CMTs alone. BALF-cfDNA outperforms BALF-wcDNA in clinical value.

Efficiency enhancement in Aspergillus niger α-L-rhamnosidase reverse hydrolysis by using a tunnel site rational design strategy.

There has been ongoing interest in improving the efficiency of glycoside hydrolase for synthesizing glycoside compounds through protein engineering, given the potential applications of glycoside compounds. In this study, a strategy of modifying the substrate access tunnel was proposed to enhance the efficiency of reverse hydrolysis catalyzed by Aspergillus niger α-L-rhamnosidase. Analysis of the tunnel dynamics identified Tyr299 as a key modifiable residue in the substrate access tunnel. The location of Tyr299 was near the enzyme surface and at the outermost end of the substrate access tunnel, suggested its role in substrate recognition and throughput. Based on the properties of side chains, six mutants were designed and expressed by Pichia pastoris. Compared to WT, the reverse hydrolysis efficiencies of mutants Y299P and Y299W were increased by 21.3 % and 11.1 %, respectively. The calculation results of binding free energy showed that the binding free energy was inversely proportional to the reverse hydrolysis efficiency. Further, when binding free energy levels were comparable, the mutants with shorter side chains displayed a higher reverse hydrolysis efficiency. These results proved that substrate access tunnel modification was an effective method to improve the reverse hydrolysis efficacy of α-L-rhamnosidase and also provided new insights for modifying other glycoside hydrolases.

Tear Fluid Progranulin as a Noninvasive Biomarker for the Monitoring of Corneal Innervation Changes in Patients With Type 2 Diabetes Mellitus.

Purpose: This study aimed to investigate the expression levels of progranulin (PGRN) in the tears of patients with diabetic retinopathy (DR) versus healthy controls. Additionally, we sought to explore the correlation between PGRN levels and the severity of ocular surface complications in patients with diabetes. Methods: In this prospective, single-visit, cross-sectional study, patients with DR (n = 48) and age-matched healthy controls (n = 22) were included and underwent dry eye examinations. Tear fluid was collected, and its components were analyzed using the Luminex assay. The subbasal nerve plexus of all participants was evaluated by in vivo confocal microscopy. Results: Patients with DR exhibited more severe dry eye symptoms, along with a reduction in nerve fiber density, length, and branch density within the subbasal nerve plexus, accompanied by an increase in the number of dendritic cells. Tear PGRN levels were also significantly lower in patients with diabetes than in normal controls, and the levels of some inflammatory factors (TNF-α, IL-6, and MMP-9) were higher in patients with DR. Remarkably, the PGRN level significantly correlated with nerve fiber density (R = 0.48, P < 0.001), nerve fiber length (R = 0.65, P < 0.001), and nerve branch density (R = 0.69, P < 0.001). Conclusions: Tear PGRN levels might reflect morphological changes in the corneal nerve plexus under diabetic conditions, suggesting that PGRN itself is a reliable indicator for predicting the advancement of neurotrophic keratopathy in patients with diabetes. Translational Relevance: PGRN insufficiency on the ocular surface under diabetic conditions was found to be closely associated with nerve impairment, providing a novel perspective to discover the pathogenesis of diabetic complications, which could help in developing innovative therapeutic strategies.

Filter-Free UV Photodetectors Based on Unipolar Barrier Van der Waals α-In2Se3/h-BN Heterostructures.

Visible-blind ultraviolet (UV) light detection has a wide application range in scenes like space environment monitoring and medical imaging. To realize miniaturized UV detectors with high performance and high integration ability, new device structures without bulky light filters need to be developed based on advanced mechanisms. Here the unipolar barrier van der Waals heterostructure (UB-vdWH) photodetector is reported that realizes filter-free visible-blind UV detection with good stability, robustness, selectivity, and high detection performance. The UB-vdWH shows a responsivity of 2452 A W-1, a photo on-off ratio of 2.94 × 105 and a detectivity of 1.26 × 1015 Jones as a UV detector, owing to the intentionally designed barrier height that suppresses dark current and photoresponse to visible light during the transport process. The good performance remains intact during 104 test cycles or even under high temperatures, which proves the stability, and robustness of the UB-vdWH, thus shows the huge potential for a wider application range.

[Research on Characterization and Biocompatibility of 3D Printed Ti-6Al-4V Pelvic Prosthesis].

