Pulmonary neuroendocrine cells: crucial players in respiratory function and airway-nerve communication.

Pulmonary neuroendocrine cells (PNECs) are unique airway epithelial cells that blend neuronal and endocrine functions, acting as key sensors in the lung. They respond to environmental stimuli like allergens by releasing neuropeptides and neurotransmitters. PNECs stand out as the only lung epithelial cells innervated by neurons, suggesting a significant role in airway-nerve communication via direct neural pathways and hormone release. Pathological conditions such as asthma are linked to increased PNECs counts and elevated calcitonin gene-related peptide (CGRP) production, which may affect neuroprotection and brain function. CGRP is also associated with neurodegenerative diseases, including Parkinson's and Alzheimer's, potentially due to its influence on inflammation and cholinergic activity. Despite their low numbers, PNECs are crucial for a wide range of functions, highlighting the importance of further research. Advances in technology for producing and culturing human PNECs enable the exploration of new mechanisms and cell-specific responses to targeted therapies for PNEC-focused treatments.

Fitness costs, realized heritability, and mechanism of resistance to tenvermectin B in Plutella xylostella.

Tenvermectin B (TVM-B) and five TVM-B analogs were produced by fermentation of a genetically engineered strain Streptomyces avermitilis HU02, and TVM-B is being developed as a new insecticide. Through 11 generations of resistance selection against TVM-B in the diamondback moth, Plutella xylostella, the median lethal concentration (LC50) was increased from 14.84 to 1213.73 mg L-1. The resistance to TVM-B in P. xylostella developed fast and its realized heritability was high (h2 = 0.2901 (F7), h2 = 0.4070 (F11)). However, the relative fitness was 0.6916 suggesting a fitness cost in the resistant strains. The fitness cost was partially explained by the upregulation of the detoxification enzyme activity by 2.15 folds in carboxylate esterase (CarE) and the gene expressions of ATP-binding cassette transporter gene (ABCC2) and the alpha subunit of the glutamate-gated chloride channel (GluCl) by 1.70- and 2.32 folds, respectively. The resistance was also explained by two points of mutations at the alpha subunit of the glutamate-gated chloride channel in the P. xylostella (PxGluClα) subunit in F11. However, there was little change in the binding affinity. These results provided helpful information for the mechanism study of TVM-B resistance and will be conducive to designing rational resistance management strategies in P. xylostella.

Study on physical and mechanical properties of high-grade highway subgrade slate in permafrost region under freeze-thaw cycles.

The subgrade crushed-rocks of Gonghe-Yushu (Gongyu) Expressway in Qinghai Province are seriously weathered, resulting in a series of pavement diseases. Among the weathered crushed-rocks, the weathering degree of slate is particularly serious, and its physical and mechanical properties, weathering resistance and applicability are not clear. Therefore, this paper takes the slate in the subgrade crushed-rocks of Gongyu Expressway as the research object, and drills the core of the slate rock block to make a cylindrical standard sample, and uniaxial and triaxial compression tests, nuclear magnetic resonance tests, and electron probe micro-analysis tests were performed on it within 50 freeze-thaw cycles (FTC) under saturated conditions. According to the test results, the mass, longitudinal wave velocity, and strength of the slate specimens all decrease with the increase of the number of FTC, the cohesion ( C ) increases first and then decreases, and the change trend of internal friction angle (φ) is completely opposite to the cohesion. The FTC has an expansion effect on the pores of the slate specimens, and the microstructure of the rock particles on the specimen's surface is removed and becomes smooth. The results of mechanical tests are used in the Hoek-Brown (H-B) strength criterion, and a unified expression of the H-B criterion suitable for slate in permafrost regions is established. The above conclusions can provide some construction reference and maintenance of high-grade highways in cold regions.

