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Abstract Background This is a retrospective cohort study from a single center of Chest Medical District of Nanjing Brain Hospital Affiliated to Nanjing Medical University, Jiangsu Province, China. It was aim to evaluate the diagnostic value of radial endobronchial ultrasound (R-EBUS) combination with rapid on-site evaluation (ROSE) guided transbronchial lung biopsy (TBLB) for peripheral pulmonary lesions in patients with emphysema. Methods All 170 patients who underwent PPLs with emphysema received an R-EBUS examination with or without the ROSE procedure, and the diagnostic yield, safety, and possible factors influencing diagnosis were analyzed between the two groups by the SPSS 25.0 software. Results The pooled and benign diagnostic yields were not different in the two groups (P = 0.224, 0.924), but the diagnostic yield of malignant PPLs was significantly higher in the group with ROSE than the group without ROSE (P = 0.042). The sensitivity of ROSE was 79.10%, the specificity, 91.67%, the positive predictive value, 98.15%, and the negative predictive value, 84.62%. The diagnostic accuracy, was 95.52%. In the group of R-EBUS + ROSE, the procedural time and the number of times of biopsy or brushing were both significantly reduced (all P

Abstract Essential oils (EOs) are complex and susceptible to environmental conditions, they have a wide range of biological activities and are often used to differentiate between similar species. In this study, gas chromatography-mass spectrometry (GC–MS) coupled with chemometric analysis was applied to systematically analyse and evaluate EOs constituents and antioxidant activity of six Chinese Cupressaceae taxa (Platycladus orientalis Franco, P. orientalis Franco ‘Sieboldii’, P. orientalis Franco ‘Aurea’, Juniperus chinensis Roxb., J. chinensis Roxb. ‘Kaizuca’, and J. sabina L.) under identical conditions. The antioxidant activity of the EOs was evaluated using 2,2 -diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing power (FRAP), and the total phenolic content (TPC) of the EOs was determined by Folin–Ciocalteau reagent. In total, seventy individual constituents were identified with the main components being α-pinene, sabinene, d-limonene, bornyl acetate, δ-3-carene and β-myrcene. Principal component analysis (PCA) and hierarchal cluster analysis (HCA) successfully discriminated the six taxa into three chemotypes and the unique chemotype revealed that J. chinensis ‘Kaizuca’ may be a species rather than a cultivar of J. chinensis. The results of OPLS-DA analysis showed that the three compounds screened, namely, α-pinene, sabinene, and δ-3-carene, can completely distinguish Platycladus spp. from Juniperus spp. The DPPH assay results ranged from 576.14 (J. chinensis ‘Kaizuca’) to 1146.12 (J. sabina) μmol eq Trolox/mL EO, while the ABTS values ranged from 1579.62 (P. orientalis ‘Aurea’) to 5071.82 (J. sabina) μmol eq Trolox/mL. In the FRAP assay, the values ranged from 1086.50 (J. chinensis ‘Kaizuca’) to 1191.18 (J. sabina) μmol eq Trolox/ml and the TPC of the EOs studied ranged from 15.17 (J. chinensis ‘Kaizuca’) to 39.37 (J. sabina) mg GAE/mL EO. The results consistently showed that J. sabina possessed the strongest antioxidant activity and can be preferentially used as a rich source of potentially natural antioxidants.

