Two three-dimensional coordination polymers as fluorescence probes for the detection of nitrobenzene, tetracycline, fluazinam and their application in green pepper.

Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.

An Invasion Risk Assessment of Alien Woody Species in Potential National Park Sites in Xinjiang, China, Under Climate Change.

The invasion of alien woody species may have broad ecological, economic, and health impacts on ecosystems and biodiversity under climate change. Previous studies showed that disrupting the biodiversity conservation mechanisms in protected areas can seriously threaten natural ecosystems and the protection of rare and endangered species in such protected areas. However, there is currently no standard for evaluating the invasion risk of woody plants under climate change when establishing national parks in China. Therefore, we used a species distribution model to evaluate the invasion risk of 250 invasive alien woody species in potential national park sites in Xinjiang under climate change. The results indicated that the probability of forest invasion in the potential Altai Kanas National Park was determined to be significantly higher than that of the average level in Xinjiang nature reserves, both under current and future climate conditions. At the same time, the probability of invasive woody species invading coniferous forests, broad-leaved forests, and grassland ecosystems is higher in the Altai Kanas and Tianshan potential national parks. We found that Acer negundo, Robinia pseudoacacia, and Amorpha fruticose in potential parks in Xinjiang have higher invasion potential and thus require heightened vigilance to stop their spread. This study contributes to the monitoring and management of national parks and provides an actionable foundation for protecting ecosystem functions and minimizing the potential risk of invasive alien species under climate change.

Population pharmacokinetic study in children with vascular anomalies: body weight as a key variable in predicting the initial dose and dosing frequency of sirolimus.

Background: The main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus. Methods: A PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations (C trough) of 5-15 ng/mL. Results: In total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance (CL) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BW of 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of <10, 10-20, 20-40, and ≥40 kg, respectively; for a once-daily regimen, the recommended doses were 0.06, 0.07, 0.08, and 0.09 mg/kg/day for BW of <10, 10-30, 30-50, and ≥50 kg, respectively. Notably, sirolimus C trough could be maintained between 5-15 ng/mL across various dosing frequencies based on the recommended dosing regimen. Conclusion: We established a PPK model of sirolimus for children with VAs and proposed an initial dosing strategy. Integrating initial dose and medication frequency recommendations into sirolimus' guidelines will broaden its clinical options and simplify the clinical management for childhood VAs.

Osteoprotective effect of Achyranthes bidentata root extract on osteoporotic rats: a systematic review and meta-analysis.

CONTEXT: Achyranthes bidentata Blume (ABB), a plant of Amaranthaceae family, has been one of the more commonly used phytomedicine remedies for thousands of years, and recent studies have highlighted the efficacy of its extracts in the treatment of osteoporosis. Nonetheless, a thorough analysis of its benefits is currently absent. OBJECTIVE: This meta-analysis assessed the effects of ABB root extract (ABBRE) on osteoporotic rats and provides a rationale for future clinical studies. METHODS: Searches were conducted in seven different Chinese and English databases, and the search period was from their establishment to January 2024. This study was registered in PROSPERO (CRD42023418917). Selected research regarding the ABBRE treatment of osteoporotic rats, and the corresponding research has distinctly reported outcomes, and the data on the bone mineral density (BMD), bone histomorphometrics, biomechanical parameters, and bone biochemical markers of osteoporotic rats can be extracted. RESULTS: Through screening, 11 studies met the eligibility requirements for inclusion, in which 222 animals were studied. The treatment group with ABBRE exhibited increased bone mineral density (standardized mean difference [SMD] = 1.64, 95% CI = 0.52 to 2.77). Based on subgroup analysis, the greatest increase in bone mineral density was observed when the dose of ABBRE was ≤ 400 mg/kg/day and the duration of treatment was ≤ 12 weeks. CONCLUSIONS: ABBRE is a phytomedicine that can effectively promote the enhancement of bone mineral density and ease osteoporosis. It can be developed into a new alternative therapy by conducting experiments and clinical studies on larger samples.

Characterization of stem cell landscape and assessing the stemness degree to aid clinical therapeutics in hematologic malignancies.