Dietary magnesium intake and rheumatoid arthritis patients' all-cause mortality: evidence from the NHANES database.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with all-cause mortality increasing globally. Dietary magnesium (Mg), an anti-inflammatory nutrient, has been proven to be associated with the all-cause mortality. The association of dietary Mg intake and all-cause mortality in RA patients remains unknown. The aim of this study was to assess the association between dietary Mg intake and all-cause mortality in RA patients. METHODS: RA patients were extracted from the NHANES 1999-2018, and followed for survival through December 31, 2019. Dietary Mg intake data were obtained from 24-h dietary recall interview. The association between dietary Mg intake and RA patients' all-cause mortality was explored based on weighted univariate and multivariate Cox proportional hazard models and described as absolute risk difference (ARD), hazard ratios (HRs) and 95% confidence intervals (CIs). This association was further explored in subgroup analyses based on different age, gender and body mass index (BMI). RESULTS: Totally 2,952 patients were included. Until 31 December 2019, a total of 825 deaths were documented. RA patients with higher dietary Mg intake had a 11.12% reduction of all-cause mortality (ARD=-11.12%; HR = 0.74, 95%CI: 0.56-0.99) in the fully adjusted model, especially in female (HR = 0.68, 95%CI: 0.47-0.98), aged < 65 years (HR = 0.59, 95%CI: 0.37-0.94) and BMI ≤ 30 kg/m2 (HR = 0.62, 95%CI: 0.42-0.91). CONCLUSION: RA patients who consumed adequate dietary Mg from diet as well as supplements may had a lower risk of all-cause mortality.

Targeting MCL1 with Sanggenon C overcomes MCL1-driven adaptive chemoresistance via dysregulation of autophagy and endoplasmic reticulum stress in cervical cancer.

BACKGROUND: Cervical cancer ranks as one of the most prevalent malignancies among women worldwide and poses a significant threat to health and quality of life. MCL1 is an antiapoptotic protein closely linked to tumorigenesis, drug-resistance and poor prognosis in various cancers. Sanggenon C, a natural flavonoid derived from Morus albal., exhibits multiple activities, including anti-oxidant, anti-inflammatory, antivirus, and antitumor properties. However, the molecular mechanisms by which Sanggenon C exerts antitumor effects on in cervical cancer remain unclear. PURPOSE: To investigate the oncogenic role of MCL1 and elucidate the antitumor activity of Sanggenon C, along with its molecular mechanisms, in cervical cancer. METHODS: In vitro, the effects of Sanggenon C on proliferation, the cell cycle, apoptosis, and autophagy were explored. Transcriptome sequencing was employed to analyze critical genes and pathways. The expression of genes or proteins was evaluated via immunofluorescence, qRT-PCR, immunohistochemistry, and Western blotting. To identify targets of Sanggenon C, various techniques such as clinical database analysis, molecular docking, cellular thermal shift assays, co-immunoprecipitation, and ubiquitination assays were utilized. Additionally, Xenograft mouse models were established to further investigate Sanggenon C as a novel MCL1 inhibitor and its anti-tumor activity in vivo. RESULTS: Our investigation reveals that Sanggenon C effectively inhibits cervical cancer cell proliferation both in vitro and in vivo. Furthermore, Sanggenon C induces endoplasmic reticulum stress and triggers protective autophagy via activation of the ATF4-DDIT3-TRIB3-AKT-MTOR signaling axis. Furthermore, Sanggenon C specifically targets MCL1 to exert its antitumor effects by modulating MCL1 protein stability through SYVN1-mediated ubiquitination. Notably, MCL1 overexpression attenuates the Sanggenon C-induced decrease in cell viability and apoptosis. Our study further characterizes the role of MCL1 in cisplatin resistance and identifies MCL1 as a promising target for Sanggenon C, which effectively inhibits proliferation and induces apoptosis in cisplatin-resistant cervical cancer cells. Importantly, combining Sanggenon C with an autophagy inhibitor represents a promising strategy to enhance therapeutic outcomes in cisplatin-resistant cervical cancer cells. CONCLUSION: Our findings demonstrates that Sanggenon C induces endoplasmic reticulum stress and highlights the potential of targeting MCL1 to exploit vulnerabilities in drug-resistant cervical cancer cells. Sanggenon C emerges as a promising therapeutic agent against MCL1-driven adaptive chemoresistance through disruption of autophagy and endoplasmic reticulum stress in cervical cancer.

