Anion-Reinforced Solvation Structure Enables Stable Operation of Ether-Based Electrolyte in High-Voltage Potassium Metal Batteries.

Electrolytes with anion-dominated solvation are promising candidates to achieve dendrite-free and high-voltage potassium metal batteries. However, it's challenging to form anion-reinforced solvates at low salt concentrations. Herein, we construct an anion-reinforced solvation structure at a moderate concentration of 1.5 M with weakly coordinated cosolvent ethylene glycol dibutyl ether. The unique solvation structure accelerates the desolvation of K+, strengthens the oxidative stability to 4.94 V and facilitates the formation of inorganic-rich and stable electrode-electrolyte interface. These enable stable plating/stripping of K metal anode over 2200 h, high capacity retention of 83.0% after 150 cycles with a high cut-off voltage of 4.5 V in K0.67MnO2//K cells, and even 91.5% after 30 cycles under 4.7 V. This work provides insight into weakly coordinated cosolvent and opens new avenues for designing ether-based high-voltage electrolytes.

Religious/spiritual struggles and whole person functioning among Colombian university students: Longitudinal evidence of mutual influence.

This prospective study examined the primary, secondary and complex conceptual models of religious/spiritual struggles with 18 indicators of whole person functioning across five domains: psychological well-being, psychological distress, social well-being, physical well-being and character. We used three waves of longitudinal data (Wave 1: August/September 2021, Wave 2: October/November 2021, Wave 3: February 2022) from Colombian university students (N = 2878, Mage = 20.88 ± 4.05 years). Adjusting for covariates assessed in Wave 1, our primary analysis applied the analytic templates for outcome-wide and lagged exposure-wide designs to estimate two sets of lagged linear regression models. Religious/spiritual struggles in Wave 2 were associated with a small-to-medium-sized decline in subsequent functioning on 17/18 indicators in Wave 3, and worse functioning on 16/18 indicators in Wave 2 was associated with very small-to-medium-sized increases in subsequent religious/spiritual struggles in Wave 3. The results provided evidence in favour of the complex conceptual model for 16/18 indicators of whole person functioning. Our findings extend existing evidence on the reciprocal association between religious/spiritual struggles and individual functioning to a wide range of indicators, reinforcing the need for practitioners to consider the dynamic interplay between religious/spiritual struggles and individual functioning as they work with younger populations.

Deep Learning-Based Assessment of Built Environment From Satellite Images and Cardiometabolic Disease Prevalence.

Importance: Built environment plays an important role in development of cardiovascular disease. Large scale, pragmatic evaluation of built environment has been limited owing to scarce data and inconsistent data quality. Objective: To investigate the association between image-based built environment and the prevalence of cardiometabolic disease in urban cities. Design, Setting, and Participants: This cross-sectional study used features extracted from Google satellite images (GSI) to measure the built environment and link them with prevalence of cardiometabolic disease. Convolutional neural networks, light gradient-boosting machines, and activation maps were used to assess the association with health outcomes and identify feature associations with coronary heart disease (CHD), stroke, and chronic kidney disease (CKD). The study obtained aerial images from GSI covering census tracts in 7 cities (Cleveland, Ohio; Fremont, California; Kansas City, Missouri; Detroit, Michigan; Bellevue, Washington; Brownsville, Texas; and Denver, Colorado). The study used census tract-level data from the US Centers for Disease Control and Prevention's 500 Cities project. The data were originally collected from the Behavioral Risk Factor Surveillance System that surveyed people 18 years and older across the country. Analyses were conducted from February to December 2022. Exposures: GSI images of built environment and cardiometabolic disease prevalence. Main Outcomes and Measures: Census tract-level estimated prevalence of CHD, stroke, and CKD based on image-based built environment features. Results: The study obtained 31 786 aerial images from GSI covering 789 census tracts. Built environment features extracted from GSI using machine learning were associated with prevalence of CHD (R2 = 0.60), stroke (R2 = 0.65), and CKD (R2 = 0.64). The model performed better at distinguishing differences between cardiometabolic prevalence between cities than within cities (eg, highest within-city R2 = 0.39 vs between-city R2 = 0.64 for CKD). Addition of GSI features both outperformed and improved the model that only included age, sex, race, income, education, and composite indices for social determinants of health (R2 = 0.83 vs R2 = 0.76 for CHD; P <.001). Activation maps from the features revealed certain health-related built environment such as roads, highways, and railroads and recreational facilities such as amusement parks, arenas, and baseball parks. Conclusions and Relevance: In this cross-sectional study, a significant portion of cardiometabolic disease prevalence was associated with GSI-based built environment using convolutional neural networks.