The treatment of bone defects caused by fractures or bone tissue lesions has always been a difficult problem in the field of orthopedics. Implantation of high-performance titanium alloy prosthesis is an effective method to treat bone defects. 3D printing technology can produce low-modulus titanium alloy implants with porous structures, providing a better solution to the above problems. This technology is convenient to design and has a huge advantage in making orthopedic implants. The article used electron beam melting in 3D printing technology to create two samples of Ti-6Al-4V prosthesis, including solid structural pelvic prosthesis and porous structural pelvic prosthesis. The mechanical properties of the prosthesis showed that the yield and tensile strengths of the rod tensile specimen were 894 MPa and 956 MPa, respectively, and the compressive modulus and compressive strength of the porous pelvic prosthesis were 55 GPa and 65.2 MPa, respectively. The results of the L929 cytotoxicity assay and the MC3T3-E1 cell adhesion assay demonstrated good biocompatibility of the prosthetic samples. New Zealand white rabbits were used to prepare the femoral joint cavity defect models and two pelvic prostheses were implanted. A microscopic CT scan 4 weeks after implantation showed that the bone defect caused by the drill had healed and that the porous structure of the pelvic prosthesis formed a new trabecular structure within the hole. In conclusion, the 3D printed Ti-6Al-4V pelvic prosthesis has excellent mechanical properties, biocompatibility, and the ability to promote new bone growth.

PBOX-sRNA-seq uncovers novel features of miRNA modification and identifies selected 5'-tRNA fragments bearing 2'-O-modification.

The concomitant cloning of RNA degradation products is a major concern in standard small RNA-sequencing practices. This not only complicates the characterization of bona fide sRNAs but also hampers cross-batch experimental replicability and sometimes even results in library construction failure. Given that all types of plant canonical small RNAs possess the 3' end 2'-O-methylation modification, a new small RNA sequencing (sRNA-seq) method, designated as PBOX-sRNA-seq, has been developed specifically to capture this modification. PBOX-sRNA-seq, as its name implies, relies on the sequential treatment of RNA samples with phenylboronic acid-polyacrylamide gel electrophoresis (PBA-PAGE) and sodium periodate (NaIO4) oxidation, before sRNA library construction and sequencing. PBOX-sRNA-seq outperformed separate treatments (i.e. PBA-PAGE only or NaIO4 only) in terms of the depletion of unmethylated RNA species and capture 2'-O-modified sRNAs with extra-high purity. Using PBOX-sRNA-seq, we discovered that nascent miRNA-5p/-3p duplexes may undergo mono-cytidylation/uridylation before 2'-O-methylation. We also identified two highly conserved types of 5'-tRNA fragments (tRF) bearing HEN1-independent 2'-O modification (mainly the 13-nt tRF-5aAla and the 26-nt tRF-5bGly). We believe that PBOX-sRNA-seq is powerful for both qualitative and quantitative analyses of sRNAs in plants and piRNAs in animals.

A Reconfigurable Bipolar Image Sensor for High-Efficiency Dynamic Vision Recognition.

Dynamic vision perception and processing (DVPP) is in high demand by booming edge artificial intelligence. However, existing imaging systems suffer from low efficiency or low compatibility with advanced machine vision techniques. Here, we propose a reconfigurable bipolar image sensor (RBIS) for in-sensor DVPP based on a two-dimensional WSe2/GeSe heterostructure device. Owing to the gate-tunable and reversible built-in electric field, its photoresponse shows bipolarity as being positive or negative. High-efficiency DVPP incorporating front-end RBIS and back-end CNN is then demonstrated. It shows a high recognition accuracy of over 94.9% on the derived DVS128 data set and requires much fewer neural network parameters than that without RBIS. Moreover, we demonstrate an optimized device with a vertically stacked structure and a stable nonvolatile bipolarity, which enables more efficient DVPP hardware. Our work demonstrates the potential of fabricating DVPP devices with a simple structure, high efficiency, and outputs compatible with advanced algorithms.

A phosphate transporter in VIPergic neurons of the suprachiasmatic nucleus gates locomotor activity during the light/dark transition in mice.

The suprachiasmatic nucleus (SCN) encodes time of day through changes in daily firing; however, the molecular mechanisms by which the SCN times behavior are not fully understood. To identify factors that could encode day/night differences in activity, we combine patch-clamp recordings and single-cell sequencing of individual SCN neurons in mice. We identify PiT2, a phosphate transporter, as being upregulated in a population of Vip+Nms+ SCN neurons at night. Although nocturnal and typically showing a peak of activity at lights off, mice lacking PiT2 (PiT2-/-) do not reach the activity level seen in wild-type mice during the light/dark transition. PiT2 loss leads to increased SCN neuronal firing and broad changes in SCN protein phosphorylation. PiT2-/- mice display a deficit in seasonal entrainment when moving from a simulated short summer to longer winter nights. This suggests that PiT2 is responsible for timing activity and is a driver of SCN plasticity allowing seasonal entrainment.