Shell-Core Microbeads Loaded with Probiotics: Influence of Lipid Melting Point on Probiotic Activity.

Probiotics have many beneficial physiological activities, but the poor stability during storage and gastrointestinal digestion limits their application. Therefore, in this study, a novel type of shell-core microbead for loading probiotics was prepared through high-precision concentric drop formation technology using gelatin as the shell material and lipids as the core material. The microbeads have a regular spherical structure, uniform size, low moisture content (<4%) and high probiotic activity (>9.0 log CFU/g). Textural testing showed that the hardness of the medium-chain triglyceride microbeads (MCTBs), cocoa butter replacer microbeads (CBRBs) and hydrogenated palm oil microbeads (HPOBs) increased gradually (319.65, 623.54, 711.41 g), but their springiness decreased (67.7, 43.3, 34.0%). Importantly, lipids with higher melting points contributed to the enhanced stability of probiotics during simulated digestion and storage. The viable probiotic counts of the HCTBs, CBRBs and HPOBs after being stored at 25 °C for 12 months were 8.01, 8.44, and 8.51 log CFU/g, respectively. In the simulated in vitro digestion process, the HPOBs resisted the destructive effects of digestive enzymes and gastric acid on probiotics, with a reduction in the probiotic viability of less than 1.5 log CFU/g. This study can provide new ideas for the preparation of intestinal delivery probiotic foods.

Detection technology and clinical applications of serum viral products of hepatitis B virus infection.

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.

Research Progress in the Degradation of Chemical Warfare Agent Simulants Using Metal-Organic Frameworks.

Chemical warfare agents primarily comprise organophosphorus nerve agents, saliva alkaloids, cyanides, and mustard gas. Exposure to these agents can result in severe respiratory effects, including spasms, edema, and increased secretions leading to breathing difficulties and suffocation. Protecting public safety and national security from such threats has become an urgent priority. Porous metal-organic framework (MOF) materials have emerged as promising candidates for the degradation of chemical warfare agents due to their large surface area, tunable pore size distribution, and excellent catalytic performance. Furthermore, combining MOFs with polymers can enhance their elasticity and processability and improve their degradation performance. In this review, we summarize the literature of the past five years on MOF-based composite materials and their effectiveness in degrading chemical warfare agents. Moreover, we discuss key factors influencing their degradation efficiency, such as MOF structure, pore size, and functionalization strategies. Furthermore, we highlight recent developments in the design of MOF-polymer composites, which offer enhanced degradation performance and stability for practical applications in CWA degradation. These composite materials exhibit good performance in degrading chemical warfare agents, playing a crucial role in protecting public safety and maintaining national security. We can expect to see more breakthroughs in the application of metal-organic framework porous materials for degrading chemical warfare agents. It is hoped that these innovative materials will play a positive role in achieving social stability and security.

Prediction of Acute Kidney Injury Following Isolated Coronary Artery Bypass Grafting in Heart Failure Patients with Preserved Ejection Fraction Using Machine Leaning with a Novel Nomogram.

Background: The incidence of postoperative acute kidney injury (AKI) is high due to insufficient perfusion in patients with heart failure. Heart failure patients with preserved ejection fraction (HFpEF) have strong heterogeneity, which can obtain more accurate results. There are few studies for predicting AKI after coronary artery bypass grafting (CABG) in HFpEF patients especially using machine learning methodology. Methods: Patients were recruited in this study from 2018 to 2022. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The machine learning methods adopted included logistic regression, random forest (RF), extreme gradient boosting (XGBoost), gaussian naive bayes (GNB), and light gradient boosting machine (LGBM). We used the receiver operating characteristic curve (ROC) to evaluate the performance of these models. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were utilized to compare the prediction model. Results: In our study, 417 (23.6%) patients developed AKI. Among the five models, random forest was the best predictor of AKI. The area under curve (AUC) value was 0.834 (95% confidence interval (CI) 0.80-0.86). The IDI and NRI was also better than the other models. Ejection fraction (EF), estimated glomerular filtration rate (eGFR), age, albumin (Alb), uric acid (UA), lactate dehydrogenase (LDH) were also significant risk factors in the random forest model. Conclusions: EF, eGFR, age, Alb, UA, LDH are independent risk factors for AKI in HFpEF patients after CABG using the random forest model. EF, eGFR, and Alb positively correlated with age; UA and LDH had a negative correlation. The application of machine learning can better predict the occurrence of AKI after CABG and may help to improve the prognosis of HFpEF patients.