Background/Aims Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Abstract Background Childhood maltreatment stands as a salient risk factor in the etiology of juvenile delinquency, with a profound impact on the behavioral trajectories of young offenders. However, there is limited research on latent profile analysis to explore distinctive patterns of childhood maltreatment in Chinese juvenile offenders. Consequently, there is a lack of understanding regarding the associations between maltreatment profiles and relevant variables in this context. The present study aimed to explore meaningful subgroups of childhood maltreatment in juvenile offenders, and we further examined the associations between subgroups and multiple outcomes especially psychopathy. Methods The data was obtained from a sample of Chinese juvenile offenders (N = 625, M age = 17.22, SD = 1.23). This study employed a latent profile analysis (LPA) based on factor scores of the Childhood Trauma Questionnaire-Short Form to identify the subgroups and examined the differences across subgroups using outcomes variables including psychopathy, callous-unemotional traits, aggression and anxiety. This study includes three self-report measures to evaluate psychopathy, with due regard for the nuanced considerations on the factor structure inherent in the conceptualization of psychopathy. Results Two subgroups were identified, including the non-maltreatment subgroup (80.2%) and the maltreatment subgroup (19.8%). Maltreatment subgroup was characterized by a greater level of all types of maltreatment with particularly higher of emotion neglect. Besides, we found that maltreatment subgroup showed a significantly higher level of psychopathy across multiple self-report measures, and greater callous-unemotional traits, lack of empathy, aggression and anxiety. We found two subgroups of child maltreatment in Chinese juvenile offenders. Conclusions These findings may provide a further understanding of childhood maltreatment and the clinical intervention on psychopathy in the early period.

BackgroundCervical cancer, primarily driven by high-risk human papillomavirus (HR-HPV) infection, ranks as the second most common cancer globally. Understanding combined infections’ role, including Cervical fungi, is crucial in cervical carcinogenesis. This study aims to explore the potential correlation between HR-HPV, cervical fungi, and cervical cancer, while adjusting for various factors.MethodsThe study population comprised patients undergoing colposcopy and conization due to abnormal cervical screening results. Clinical data including age, gravidity, HPV (human papillomavirus) genotypes, cervical pathology, and p16/Ki67 expression were extracted. Cervical TCT (ThinPrep Pap Test) and HPV testing are utilized for screening cervical lesions, with fungal presence suggested by TCT results. 5,528 participants were included in this study. Statistical analyses investigated associations between HPV/fungi co-infection and cervical lesions, employing multinomial logistic regression and interaction analysis.ResultsCo-infection with fungi and HPV may decrease the risk of cervical lesions compared to HPV infection alone. In the co-infection group, compared with HPV infection alone, the risk of low-grade squamous intraepithelial lesions (LSIL) was reduced by 27% (OR = 0.73, 95% CI: 0.59–0.90), the risk of high-grade squamous intraepithelial lesions (HSIL) was reduced by 35% (OR = 0.65, 95% CI: 0.51–0.82), and the risk of cervical cancer was reduced by 43% (OR = 0.57, 95% CI: 0.35–0.92). The interaction analysis revealed a negative interaction between fungal and HPV infections in the development of cervical cancer (RERI = −6.25, AP = −0.79, SI = 0.52), HSIL (RERI = −19.15, AP = −0.37, SI = 0.72) and LSIL (RERI = −1.87, AP = −0.33, SI = 0.71), suggesting a sub-additive effect, where the combined effect of the two infections was less than the sum of their individual effects. This indicates that fungal infection may attenuate the promoting effect of HPV on cervical lesions. In exploring the potential mechanism, we found that the co-infection group had significantly lower p16 positivity (54.6%) compared to the HPV-only group (60.2%) (p = 0.004), while there was no statistically significant difference in Ki67 positivity.ConclusionThis study unveils the intricate relationship between cervical fungi and HPV in cervical lesions. Co-infection with fungi and HPV against cervical lesions compared to HPV infection alone, indicating a novel clinical interaction. Lower p16 positivity in co-infection hints at a protective mechanism, urging further exploration.

Background & Aims: Currently, there is limited knowledge on the clinical profile of drug-induced liver injury (DILI) in Chinese children. We aimed to assess the clinical characteristics, suspected drugs, and outcomes associated with pediatric DILI in China. Methods: This nationwide, multicenter, retrospective study, conducted between 2012 and 2014, analyzed 25,927 cases of suspected DILI at 308 medical centers using the inpatient medical register system. Utilizing the Roussel Uclaf causality assessment method score, only patients with scores ≥6 or diagnosed with DILI by three experts after scoring