Effect of Intrinsic Ferroelectric Phase Transition on Hydrogen Evolution Electrocatalysis.

Heterogeneous electrocatalysis closely relies on the electronic structure of the catalytic materials. The ferroelectric-to-paraelectric phase transition of the materials also involves a change in the state of electrons that could impact the electrocatalytic activity, but such correlation remains unexplored. Here, we demonstrate experimentally and theoretically that the intrinsic electrocatalytic activity could be regulated as exampled by hydrogen evolution reaction catalysis over two-dimensional ferroelectric CuInP2S6. The obvious discontinuity in the overpotential and apparent activation energy values for CuInP2S6 electrode are illustrated during the ferroelectric-to-paraelectric phase transition caused by copper displacement around Tc point (318 K), revealing the ferroelectro-catalytic effect on thermodynamics and kinetics of electrocatalysis. When loading Pt single atom on the CuInP2S6, the paraelectric phase one showed an improved hydrogen evolution activity with smaller apparent activation energy over the ferroelectric phase counterpart. This is attributed to the copper hopping between two sulfur planes, which alternate between strong and weak H adsorption at the Pt sites to simultaneously promote H+ reactant adsorption and H2 product desorption.

Monkeypox Virus Crosstalk with HIV: An Integrated Skin Transcriptome and Machine Learning Study.

The emergence of the monkeypox virus (MPXV) outbreak presents a formidable challenge to human health. Emerging evidence suggests that individuals with HIV have been disproportionately affected by MPXV, with adverse clinical outcomes and higher mortality rates. However, the shared molecular mechanisms underlying MPXV and HIV remain elusive. We identified differentially expressed genes (DEGs) from two public data sets, GSE219036 and GSE184320, and extracted common DEGs between MPXV and HIV. We further performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interactions (PPI), candidate drug assessment, and immune correlation of hub genes analysis. We validated the key biomarkers using multiple machine learning (ML) methods including random forest (RF), t-distributed stochastic neighbor embedding (tSNE), and uniform manifold approximation and projection (UMAP). A total of 59 common DEGs were identified between MPXV and HIV. Our functional analysis highlighted multiple pathways, including the ERK cascade, NF-κB signaling, and various immune responses, playing a collaborative role in the progression of both diseases. The PPI and gene co-expression networks were constructed, and five key genes with significant immune correlations were identified and validated by multiple ML models, including SPRED1, SPHK1, ATF3, AKT3, and AKT1S1. Our study emphasizes the common pathogenesis of HIV and MPXV and highlights the pivotal genes and shared pathways, providing new opportunities for evidence-based management strategies in HIV patients co-infected with MPXV.

Exploration of the common pathogenic link between COVID-19 and diabetic foot ulcers: An in silico approach.

Background and Aims: The Coronavirus Disease-19 (COVID-19) is posing an ongoing threat to human health. Patients of diabetic foot ulcer (DFU) are susceptible to COVID-19-induced adverse outcomes. Nevertheless, investigations into their mutual molecular mechanisms have been limited to date. In the present work, we tried to uncover the shared pathogenesis and regulatory gene targets of COVID-19 and DFU. Methods: In this study, we chose GSE161281 as the COVID-19 data set, which contained severe acute respiratory syndrome coronavirus 2 infected human induced embryonic stem cell-derived peripheral neurons (n = 2) with uninfected controls (n = 2). The GSE134431 designated as the DFU data set, comprising full-thickness DFU (n = 13) and diabetic foot skin (n = 8) samples from diabetic patients. The differential expressed genes (DEGs) were identified from GSE161281 and GSE134431, and the common DEGs between COVID-19 and DFU were extracted. Multifactor regulatory network and co-expression network of the common DEGs were analyzed, along with candidate drug prediction. Results: Altogether, six common DEGs (dickkopf-related protein 1 [DKK1], serine proteinase inhibitor A3 [SERPINA3], ras homolog family member D [RHOD], myelin protein zero like 3 [MPZL3], Claudin-11 [CLDN11], and epidermal growth factor receptor pathway substrate 8-like 1 [EPS8L1]) were found between COVID-19 and DFU. Functional analyses indicated that pathways of apoptotic and Wnt signaling may contribute to progression of COVID-19. Gene co-expression network implied the shared pathways of immune regulation and cytokine response participated collectively in the development of DFU and COVID-19. A multifactor regulatory network was constructed integrating the corresponding microRNAs (miRNAs) and transcription factors. Additionally, we proposed potential drug objects for the combined therapy. Conclusion: Our study revealed the shared molecular mechanisms underlying COVID-19 and DFU. The identified pivotal targets and common pathways can provide new perspectives for further research and assist the development of management strategies in patients of DFU complicated with COVID-19.