Neuromodulatory Compensation of Cortical Neural Activity on Electrodeposited Pt/Ir Modified Microelectrode Arrays for Temperature Transients.

Temperature has a profound influence on various neuromodulation processes and has emerged as a focal point. However, the effects of acute environmental temperature fluctuations on cultured cortical networks have been inadequately elucidated. To bridge this gap, we have developed a brain-on-a-chip platform integrating cortical networks and electrodeposited Pt/Ir modified microelectrode arrays (MEAs) with 3D-printed bear-shaped triple chambers, facilitating control of temperature transients. This innovative system administers thermal stimuli while concurrently monitoring neuronal activity, including spikes and local field potentials, from 60 microelectrodes (diameter: 30 µm; impedance: 9.34 ± 1.37 kΩ; and phase delay: -45.26 ± 2.85°). Temperature transitions of approximately ±10 °C/s were applied to cortical networks on MEAs via in situ perfusion within the triple chambers. Subsequently, we examined the spatiotemporal dynamics of the brain-on-a-chip under temperature regulation at both the group level (neuronal population) and their interactions (network dynamics) and the individual level (cellular activity). Specifically, we found that after the temperature reduction neurons enhanced the overall information transmission efficiency of the network through synchronous firing to compensate for the decreased efficiency of single-cell level information transmission, in contrast to temperature elevation. By leveraging the integration of high-performance MEAs with perfusion chambers, this investigation provides a comprehensive understanding of the impact of temperature on the spatiotemporal dynamics of neural networks, thereby facilitating future exploration of the intricate interplay between temperature and brain function.

Initiating immunoglobulin replacement therapy helps reduce severe infections and shifts healthcare resource utilization to outpatient services among US patients with inborn errors of immunity.

AIMS: Patients with inborn errors of immunity (IEI) are predisposed to severe recurrent/chronic infections, and often require hospitalization, resulting in substantial burden to patients/healthcare systems. While immunoglobulin replacement therapies (IgRTs) are the standard first-line treatment for most forms of IEI, limited real-world data exist regarding clinical characteristics and treatment costs for patients with IEI initiating such treatment. This retrospective analysis examined infection and treatment characteristics in US patients with IEI initiating IgRT with immune globulin infusion (human), 10% (IG10%). Healthcare resource utilization (HCRU) and associated costs before and after treatment initiation were compared. Additionally, the impact of COVID-19 on infection diagnoses was evaluated. METHODS: Patients with IEI initiating IG10% between July 2012 and August 2019 were selected from Merative MarketScan Databases using diagnosis/prescription codes. Patients were followed 6 months before and after first IG10% claim date. Demographic and clinical characteristics were described. Treatment characteristics and HCRU before and after IG10% initiation were compared. Infection diagnoses during 2020 and 2019 (March-December) were compared. RESULTS: The study included 1,497 patients with IEI diagnoses (mean age = 43.4 years) initiating IG10%, with frequently reported comorbidities like asthma (32.1%). Following IG10% initiation, fewer severe infection diagnoses (11.6% vs 19.9%), fewer infection-related inpatient (10.8% vs 19.5%) and outpatient services (71.6% vs 79.9%), and lower infection-related total healthcare costs ($7,849 vs $13,995; p < 0.001)-driven by lower inpatient costs ($2,746 vs $9,900)-were observed than before. Fewer patients had infection diagnoses during COVID-19 (22.8%) than the prior year (31.2%). CONCLUSION: Patients with IEI are susceptible to severe infections leading to high disease burden and treatment costs. Following IG10% initiation, we observed fewer infections, lower infection-related treatment costs, and shift in care (inpatient to outpatient) leading to significant cost savings. Among patients with IEI, 27% fewer infection diagnoses were observed during the early COVID-19 lockdown period than the prior year.