Hematological malignancies are a group of cancers that affect the blood, bone marrow, and lymphatic system. Cancer stem cells (CSCs) are believed to be responsible for the initiation, progression, and relapse of hematological malignancies. However, identifying and targeting CSCs presents many challenges. We aimed to develop a stemness index (HSCsi) to identify and guide the therapy targeting CSCs in hematological malignancies. We developed a novel one-class logistic regression (OCLR) algorithm to identify transcriptomic feature sets related to stemness in hematologic malignancies. We used the HSCsi to measure the stemness degree of leukemia stem cells (LSCs) and correlate it with clinical outcomes.We analyze the correlation of HSCsi with genes and pathways involved in drug resistance and immune microenvironment of acute myeloid leukemia (AML). HSCsi revealed stemness-related biological mechanisms in hematologic malignancies and effectively identify LSCs. The index also predicted survival and relapse rates of various hematologic malignancies. We also identified potential drugs and interventions targeting cancer stem cells (CSCs) of hematologic malignancies by the index. Moreover, we found a correlation between stemness and bone marrow immune microenvironment in AML. Our study provides a novel method and tool to assess the stemness degree of hematologic malignancies and its implications for clinical outcomes and therapeutic strategies. Our HSC stemness index can facilitate the precise stratification of hematologic malignancies, suggest possible targeted and immunotherapy options, and guide the selection of patients.

Risk perception and quality of working life of nurses in infectious disease department in China: The chain-mediating effects of psychological resilience and social support.

AIM: To determine whether social support and psychological resiliency are significant mediators of the associations between risk perception and quality of working life in Chinese nurses working with infectious diseases. DESIGN: A cross-sectional study. METHODS: A cross-sectional survey of 879 nurses in infectious diseases department of specialty or general hospitals in China completed online questionnaires on the nurses' risk perception questionnaire, quality of working life, psychological resilience and the social support rating scale. RESULTS: Our study observed that risk perception directly negatively influences the quality of working life of infectious disease nurses, while psychological resilience and social support positively chain mediate this relationship. CONCLUSION: Critical elements impacting the quality of working life of infectious disease nurses are risk perception, psychological resilience and social support. Managers may think about decreasing the level of risk perception and enhancing the quality of working life of infectious disease nurses by enhancing their psychological resilience and providing support. PUBLIC CONTRIBUTION: The quality of working life of infectious disease nurses should be a priority for nursing management; it is critical to maintain their health and well-being, raise the quality of care and lower turnover. Managers should create resilience-building programmes and support tools to assist nurses properly perceive risks and adopt protective strategies to deal with them to improve the quality of working life for nurses.

CYP2C19 genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of trough lacosamide concentration or clinical response.

Background: The widespread clinical use of lacosamide (LCM) has revealed significant individual differences in clinical response, with various reported influencing factors. However, it remains unclear how genetic factors related to the disposition and clinical response of LCM, as well as drug-drug interactions (DDIs), exert their influence on pediatric patients with epilepsy. Objectives: To evaluate the impact of genetic variations and DDIs on plasma LCM concentrations and clinical response. Design: Patients with epilepsy treated with LCM from June 2021 to March 2023 in the Children's Hospital of Nanjing Medical University were included in the analysis. Methods: The demographic information and laboratory examination data were obtained from the hospital information system. For the pharmacogenetic study, the left-over blood specimens, collected for routine plasma LCM concentration monitoring, were used to perform genotyping analysis for the selected 26 single nucleotide polymorphisms from 14 genes. The trough concentration/daily dose (C 0/D) ratio and efficacy outcomes were compared. Results: Patients achieved 90.1% and 68.9% responder rates in LCM mono- and add-on therapy, respectively. The genetic variant in the CYP2C19 *2 (rs4244285) was associated with a better responsive treatment outcome (odds ratio: 1.82; 95% confidence interval: 1.05-3.15; p = 0.031). In monotherapy, 36% of patients were CYP2C19 normal metabolizers (NMs), 49% were intermediate metabolizers (IMs), and 15% were poor metabolizers (PMs) carrying CYP2C19 *2 or *3. Of note, the C 0/D ratios of IMs and PMs were 9.1% and 39.6% higher than those of NMs, respectively. Similar results were in the add-on therapy group, and we also observed a substantial decrease in the C 0/D ratio when patients were concomitant with sodium channel blockers (SCBs). Conclusion: This study was the first to confirm that CYP2C19 *2 or *3 variants impact the disposition and treatment response of LCM in children with epilepsy. Moreover, concomitant with SCBs, particularly oxcarbazepine, also decreased plasma LCM concentration.