Ten-year observation of corneal densitometry and associated factors following small incision lenticule extraction.

AIM: To investigate the long-term changes of corneal densitometry (CD) and its contributing elements after small incision lenticule extraction (SMILE). METHODS: Totally 31 eyes of 31 patients with mean spherical equivalent of -6.46±1.50 D and mean age 28.23±7.38y were enrolled. Full-scale examinations were conducted on all patients preoperatively and during follow-up. Visual acuity, manifest refraction, axial length, corneal thickness, corneal higher-order aberrations, and CD were evaluated. RESULTS: All surgeries were completed successfully without complications or adverse events. Ten-year safety index was 1.17±0.20 and efficacy 1.04±0.28. CD value of 0-6 mm zones in central layer was statistically significantly lower 10y postoperatively, compared with preoperative values (0-2 mmΔ=-1.62, 2-6 mmΔ=-1.24, P<0.01). There were no correlations between CD values and factors evaluated. CONCLUSION: SMILE is a safe and efficient procedure for myopia on a long-term basis. CD values get lower 10y postoperatively, whose mechanism is to be further discussed.

Summary of Outpatient Visits for Characteristic Nursing in Traditional Chinese Medicine.

The aim of this study was to investigate the practical outcomes of traditional Chinese medicine specialty nursing clinics in the clinical setting. Outpatient services have become increasingly popular for seeking medical care. Establishing traditional Chinese medicine specialty nursing clinics can meet the medical needs of the general public, and provide patients with convenient and efficient medical services. This study employed a retrospective cross-sectional observational design to analyze the medical service status of all patients who attended the clinic since its opening. Five qualified traditional Chinese medicine nursing experts identified and implemented 5 categories of traditional Chinese medicine characteristic nursing techniques, including cupping, moxibustion, needle acupuncture, and massage. Nurses and patients evaluated the treatment outcomes for various diseases. Since the establishment of the nursing outpatient department 2 years ago, there have been over 7046 visits, with a satisfaction rate of 97.1%. Currently, 5 nursing experts are nurturing a total of 11 graduate students, conducting 5 free clinics in the nursing outpatient department, and organizing 3 visits by overseas experts. The traditional Chinese medicine specialty nursing outpatient service effectively meets the diverse medical needs of patients, alleviates the outpatient pressure on hospitals, enhances the specialized development of nurses, increases the prominence of traditional Chinese medicine specialty nursing techniques, and promotes traditional Chinese medicine culture.

Universal Murray's law for optimised fluid transport in synthetic structures.

Materials following Murray's law are of significant interest due to their unique porous structure and optimal mass transfer ability. However, it is challenging to construct such biomimetic hierarchical channels with perfectly cylindrical pores in synthetic systems following the existing theory. Achieving superior mass transport capacity revealed by Murray's law in nanostructured materials has thus far remained out of reach. We propose a Universal Murray's law applicable to a wide range of hierarchical structures, shapes and generalised transfer processes. We experimentally demonstrate optimal flow of various fluids in hierarchically planar and tubular graphene aerogel structures to validate the proposed law. By adjusting the macroscopic pores in such aerogel-based gas sensors, we also show a significantly improved sensor response dynamics. In this work, we provide a solid framework for designing synthetic Murray materials with arbitrarily shaped channels for superior mass transfer capabilities, with future implications in catalysis, sensing and energy applications.

Chronic and Latent Viral Infections and Leukocyte Telomere Length across the Lifespan of Female and Male Individuals Living with or without HIV.