Some people are born with inborn errors of immunity, or IEI. This study included 1,497 people with IEI who recently started taking a drug called immunoglobulin therapy. Before taking this drug, the participants got infections easily, were hospitalized often, and had to take other costly medicines. After starting this drug, they had fewer infections and could be treated at the doctor's office. They had fewer infections during the COVID-19 pandemic than before the pandemic.

Investigating Communication Dynamics in Neuronal Network using 3D Gold Microelectrode Arrays.

Although in vitro neuronal network models hold great potential for advancing neuroscience research, with the capacity to provide fundamental insights into mechanisms underlying neuronal functions, the dynamics of cell communication within such networks remain poorly understood. Here, we develop a customizable, polymer modified three-dimensional gold microelectrode array with sufficient stability for high signal-to-noise, long-term, neuronal recording of cultured networks. By using directed spatial and temporal patterns of electrical stimulation of cells to explore synaptic-based communication, we monitored cell network dynamics over 3 weeks, quantifying communication capability using correlation heatmaps and mutual information networks. Analysis of synaptic delay and signal speed between cells enabled us to establish a communication connectivity model. We anticipate that our discoveries of the dynamic changes in communication across the neuronal network will provide a valuable tool for future studies in understanding health and disease as well as in developing effective platforms for evaluating therapies.

Application of biomimetic nanovaccines in cancer immunotherapy: A useful strategy to help combat immunotherapy resistance.

Breakthroughs in actual clinical applications have begun through vaccine-based cancer immunotherapy, which uses the body's immune system, both humoral and cellular, to attack malignant cells and fight diseases. However, conventional vaccine approaches still face multiple challenges eliciting effective antigen-specific immune responses, resulting in immunotherapy resistance. In recent years, biomimetic nanovaccines have emerged as a promising alternative to conventional vaccine approaches by incorporating the natural structure of various biological entities, such as cells, viruses, and bacteria. Biomimetic nanovaccines offer the benefit of targeted antigen-presenting cell (APC) delivery, improved antigen/adjuvant loading, and biocompatibility, thereby improving the sensitivity of immunotherapy. This review presents a comprehensive overview of several kinds of biomimetic nanovaccines in anticancer immune response, including cell membrane-coated nanovaccines, self-assembling protein-based nanovaccines, extracellular vesicle-based nanovaccines, natural ligand-modified nanovaccines, artificial antigen-presenting cells-based nanovaccines and liposome-based nanovaccines. We also discuss the perspectives and challenges associated with the clinical translation of emerging biomimetic nanovaccine platforms for sensitizing cancer cells to immunotherapy.

A General Strategy Based on Hetero-Charge Coupling Effect for Constructing Single-Atom Sites.

Single-atom catalysts have emerged as cutting-edge hotspots in the field of material science owing to their excellent catalytic performance brought about by well-defined metal single-atom sites (M SASs). However, huge challenges still lie in achieving the rational design and precise synthesis of M SASs. Herein, we report a novel synthesis strategy based on the hetero-charge coupling effect (HCCE) to prepare M SASs loaded on N and S co-doped porous carbon (M1/NSC). The proposed strategy was widely applied to prepare 17 types of M1/NSC composed of single or multi-metal with the integrated regulation of the coordination environment and electronic structure, exhibiting good universality and flexible adjustability. Furthermore, this strategy provided a low-cost method of efficiently synthesizing M1/NSC with high yields, that can produce more than 50 g catalyst at one time, which is key to large-scale production. Among various as-prepared unary M1/NSC (M can be Fe, Co, Ni, V, Cr, Mn, Mo, Pd, W, Re, Ir, Pt, or Bi) catalysts, Fe1/NSC delivered excellent performance for electrocatalytic nitrate reduction to NH3 with high NH3 Faradaic efficiency of 86.6 % and high NH3 yield rate of 1.50 mg h-1 mgcat. -1 at -0.6 V vs. RHE. Even using Fe1/NSC as a cathode in a Zn-nitrate battery, it exhibited a high open circuit voltage of 1.756 V and high energy density of 4.42 mW cm-2 with good cycling stability.