CYP2C19 genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of plasma lacosamide concentration or treatment efficacy This study examined the impact of genetic factors and drug combinations on the effectiveness and plasma concentrations of lacosamide, an antiseizure medication, in patients under 18. Analyzing blood samples from 316 patients at the Children's Hospital of Nanjing Medical University, researchers discovered that genetic variations in the CYP2C19 (i.e. *2 and *3), along with metabolic capacity, and co-medication with sodium channel blockers, all influence plasma lacosamide concentration. Understanding these genetic influences could inform personalized dosing strategies, improving the medication's management for pediatric epilepsy patients.

Comparison of bloodstream infections due to Corynebacterium striatum, MRSA, and MRSE.

BACKGROUND: Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aims to investigate the clinical features and outcomes of C. striatum-BSI. METHODS: We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified them into C. striatum-BSI group and contamination group; Clinical characteristics, treatments, and outcomes were compared between the C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI. RESULTS: Fifty-three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to the contaminated group, the C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0 h vs. 42.5 h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 h) when compared to both the MRSA (20 h) and MRSE groups (19 h) (p < 0.05). Appropriate therapy within 24 h of BSI onset was significantly lower in the C. striatum group (28%) compared to the MRSA (64.5%) and MRSE (65.9%) groups (p < 0.005). The 28-day mortality was higher in the C. striatum group (52.0%) compared to the MRSA (25.8%) and MRSE (18.2%) groups.  CONCLUSIONS: Given the distinct characteristics of C. striatum-BSI, including a longer time to positivity than other Gram-positive bacteria and higher mortality rates, we suggest prescribing early appropriate antibiotics if C. striatum-BSI is suspected.

A national-wide survey on clinical implementation of PGx testing into precision therapeutics for Chinese children: a long way before standard clinical practice.

BACKGROUND: Pharmacogenetics/pharmacogenomics (PGx) focuses on the genetic variation that causes the heterogeneity of pharmacokinetics and drug response among individuals and has the potential to predict individual efficacy and/or side effects. This study aims to investigate and understand the implementation of genetic testing for the personalized medication (GTPM) in children's hospitals in Mainland China. METHODS: A survey was conducted on 50 children's hospitals from 31 provinces, municipalities, and autonomous regions across Mainland China, and statistical analysis and recommendations were made. RESULTS: Questionnaire response was rate of 76.0% (38/50). Data from 15 hospitals conducting GTPM were included in this study, but only 6 hospitals had offered PGx tests for no less than five drug-related genes, and only 5 hospitals had covered more than ten drugs, which was a small scale overall. 20.0% of the laboratories did not conduct internal quality control, and 33.3% did not participate in inter-laboratory quality assessment. 46.7% of the practitioners did not receive external training. The primary goal for GTPM was to optimize drug dosage in the 15 hospitals, while the main challenge for GTPM was the implementation cost. CONCLUSION: Although GTPM in pediatrics has made major progress in Mainland China in recent years, there were still various problems in terms of software, hardware configuration, personnel allocation, business scale, quality control, and result interpretation. This requires joint efforts of health administration, medical insurance departments, researchers, and hospitals to promote and improve GTPM.

Complete synchronization of discrete-time fractional-order BAM neural networks with leakage and discrete delays.

This paper concerns complete synchronization (CS) problem of discrete-time fractional-order BAM neural networks (BAMNNs) with leakage and discrete delays. Firstly, on the basis of Caputo fractional difference theory and nabla l-Laplace transform, two equations about the nabla sum are strictly proved. Secondly, two extended Halanay inequalities that are suitable for discrete-time fractional difference inequations with arbitrary initial time and multiple types of delays are introduced. In addition, through applying Caputo fractional difference theory and combining with inequalities gained from this paper, some sufficient CS criteria of discrete-time fractional-order BAMNNs with leakage and discrete delays are established under adaptive controller. Finally, one numerical simulation is utilized to certify the effectiveness of the obtained theoretical results.

Oxalate-derived porous C-doped NiO with amorphous-crystalline heterophase for supercapacitors.