BACKGROUND: Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL). METHODS: Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and >60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling. RESULTS: The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3-4 viruses (vs. 0-2) was associated with a shorter LTL. CONCLUSIONS: Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.

Mapping Proximity to Infectious Disease Physicians Across the United States.

Enduring shortages of infectious disease physicians across the United States continue despite efforts to mitigate the problem. The recent fellowship match results underscore the difficulty in rectifying that shortage. Our report sheds light on the current geographic distribution of US infectious disease physicians and highlights the challenges faced by rural communities.

Lossy Mode Resonance Sensors Based on Anisotropic Few-Layer Black Phosphorus.

Lossy mode resonance (LMR) sensors offer a promising avenue to surpass the constraints of conventional surface plasmon resonance (SPR) sensors by delivering enhanced label-free detection capabilities. A notable edge of LMR over SPR is its excitation potential by both transverse electric (TE) and transverse magnetic (TM) polarized light. Yet this merit remains underexplored due to challenges to achieving high sensing performance under both TM and TE polarization within a singular LMR model. This study introduces a theoretical model for an LMR prism refractive index sensor based on a MgF2-few layer black phosphorus-MgF2 configuration, which can achieve angular sensitivity nearing 90° refractive index unit-1 (RIU-1) for both polarizations. Leveraging the distinct anisotropic nature of black phosphorus, the figure of merit (FOM) values along its two principal crystal axes (zigzag and armchair) show great difference, achieving an impressive FOM of 1.178 × 106 RIU-1 along the zigzag direction under TE polarized light and 1.231 × 104 RIU-1 along the armchair direction under TM polarized light. We also provide an analysis of the electric field distribution for each configuration at its respective resonant conditions. The proposed structure paves the way for innovative applications of anisotropic-material-based LMR sensors in various applications.

Protocol for the Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study: a prospective, observational, multicentre cohort study of acute spinal cord injury.

INTRODUCTION: Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues to grow rapidly, but there have been no large prospective cohort studies of patients with acute SCI. This proposed study aims to establish a multicentre, extensive sample cohort of clinical data and biological samples of patients in China, which would aid the systematisation and standardisation of clinical research and treatment of acute SCI, thus reducing the heavy burden of acute SCI on patients and society. METHODS AND ANALYSIS: The Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study is an observational, multicentre cohort study of patients with acute SCI admitted to the Qilu Hospital of Shandong University and other participating centres with prospective collection of their clinical data and biological samples. We aim to recruit 2097 patients in this study. Demographics, disease history, emergency intervention information, motor and sensory examinations, surgical information, medication information and rehabilitation evaluation will be recorded. This will facilitate the development of a prediction model for complications and prognosis of patients with acute SCI and an evaluation of the current management of acute SCI. Among these variables, detailed information on surgical treatment will also be used to assess procedures for acute SCI treatment. Outcome measurements, including the International Standard for Neurological Classification of Spinal Cord Injury examinations, the occurrence of complications and death, will be performed repeatedly during follow-up. We will analyse imaging data and blood samples to develop SCI imaging markers and biomarkers. ETHICS AND DISSEMINATION: This study protocol has been approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University and all other participating centres. The findings will be disseminated in peer-reviewed journals and academic conferences.

Integrated analysis of blood DNA methylation, genetic variants, circulating proteins, microRNAs, and kidney failure in type 1 diabetes.

Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5'-cytosine-phosphate-guanine-3' loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10-14. In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.

The anti-fatigue and sleep-aiding effects vary significantly among different recipes containing Ganoderma lucidum extracts.