Prediction of prognosis in patients with systemic sclerosis based on a machine-learning model.

OBJECTIVE: The clinical manifestations of systemic sclerosis (SSc) are highly variable, resulting in varied outcomes and complications. Diverse fibrosis of the skin and internal organs, vasculopathy, and dysregulated immune system lead to poor and varied prognoses in patients with SSc subtypes. Therefore, this study aimed to develop a personalized tool for predicting the prognosis of patients with SSc. METHODS: A cohort of 517 patients with SSc were recruited between January 2009 and November 2021 at Xijing Hospital in China, and 266 patients completed the follow-up and performed in the survival analysis. Risk factors for death were identified using Cox survival analysis and random survival forest-based machine-learning methods separately. The consistency index, area under the curve (AUC), and integrated Brier scores were used to compare the predictive performance of the different prognostic models. RESULTS: The results of Cox-based multivariate regression analysis suggested that pulmonary arterial hypertension, digital ulcer, and Modified Rodnan Skin Score (mRSS) were independent risk factors for poor prognosis in patients with SSc and significant risk factors in random survival forest (RSF) surveys. A nomogram was plotted to evaluate the prognostic risk to facilitate clinical assessment; the RSF model had better predictive performance than the Cox model, with 3- and 5-year AUCs of 0.74 and 0.78, respectively. CONCLUSION: Machine-learning models can help us better understand the prognosis of patients with SSc and comprehensively evaluate the clinical characteristics of each individual. The early identification of the characteristics of high-risk patients can improve the prognosis of those with SSc. Key Points • Regarding predictive performance, the random survival forest model was more effective than the Cox model and had unique advantages in analyzing nonlinear effects and variable importance. • Machine learning using the simple clinical features of patients with systemic sclerosis (SSc) to predict mortality can guide attending physicians, and the early identification of high-risk patients with SSc and referral to experts will assist rheumatologists in monitoring and management planning.

A Near-Infrared Fluorescent Probe with Large Stokes Shift for Sensitive Detection of Hydrogen Sulfide in Environmental Water, Food Spoilage, and Biological Systems.

Hydrogen sulfide (H2S) is an important endogenous gas transmitter that plays a critical role in various physiological and pathological processes and can also cause a negative impact on foodstuffs. In this study, we designed and synthesized a simple, easily available, high-yield, and low-cost near-infrared (λem = 710 nm) fluorescent probe, DEM-H2S, with a substantial Stokes shift (205 nm) for the detection of H2S. DEM-H2S features high selectivity and sensitivity (LOD = 80 nM) toward H2S, accompanied by a noticeable color change. Upon interaction with H2S, DEM-H2S exhibits a restored ICT (Intramolecular Charge Transfer) process, thereby manifesting near-infrared fluorescence. DEM-H2S has been successfully utilized to detect H2S in actual water samples and to monitor the spoilage of food items, such as pork, shrimp, and eggs. Furthermore, DEM-H2S enables the imaging of endogenous and exogenous H2S in living MCF-7 cells and zebrafish. Hence, DEM-H2S provides an attractive method for the detection of H2S in environmental, food, and biological systems, holding potential value in physiological and pathological research.

CD147 regulates the formation and function of immune synapses.

CD147 is a T cell activation-associated molecule which is closely involved in the formation of the immune synapse (IS). However, the precise role of CD147 in T cell activation and IS formation remains unclear. In the present study, we demonstrated that CD147 translocated to the IS upon T cell activation and was primarily distributed in the peripheral super molecular cluster (p-SMAC). The knock down of CD147 expression in T cells, but not in B cells, impaired IS formation. CD147 participated in IS formation between T cells and different types of antigen-presenting cells (APCs), including macrophages and dendritic cells. Ligation of CD147 with its monoclonal antibody (mAb) HAb18 effectively inhibited T cell activation and IL-2 secretion. CD98, a critical molecule interacting with CD147, was distributed in IS in a CD147-dependent way. Phosphorylation levels of T cell receptor (TCR) related molecules, like ZAP-70, ERK, and cJun, were down-regulated by CD147 ligation, which is crucial for the interaction of CD147 and TCR signaling transduction. CD147 is indispensable for the formation of immune synapses and plays an important role in the regulation of its function.