Genetic evidence implicating circulating lipids and lipid drug targets in pterygium.

There is limited knowledge about the impact of circulating lipids and lipid-modifying drugs on pterygium development, with conflicting results reported. Our study aimed to address these questions by applying the Mendelian randomization (MR) approach. A two-step MR model was developed. In the first step, bidirectional two-sample MR was employed to establish the causal relationship between circulating lipids and pterygium risk. In the second step, drug-target MR analysis was conducted to assess the causal effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors on pterygium outcomes. Genetically predicted low-density lipoprotein cholesterol (LDL-c) levels were found to be significantly associated with an increased risk of pterygium (Inverse variance weighted [IVW] odds ratio [OR] = 2.227; P = 1.53 × 10-4). Similarly, higher total cholesterol (TC) levels exhibited a suggestive association with greater susceptibility to pterygium (IVW OR = 1.806; P = 1.70 × 10-3). Through drug-target MR, a positive causal association was noted between HMGCR-mediated LDL-c levels and pterygium (IVW OR = 6.999; P = 0.016), suggesting that statins may be effective in reducing pterygium risk. The present findings suggest that circulating TC and LDL-c are risk factors for pterygium. Additionally, the results indicate that HMGCR inhibitors, which lower LDL-c levels, have a potential protective effect on pterygium outcomes. Further research is warranted to elucidate the underlying mechanisms involved in pterygium pathogenesis, with a particular focus on cholesterol metabolism.

Integrated multi-omics and machine learning approach reveals lipid metabolic biomarkers and signaling in age-related meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) is a prevalent inflammatory disorder of the ocular surface that significantly impacts patients' vision and quality of life. The underlying mechanism of aging and MGD remains largely uncharacterized. The aim of this work is to investigate lipid metabolic alterations in age-related MGD (ARMGD) through integrated proteomics, lipidomics and machine learning (ML) approach. For this purpose, we collected samples of female mouse meibomian glands (MGs) dissected from eyelids at age two months (n = 9) and two years (n = 9) for proteomic and lipidomic profilings using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. To further identify ARMGD-related lipid biomarkers, ML model was established using the least absolute shrinkage and selection operator (LASSO) algorithm. For proteomic profiling, 375 differentially expressed proteins were detected. Functional analyses indicated the leading role of cholesterol biosynthesis in the aging process of MGs. Several proteins were proposed as potential biomarkers, including lanosterol synthase (Lss), 24-dehydrocholesterol reductase (Dhcr24), and farnesyl diphosphate farnesyl transferase 1 (Fdft1). Concomitantly, lipidomic analysis unveiled 47 lipid species that were differentially expressed and clustered into four classes. The most notable age-related alterations involved a decline in cholesteryl esters (ChE) levels and an increase in triradylglycerols (TG) levels, accompanied by significant differences in their lipid unsaturation patterns. Through ML construction, it was confirmed that ChE(26:0), ChE(26:1), and ChE(30:1) represent the most promising diagnostic molecules. The present study identified essential proteins, lipids, and signaling pathways in age-related MGD (ARMGD), providing a reference landscape to facilitate novel strategies for the disease transformation.

Social equity perception and public mental health: a Chinese study with panel data.

BACKGROUND: Mental health is a vital part of an individual's overall health and well-being, and the relationship between society and individuals has always been a focus of academic and public attention. However, the effect of social equity perceptions on individual mental health remains unclear. METHODS: Data were collected from 8,922 survey respondents with an average age of 47.533 years from the China Labor-force Dynamics Survey 2016 and 2018. The Center for Epidemiological Studies Depression scale was used to assess mental health. A two-way fixed effects regression model was used to determine the association between social equity perception and individual mental health. RESULTS: Individuals with higher perceptions of social equity were more likely to report better mental health ([Formula: see text] = -0.944, p < 0.01). Happiness, life satisfaction, and social trust partially play mediating roles in the relationship between social equity perception and individual mental health, while education and age play moderating roles. CONCLUSION: Social equity perception is a vital factor that affects mental health. Public policies should focus on helping less educated and older people improve their social equity perception to improve their mental health.

Engineering Atomic-Scale Patterning and Resistive Switching in 2D Crystals and Application in Image Processing.