Aims: This study aims to delve into the anti-fatigue and sleep-aiding effects of various formulations containing Ganoderma lucidum extracts. Materials and methods: PGB [incorporating Ganoderma lucidum extract (GE), broken Ganoderma lucidum spore powder (GB) and Paecilomyces hepiali mycelium (PH)] and GBS [composed of GE, GB, and Ganoderma sinense powder (GS)] were chosen as representative recipes for this study. Mice were treated with these recipes or key components of Ganoderma lucidum for 14 consecutive days. Subsequently, a weight-bearing swimming experiment was conducted to assess the mice's exhaustion time and evaluate the anti-fatigue properties of the recipes. Sleep-aiding effects were analyzed by measuring the sleep latency and duration. Furthermore, levels of blood lactic acid, serum urea nitrogen, hepatic glycogen, muscle glycogen, and malondialdehyde (MDA) were measured in the livers and muscles. Key findings: The anti-fatigue abilities of the tested mice were significantly improved after treatment with PGB and their sleep quality improved as well with GBS treatment. PGB treatment for 14 days could significantly prolong the exhaustion time in weight-bearing swimming (from 10.1 ± 0.5 min to 15.2 ± 1.3 min). Meanwhile, glycogen levels in the livers and muscles were significantly increased, while the levels of serum lactic acid, serum urea nitrogen, and MDA in the livers and muscles were significantly decreased. In contrast, mice treated with GBS for 14 days experienced significant improvements in sleep quality, with shortened sleep latency (from 6.8 ± 0.7 min to 4.2 ± 0.4 min), extended sleep duration (from 88.3 ± 1.4 min to 152.5 ± 9.3 min), and decreased muscle MDA levels. These results indicated that Ganoderma lucidum extracts can be used for anti-fatigue and or aid in sleeping, depending on how they are prepared and administered. Significance: This study provides experimental evidence and theoretical basis for the development of Ganoderma lucidum recipes that are specifically designed to help with anti-fatigue and sleep.

Unravelling the molecular landscape of endometrial cancer subtypes: insights from multi-omics analysis.

BACKGROUND: Endometrial cancer (EC) as one of the most common gynecologic malignancies is increasing in incidence during the past 10 years. Genome-Wide Association Studies (GWAS) extended to metabolic and protein phenotypes inspired us to employ multi-omics methods to analyze the causal relationships of plasma metabolites and proteins with EC to advance our understanding of EC biology and pave the way for more targeted approaches to its diagnosis and treatment by comparing the molecular profiles of different EC subtypes. METHODS: Two-sample Mendelian randomization (MR) was performed to investigate the effects of plasma metabolites and proteins on risks of different subtypes of EC (endometrioid and non-endometrioid). Pathway analysis, transcriptomic analysis, and network analysis were further employed to illustrate gene-protein-metabolites interactions underlying the pathogenesis of distinct EC histological types. RESULTS: We identified 66 causal relationships between plasma metabolites and endometrioid EC, and 132 causal relationships between plasma proteins and endometrioid EC. Additionally, 40 causal relationships between plasma metabolites and non-endometrioid EC, and 125 causal relationships between plasma proteins and non-endometrioid EC were observed. Substantial differences were observed between endometrioid and non-endometrioid histological types of EC at both the metabolite and protein levels. We identified 7 overlapping proteins (RGMA, NRXN2, EVA1C, SLC14A1, SLC6A14, SCUBE1, FGF8) in endometrioid subtype and 6 overlapping proteins (IL32, GRB7, L1CAM, CCL25, GGT2, PSG5) in non-endometrioid subtype and network analysis of above proteins and metabolites to identify coregulated nodes. CONCLUSIONS: Our findings observed substantial differences between endometrioid and non-endometrioid EC at the metabolite and protein levels, providing novel insights into gene-protein-metabolites interactions that could influence future EC treatments.

Short-term glycemic variability and intracranial atherosclerotic plaque stability assessed by high-resolution MR vessel wall imaging in type 2 diabetes mellitus.