Constructing amorphous/crystalline heterophase structure with high porosity is a promising strategy to effectively tailor the physicochemical properties of electrode materials and further improve the electrochemical performance of supercapacitors. Here, the porous C-doped NiO (C-NiO) with amorphous/crystalline heterophase grown on NF was prepared using NF as Ni source via a self-sacrificial template method. Calcining the self-sacrificial NiC2O4 template at a suitable temperature (400 °C) was beneficial to the formation of porous heterophase structure with abundant cavities and cracks, resulting in high electrical conductivity and rich ion/electron-transport channels. The density functional theory (DFT) calculations further verified that in-situ C-doping could modulate the electronic structure and enhance the OH- adsorption capability. The unique porous amorphous/crystalline heterophase structure greatly accelerated electrons/ions transfer and Faradaic reaction kinetic, which effectively improved the charge storage. The C-NiO calcined at 400 °C (C-NiO(400)) displayed a markedly enhanced specific charge, outstanding rate property and excellent cycling stability. Furthermore, the hybrid supercapacitor assembled by C-NiO(400) and active carbon achieved a high energy density of 49.0 Wh kg-1 at 800 W kg-1 and excellent cycle stability (90.9 % retention at 5 A/g after 10 000 cycles). This work provided a new strategy for designing amorphous/crystalline heterophase electrode materials in high-performance energy storage.

Benzo(a)pyrene exposure during pregnancy leads to germ cell apoptosis in male mice offspring via affecting histone modifications and oxidative stress levels.

Infertility has gradually become a global health concern, and evidence suggests that exposure to environmental endocrine-disrupting chemicals (EDCs) represent one of the key causes of infertility. Benzo(a)pyrene (BaP) is a typical EDC that is widespread in the environment. Previous studies have detected BaP in human urine, semen, cervical mucus, oocytes and follicular fluid, resulting in reduced fertility and irreversible reproductive damage. However, the mechanisms underlying the effects of gestational BaP exposure on offspring fertility in male mice have not been fully explored. In this study, pregnant mice were administered BaP at doses of 0, 5, 10 and 20 mg/kg/day via gavage from Days 7.5 to 12.5 of gestation. The results revealed that BaP exposure during pregnancy disrupted the structural integrity of testicular tissue, causing a disorganized arrangement of spermatogenic cells, compromised sperm quality, elevated levels of histone modifications and increased apoptosis in the testicular tissue of F1 male mice. Furthermore, oxidative stress was also increased in the testicular tissue of F1 male mice. BaP activated the AhR/ERα signaling pathway, affected H3K4me3 expression and induced apoptosis in testicular tissue. AhR and Cyp1a1 were overexpressed, and the expression of key molecules in the antioxidant pathway, including Keap1 and Nrf2, was reduced. The combined effects of these molecules led to apoptosis in testicular tissues, damaging and compromising sperm quality. This impairment in testicular cells further contributed to compromised testicular tissues, ultimately impacting the reproductive health of F1 male mice.

One step toward precision dosing of caffeine in preterm infants: An external evaluation of published population pharmacokinetic models.

BACKGROUND: Several population pharmacokinetic (PopPK) models of caffeine in preterm infants have been published, but the extrapolation of these models to facilitate model-informed precision dosing (MIPD) in clinical practice is uncertain. This study aimed to comprehensively evaluate their predictive performance using an external, independent dataset. METHODS: Data used for external evaluation were based on an independent cohort of preterm infants. Currently available PopPK models for caffeine in preterm infants were identified and re-established. Prediction- and simulation-based diagnostics were used to assess model predictability. The influence of prior information was assessed using Bayesian forecasting. RESULTS: 120 plasma samples from 76 preterm infants were included in the evaluation dataset. Twelve PopPK models of caffeine in preterm infants were re-established based on our previously published study. Although two models showed superior predictive performance, none of the 12 PopPK models met all the clinical acceptance criteria of these external evaluation items. Besides, the external predictive performances of most models were unsatisfactory in prediction- and simulation-based diagnostics. Nevertheless, the application of Bayesian forecasting significantly improved the predictive performance, even with only one prior observation. CONCLUSIONS: Two models that included the most covariates had the best predictive performance across all external assessments. Inclusion of different covariates, heterogeneity of preterm infant characteristics, and different study designs influenced predictive performance. Thorough evaluation is needed before these PopPK models can be implemented in clinical practice. The implementation of MIPD for caffeine in preterm infants could benefit from the combination of PopPK models and Bayesian forecasting as a helpful tool.

Puerarin Alleviates Blood Pressure via Inhibition of ROS/TLR4/NLRP3 Inflammasome Signaling Pathway in the Hypothalamic Paraventricular Nucleus of Salt-Induced Prehypertensive Rats.