The ultrathin thickness of 2D layered materials affords the control of their properties through defects, surface modification, and electrostatic fields more efficiently compared with bulk architecture. In particular, patterning design, such as moiré superlattice patterns and spatially periodic dielectric structures, are demonstrated to possess the ability to precisely control the local atomic and electronic environment at large scale, thus providing extra degrees of freedom to realize tailored material properties and device functionality. Here, the scalable atomic-scale patterning in superionic cuprous telluride by using the bonding difference at nonequivalent copper sites is reported. Moreover, benefitting from the natural coupling of ordered and disordered sublattices, controllable piezoelectricity-like multilevel switching and bipolar switching with the designed crystal structure and electrical contact is realized, and their application in image enhancement is demonstrated. This work extends the known classes of patternable crystals and atomic switching devices, and ushers in a frontier for image processing with memristors.

A Wearable Electrochemical Sensor Based on Anti-Fouling and Self-Healing Polypeptide Complex Hydrogels for Sweat Monitoring.

Although continuous monitoring of constituents in complex sweat is crucial for noninvasive physiological evaluation, biofouling on the sweat sensor surface and inadequate flexible self-healing materials restrict its applications. Herein, a fully self-healing and strong anti-biofouling polypeptide complex hydrogel (AuNPs/MoS2/Pep hydrogel) with excellent electrochemical performances was created. The anti-fouling electrochemical sweat sensor was fabricated based on the AuNPs/MoS2/Pep hydrogel to address these issues. It was found that the polypeptide hydrogel was designed to form a network structure and carried abundant hydrophilic groups, resulting in a AuNPs/MoS2/Pep hydrogel with superior anti-biofouling properties in sweat for 30 min and even long-term stability in undiluted human sweat. In addition, SEM, TEM, UV, XPS, and infrared spectrogram demonstrated that the binding force of π-π stacking force between MoS2 and naphthalene groups in the designed peptide endowed the polypeptide complex hydrogel with an excellent self-healing property. Furthermore, the polypeptide complex hydrogel preserved wearable device function of continuously monitoring uric acid (UA) and ascorbic acid (AA) in sweat in situ. This novel fabricated sweat sensor with high anti-biofouling ability, excellent self-healing property, and sensitive and selective analytical capability describes a new opportunity for health monitoring in situ.

Crosstalk between TRPV1 and immune regulation in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is the leading indication for corneal transplantation worldwide. Our aim was to investigate the role of transient receptor potential vanilloid subtype 1 (TRPV1) and the associated immune regulation contributing to this pathological condition. Significant upregulation of TRPV1 was detected in the H2O2-induced in vitro FECD model. Based on gene expression microarray dataset GSE142538 and in vitro results, a comprehensive immune landscape was studied and a negative correlation was found between TRPV1 with different immune cells, especially regulatory T cells (Tregs). Functional analyses of the 313 TRPV1-related differentially expressed genes (DEGs) revealed the involvement of TRP-regulated calcium transport, as well as inflammatory and immune pathways. Four TRPV1-related core genes (MAPK14, GNB1, GNAQ, and ARRB2) were screened, validated by microarray dataset GSE112039 and the combined validation dataset E-GEAD-399 & 564, and verified by in vitro experiments. Our study suggested a potential crosstalk between TRPV1 and immune regulation contributing to FECD pathogenesis. The identified pivotal biomarkers and immune-related pathways provide a novel framework for future mechanistic and therapeutic studies of FECD.

A wearable sensor based on multifunctional conductive hydrogel for simultaneous accurate pH and tyrosine monitoring in sweat.

Flexible and wearable sweat sensors have drawn extensive attention by virtue of their continuous and real-time monitoring of molecular level information. However, current sweat-based sensors still pose several challenges, such as low accuracy for analytes detection, susceptibility to microorganism and poor mechanical performance. Herein, we demonstrated a noninvasive wearable sweat sensing patch composed of an electrochemical sensing system, and a pilocarpine-based iontophoretic system to stimulate sweat secretion. The electrochemical sensor based on tannic acid-Ag-carbon nanotube-polyaniline (TA-Ag-CNT-PANI) composite hydrogel was designed for on-body detection of pH and tyrosine (Tyr), a disease marker associated with multiple disorders, such as tyrosinemia and bulimia nervosa. The wearable sweat sensor can not only monitor the pH and Tyr in sweat simultaneously, but also further calibrate Tyr detection results with the measured pH value, so as to eliminate the effect of Tyr response variance at different pH and enhance the accuracy of the sensor. Furthermore, the presence of tannic acid chelated-Ag nanoparticles (TA-Ag NPs) and carbon nanotubes (CNTs) significantly improved the conductivity and flexibility of the hydrogel and endowed the composite hydrogel with antibacterial capability. Of note, the constructed wearable sensor was capable of monitoring Tyr with enhanced accuracy in various sweats.