OBJECTIVE: To investigate the relationship between short-term glycemic variability in patients with T2DM and the vulnerability of intracranial atherosclerotic plaques using HR-MR-VWI. MATERIALS AND METHODS: In total, 203 patients with acute ischemic stroke (AIS)/transient ischemia (TIA) combined with T2DM were enrolled. All of them underwent HR-MR-VWI during the period between July 2020 and July 2023. 203 patients were divided into groups with higher (1,5-AG≤ 30.7 µmol/L) and lower (1,5-AG> 30.7 µmol/L) short-term glycemic variability. Patients were also divided into the T1WI and non-T1WI hyperintensity groups. Associated factors(FBG, HbA1c, and 1,5-AG)for the T1WI hyperintensity were analyzed by binary logistic regression. We used the area under the curve (AUC), while the sensitivity and specificity were calculated at the optimal threshold. The Delong test was employed to compare the quality of the AUC of the predictors. RESULTS: The group with higher short-term glycemic variability had a higher incidence of the hyperintensity on T1WI, higher degree of enhancement, higher degree of stenosis and smaller lumen area (P < 0.05). The T1WI hyperintensity group had higher HbA1c levels, higher hemoglobin levels and lower 1,5-AG levels(P < 0.05). 1,5-AG (OR = 0.971, 95 % CI: 0.954∼0.988, P = 0.001), HbA1c (OR=1.305, 95 % CI: 1.065∼1.598, P = 0.01) and male sex (OR = 2.048, 95 % CI: 1.016∼4.128, P = 0.045)/(OR=2.102, 95 % CI: 1.058∼4.177, P = 0.034) were independent risk factors for the hyperintensity on T1WI. 1,5-AG demonstrated enhanced performance and yielded the highest AUC of the receiver operator characteristic curve (AUC = 0.726), with sensitivity and specificity values of 0.727 and 0.635 respectively. CONCLUSION: 1,5-AG, HbA1c and male sex are independent predictors of intracranial plaques with T1WI hyperintensity, the greater short-term glycemic variability, the higher incidence of vulnerable plaques.

Computational Study on Interlocked-Ferroelectricity-Contributed High-Performance Memristors Based on Two-Dimensional van der Waals Ferroelectric Semiconductors.

In order to realize the prevailing artificial intelligence technology, memristor-implemented in-memory or neuromorphic computing is highly expected to break the bottleneck of von Neumann computers. Although high-performance memristors have been vigorously developed in labs or in industry, systematic computational investigations on memristors are seldom. Hence, it is urgent to provide theoretical or computational support for the exploration of memristor operating mechanisms or the screening of memristor materials. Here, a computational method based on the main input parameters learned from the first-principles calculations was developed to measure resistance switching of two-terminal memristors with sandwiched metal/ferroelectric semiconductor/metal architectures, which strikingly agrees with the experimental measurements. Based on our developed method, the diverse multiterminal memristors were designed to fully exploit the application of interlocked ferroelectricity of a ferroelectric semiconductor and realize their heterosynaptic plasticity, and their heterosynaptic behaviors can still be well described. Our developed method can provide a paradigm for the emulation of ferroelectric memristors and inspire subsequent computational exploration. Furthermore, our study also supplies a device optimization strategy based on the interlocked ferroelectricity and easy processing of two-dimensional van der Waals ferroelectric semiconductors, and our proposed heterosynaptic memristors still await further experimental exploration.

Bulk Photovoltaic Effect Induced by Non-Covalent Interactions in Bilayered Hybrid Perovskite for Efficient Passive X-Ray Detection.

Hydrogen bonding as a multifunctional tool has always influenced the structure of hybrid perovskites. Compared with the research on hydrogen bonding, the study of halogen-halogen interactions on the structure and properties of hybrid perovskites is still in its early stages. Herein, a polar bilayered hybrid perovskite (IEA)2FAPb2I7 (IEA+ is 2-iodoethyl-1-ammonium, FA is formamidinium) with iodine-substituted spacer is successfully constructed by changing the configuration of interlayer cations and regulating non-covalent interactions at the organic-inorganic interface, which shows a shorter interlayer spacing and higher density (ρ = 3.862 g cm-3). The generation of structure polarity in (IEA)2FAPb2I7 is caused by the synergistic effect of hydrogen bonding and halogen-halogen interactions. Especially, as the length of the carbon chain in organic cations decreases, the I---I interaction in the system gradually strengthens, which may be the main reason for the symmetry-breaking. Polarity-induced bulk photovoltaics (Voc = 1.0 V) and higher density endow the device based on (I-EA)2FAPb2I7 exhibit a high sensitivity of 175.6 µC Gy-1 cm-2 and an ultralow detection limit of 60.4 nGy s-1 at 0 V bias under X-ray irradiation. The results present a facile approach for designing polar multifunctional hybrid perovskites, also providing useful assistance for future research on halogen-halogen interactions.