Thermostable Bacterial Collagenolytic Proteases: A Review.

Collagenolytic proteases are widely used in the food, medical, pharmaceutical, cosmetic, and textile industries. Mesophilic collagenases exhibit collagenolytic activity under physiological conditions, but have limitations in efficiently degrading collagen-rich wastes, such as collagen from fish scales, at high temperatures due to their poor thermostability. Bacterial collagenolytic proteases are members of various proteinase families, including the bacterial collagenolytic metalloproteinase M9 and the bacterial collagenolytic serine proteinase families S1, S8, and S53. Notably, the C-terminal domains of collagenolytic proteases, such as the pre-peptidase C-terminal domain, the polycystic kidney disease-like domain, the collagen-binding domain, the proprotein convertase domain, and the ß-jelly roll domain, exhibit collagen-binding or -swelling activity. These activities can induce conformational changes in collagen or the enzyme active sites, thereby enhancing the collagen-degrading efficiency. In addition, thermostable bacterial collagenolytic proteases can function at high temperatures, which increases their degradation efficiency since heat-denatured collagen is more susceptible to proteolysis and minimizes the risk of microbial contamination. To date, only a few thermophile-derived collagenolytic proteases have been characterized. TSS, a thermostable and halotolerant subtilisin-like serine collagenolytic protease, exhibits high collagenolytic activity at 60°C. In this review, we present and summarize the current research on A) the classification and nomenclature of thermostable and mesophilic collagenolytic proteases derived from diverse microorganisms, and B) the functional roles of their C-terminal domains. Furthermore, we analyze the cleavage specificity of the thermostable collagenolytic proteases within each family and comprehensively discuss the thermostable collagenolytic protease TSS.

High-Performance Bidirectional Microelectrode Array for Assessing Sevoflurane Anesthesia Effects and In Situ Electrical Stimulation in Deep Brain Regions.

Precise assessment of wakefulness states during sevoflurane anesthesia and timely arousal are of paramount importance to refine the control of anesthesia. To tackle this issue, a bidirectional implantable microelectrode array (MEA) is designed with the capability to detect electrophysiological signal and perform in situ deep brain stimulation (DBS) within the dorsomedial hypothalamus (DMH) of mice. The MEA, modified with platinum nanoparticles/IrOx nanocomposites, exhibits exceptional characteristics, featuring low impedance, minimal phase delay, substantial charge storage capacity, high double-layer capacitance, and longer in vivo lifetime, thereby enhancing the sensitivity of spike firing detection and electrical stimulation (ES) effectiveness. Using this MEA, sevoflurane-inhibited neurons and sevoflurane-excited neurons, together with changes in the oscillation characteristics of the local field potential within the DMH, are revealed as indicative markers of arousal states. During the arousal period, varying-frequency ESs are applied to the DMH, eliciting distinct arousal effects. Through in situ detection and stimulation, the disparity between these outcomes can be attributed to the influence of DBS on different neurons. These advancements may further our understanding of neural circuits and their potential applications in clinical contexts.

NSUN2 mediates distinct pathways to regulate enterovirus 71 replication.

Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine (m5C) modifications on viral RNAs, which are essential for the replication of various viruses. Despite the function of m5C deposition is well characterized, other potential roles of NSUN2 in regulating viral replication remain largely unknown. In this study, the m5C modified residues catalyzed by NSUN2 on enterovirus 71 (EV71) RNAs were mapped. NSUN2, along with m5C modifications, played multiple roles during the EV71 life cycle. Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs. Additionally, NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination. Furthermore, both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated. Taken together, this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication, and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.