BACKGROUND: Puerarin is an isoflavone compound isolated from the roots of a leguminous plant, the wild kudzu. Various functional activities of this compound in multiple diseases have been reported. However, the effect and mechanism of puerarin in improving blood pressure remain non-elucidated. PURPOSE: The current study was designed to assess the preventive effects of puerarin on the onset and progression of hypertension and to verify the hypothesis that puerarin alleviates blood pressure by inhibiting the ROS/TLR4/NLRP3 inflammasome signaling pathway in the hypothalamic paraventricular nucleus (PVN) of salt-induced prehypertensive rats. METHODS: Male Dahl salt-sensitive rats were fed low NaCl salt (3% in drinking water) for the control (NS) group or 8% (HS) to induce prehypertension. Each batch was divided into two group and treated by bilateral PVN microinjection with either artificial cerebrospinal fluid or puerarin through a micro-osmotic pump for 6 weeks. The mean arterial pressure (MAP) was recorded, and samples were collected and analyzed. RESULTS: We concluded that puerarin significantly prevented the elevation of blood pressure and effectively alleviated the increase in heart rate caused by high salt. Norepinephrine (NE) in the plasma of salt-induced prehypertensive rats also decreased upon puerarin chronic infusion. Additionally, analysis of the PVN sample revealed that puerarin pretreatment decreased the positive cells and gene level of TLR4 (Toll-like receptor 4), NLRP3, Caspase-1 p10, NOX2, MyD88, NOX4, and proinflammatory cytokines in the PVN. Puerarin pretreatment also decreased NF-κBp65 activity, inhibited oxidative stress, and alleviated inflammatory responses in the PVN. CONCLUSION: We conclude that puerarin alleviated blood pressure via inhibition of the ROS/TLR4/NLRP3 inflammasome signaling pathway in the PVN, suggesting the therapeutic potential of puerarin in the prevention of hypertension.

Development and application of a population pharmacokinetic model repository for caffeine dose tailoring in preterm infants.

BACKGROUND: Considerable interindividual variability for the pharmacokinetics of caffeine in preterm infants has been demonstrated, emphasizing the importance of personalized dosing. This study aimed to develop and apply a repository of currently published population pharmacokinetic (PopPK) models of caffeine in preterm infants to facilitate model-informed precision dosing (MIPD). RESEARCH DESIGN AND METHODS: Literature search was conducted using PubMed, Embase, Scopus, and Web of Science databases. Relevant publications were screened, and their quality was assessed. PopPK models were reestablished to develop the model repository. Covariate effects were evaluated and the concentration-time profiles were simulated. An online simulation and calculation tool was developed as an instance. RESULTS: Twelve PopPK models were finally included in the repository. Preterm infants' age and body size, especially the postnatal age and current weight, were identified as the most clinically critical covariates. Simulated blood concentration-time profiles across these models were comparable. Caffeine citrate-dose regimen should be adjusted according to the age and body size of preterm infants. The developed online tool can be used to facilitate clinical decision-making. CONCLUSIONS: The first developed repository of PopPK models for caffeine in preterm infants has a wide range of potential applications in the MIPD of caffeine.

Clinical follow-up investigation on thickness changes in the peripapillary retinal nerve fibre layer of patients with Leber hereditary optic neuropathy.

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Etiologies of Persistent Aminotransferase Elevations in Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogs.

Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.

Amorphous/polycrystalline NiMn selenide for high-performance supercapacitors.

Transition-metal selenides have been extensively studied as promising electrode materials for supercapacitors. Engineering amorphous/crystalline heterostructures is an effective strategy to improve rich active sites for accelerating redox reaction kinetics but still lacks exploration. In this study, an amorphous/crystalline heterostructure was designed and constructed by selenizing the self-sacrificial template NiMnS to generate amorphous Mn/polycrystalline Ni0.85Se-NiSe2 heterophase via the phase transformation from metal sulfide into metal selenide. The synergy of the complementary multi-components and amorphous/polycrystalline heterophase could enrich electron/ion-transport channels and expose abundant active sites, which accelerated electron/ion transfer and Faradaic reaction kinetics during charging/discharging. As expected, the optimal NiMnSe exhibited a high specific charge (1389.1 C g-1 at 1 A g-1), a good rate capability, and an excellent lifespan (88.9% retention). Moreover, the fabricated NiMnSe//activated carbon device achieved a long cycle life and energy density of 48.0 W h kg-1 at 800 W kg-1, shedding light on the potential for use in practical applications, such as electrochemical energy-storage devices.

Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.

Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.