Geographic proximity to cardiovascular clinical trial sites: A National analysis in the United States.

INTRODUCTION: Suboptimal geographical access to cardiovascular clinical trial sites (CV-CTS) may be a cause of inadequate demographic representation in contemporary trials. Thus, we investigate access to CV-CTS in the US. METHODS: We obtained the location of CV-CTS from Clinicaltrials.gov. We calculated the distance in kilometers from each ZIP code to the nearest CV-CTS, stratifying our results based on urban/rural setting, sex and race. RESULTS: We identified a total of 10,506 studies in 4,630 US ZIP codes (10.5 %), of those only 237 (5 %) were rural. The overall median CV-CTS distance was 5.8 km (IQR: 2.7, 15.8). For urban residents, this distance was 4.5 km (IQR: 2.3, 9.2), while for rural residents, it was 24.2 km (IQR: 13.8, 42.2). RESULTS: We revealed important disparities involving geographical proximity to cardiovascular clinical trial sites. Increasing the representation of these populations in clinical trials is paramount to improving the applicability of their findings to real-world settings.

Clinical Features and Risk Factors for Drug-Induced Liver Injury: A Retrospective Study From China.

PURPOSE: With the prolongation of human life expectancy and the outbreak of COVID-19, antineoplastic agents, anti-infective drugs, and cardiovascular system drugs have been widely applied, resulting in a growing incidence of drug-induced liver injury (DILI) year by year. This study aimed to investigate signals, clinical characteristics, and risk factors in patients with liver injury. METHODS: A retrospective analysis was conducted on inpatients clinically diagnosed with DILI from 2019 to 2021 in one tertiary hospital in mainland China. The hepatic biochemical indices, clinical manifestations and suspected drugs of the patients were counted. We determined causality assessed by the Roussel Uclaf Causality Assessment Method in patients that the biochemistry met the diagnostic criteria recommended by the International Serious Adverse Events Consortium and compared them with contemporaneous patients diagnosed as DILI but with hepatic biochemical abnormalities only to identify the injure types and risk factors for DILI. FINDINGS: A total of 1167 patients from 2639 initial participants with DILI were included. According to the injured target cells, it can be divided into hepatocellular injury type 351 cases (30.08%), cholestatic injury type 97 cases (8.31%), mixed injury type 27 cases (2.31%), and biochemical abnormal only type 692 cases (59.30%). It involved 1738 cases of suspected drugs, 349 drugs, and the top 3 drug categories were antineoplastic agents, anti-infectives, and traditional Chinese medicines, with Cyclophosphamide, Atorvastatin, and Liuzasulfapyridine as the top 3 in order of ranking. The main symptoms of patients were darker urine, decreased appetite, and yellow sclera. The overall prognosis of patients with DILI was favorable, with 280 recovered cases (23.99%), 691 improved cases (59.21%), 189 not improved cases (16.20%), and 7 deaths (0.60%). There were significant differences in gender, age, malignancy, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, gamma-glutamyltransferase, albumin, international normalized ratio, and prognosis among patients with different injury types (P < 0.05). Multiple logistic regression analysis showed that female (odds ratio [OR] = 1.897, P < 0.001), alcohol use (OR = 1.905, P = 0.001), malignancy (OR = 0.417, P < 0.001), and pregnancy (OR = 0.201, P = 0.011) were independent factors influencing DILI. IMPLICATIONS: For most patients with liver injury, the manifestations are mild elevation of liver biochemistry without other symptoms (biochemical abnormal only type). The rest of the patients are predominantly of the hepatocellular injury type. Female and alcohol abuse patients are the risk factors of DILI, reminding clinicians to strengthen education on safe drug use, give individualized treatment, and regularly monitor liver function indexes in the patients.

StMAPKK5 responds to heat stress by regulating potato growth, photosynthesis, and antioxidant defenses.

Backgrounds: As a conserved signaling pathway, mitogen-activated protein kinase (MAPK) cascade regulates cellular signaling in response to abiotic stress. High temperature may contribute to a significant decrease in economic yield. However, research into the expression patterns of StMAPKK family genes under high temperature is limited and lacks experimental validation regarding their role in supporting potato plant growth. Methods: To trigger heat stress responses, potato plants were grown at 35°C. qRT-PCR was conducted to analyze the expression pattern of StMAPKK family genes in potato plants. Plant with StMAPKK5 loss-of-function and gain-of-function were developed. Potato growth and morphological features were assessed through measures of plant height, dry weight, and fresh weight. The antioxidant ability of StMAPKK5 was indicated by antioxidant enzyme activity and H2O2 content. Cell membrane integrity and permeability were suggested by relative electrical conductivity (REC), and contents of MDA and proline. Photosynthetic capacity was next determined. Further, mRNA expression of heat stress-responsive genes and antioxidant enzyme genes was examined. Results: In reaction to heat stress, the expression profiles of StMAPKK family genes were changed. The StMAPKK5 protein is located to the nucleus, cytoplasm and cytomembrane, playing a role in controlling the height and weight of potato plants under heat stress conditions. StMAPKK5 over-expression promoted photosynthesis and maintained cell membrane integrity, while inhibited transpiration and stomatal conductance under heat stress. Overexpression of StMAPKK5 triggered biochemical defenses in potato plant against heat stress, modulating the levels of H2O2, MDA and proline, as well as the antioxidant activities of CAT, SOD and POD. Overexpression of StMAPKK5 elicited genetic responses in potato plants to heat stress, affecting heat stress-responsive genes and genes encoding antioxidant enzymes. Conclusion: StMAPKK5 can improve the resilience of potato plants to heat stress-induced damage, offering a promising approach for engineering potatoes with enhanced adaptability to challenging heat stress conditions.

NANOG regulate the JAK/STAT3 pathway to promote trophoblast cell migration and epithelial-mesenchymal transition (EMT) in hypertensive disorders of pregnancy (HDP) through protein interaction with CDK1.

PROBLEM: Hypertensive disorders of pregnancy (HDP) are a common pregnancy disease. NANOG and Cyclin-dependent kinase 1 (CDK1) are essential for regulating the function of cell proliferation and apoptosis. However, the mechanism of action in HDP is yet unclear. METHOD: The microarray dataset GSE6573 was downloaded from the GEO database. Emt-related gene set was downloaded from Epithelial-Mesenchymal Transition gene database 2.0 were screened differentially expressed genes by bioinformatics analysis. Pathway Commons and Scansite 4.0 databases were used to predict the interaction between proteins. Placental tissue samples were collected from HDP patients and patients with uneventful pregnancies. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of NANOG, CDK1, MMP-2, MMP-9, EMT markers and the JAK/STAT3 pathway proteins. Transfection NANOG overexpression/knockdown, and CDK1 knockdown into the human chorionic trophoblast cells (HTR-8/Svneo). CCK-8, Transwell and Wound-healing assay were used to evaluate cell proliferation, invasion and migration. CO-IP and GST pull-down assays were used to confirm the protein interaction. RESULTS: A total obtained seven EMT-related differentially expressed genes, wherein NANOG, NODAL and LIN28A had protein interaction. In the HDP patients' tissue found that NANOG and CDK1 had lower expression. NANOG overexpression promoted HTR-8/Svneo proliferation, migration and EMT, while NANOG knockdown had the opposite effect. Further a protein interaction between STAT3 and CDK1 with NANOG. NANOG overexpression downregulated the JAK/STAT3 pathway to promote HTR-8/Svneo proliferation, migration and EMT, which was reversed by CDK1 knockdown. CONCLUSIONS: NANOG downregulated the JAK/STAT3 pathway to promote trophoblast cell proliferation, migration and EMT through protein interaction with CDK1.