The LouShao Basin in Hunan Province is covered with two sets of black rock series containing various potential toxic heavy metal elements. The rock series are rich in various potential toxic heavy metal elements, and the weathered black shale is the main formation of local farmland soil, making it a typical area with high geological background in China. The purpose of this study is to assess the regional ecological and health risks by studying the correlation between the content of heavy metal elements enriched in rhizosphere soil, non-rhizosphere soil, and crops, and the concentration of heavy metal elements in the main source, black shale rocks. The results show that the elements in the black shale far exceed the world average of rock, severely affecting soil element concentrations. Se element is the most severely polluted in rhizosphere soil, exceeding the background value by 7 times. The concentration of heavy metals between rock-non-rhizosphere soil-rhizosphere soil-crops decreases linearly. The distribution of pollution has strong spatial autocorrelation, and the high geological background is the main reason. Pollution index results show significant pollution of Se, Cr, Hg, and Cd in crops, with the pollution of heavy metal element Cr in corn being extremely serious with Igeo = 6.71. The ecological risk order is Se > Cd > Cr > As > Pb > Hg. Humans mainly contact elements through skin contact and food chain intake. The HI value of heavy metal element Cd is greater than 1, indicating a high carcinogenic risk. Human exposure to Cd through skin contact and food chain intake may lead to related diseases such as kidney stones, and pose greater harm to children.

BackgroundThe gut microbiota and plasma metabolites play important roles in the progression of drug-induced liver injury (DILI). We investigated the causal associations between the gut microbiota, plasma metabolome, and DILI.MethodsThe summary data for gut microbiota (n = 18,340), plasma metabolome (n = 8,299), and DILI (n = 366,838) were obtained from the large genome-wide association studies. A two-sample Mendelian randomization was performed to explore the associations between the gut microbiota, plasma metabolome, and DILI. Additionally, a two-step Mendelian randomization was performed to explore the potential metabolites.ResultsFive taxa were causally associated with DILI, including Oscillospira [odds ratio (OR) = 2.257, 95% confidence interval (CI) = 1.110–4.590], Blautia (OR = 2.311, 95% CI = 1.010–5.288), Roseburia (OR = 2.869, 95% CI = 1.429–5.761), Fusicatenibacter (OR = 1.995, 95% CI = 1.024–3.890), and Prevotella 7 (OR = 1.549, 95% CI = 1.065–2.253). Moreover, 53 metabolites were causally associated with DILI. After mediation analysis, four taxa were found to affect DILI through five mediation metabolites. N6-carbamoylthreonyladenosine mediated the effect of Blautia on DILI. Acetylcarnitine mediated the effect of Fusicatenibacter on DILI. In addition, 4-cholesten-3-one mediated the effect of Prevotella 7 on DILI. Furthermore, 5,6-dihydrothymine levels and the salicylate-to-citrate ratio mediated the effect of Oscillospira on DILI.ConclusionWe found that the gut microbiota could affect DILI through plasma metabolites, which could serve as potential biomarkers for risk stratification and elucidate underlying mechanisms for further investigation of DILI.

BackgroundReaching movements are crucial for daily living and rehabilitation, for which Fitts' Law describes a speed-accuracy trade-off that movement time increases with task difficulty. This study aims to investigate whether cortical activation in motor-related areas is directly linked to task difficulty as defined by Fitts' Law. Understanding this relationship provides a physiological basis for parameter selection in therapeutic exercises.MethodsSixteen healthy subjects performed 2D reaching movements using a rehabilitation robot, with their cortical responses detected using functional near-infrared spectroscopy (fNIRS). Task difficulty was manipulated by varying target size and distance, resulting in 3 levels of index-of-difficulty (ID). Kinematic signals were recorded alongside cortical activity to assess the relationship among movement time, task difficulty, and cortical activation.ResultsOur results showed that movement time increased with ID by 0.2974s/bit across all subjects (conditional r2 = 0.6434, p < 0.0001), and all subjects showed individual trends conforming Fitts' Law (all p < 0.001). Neither activation in BA4 nor in BA6 showed a significant correlation with ID (p > 0.05), while both the target size and distance, as well as the interaction between them, showed a significant relationship with BA4 or BA6 activation (all p < 0.05).ConclusionThis study found that although kinematic measures supported Fitts' Law, cortical activity in motor-related areas during reaching movements did not correlate directly with task difficulty as defined by Fitts' Law. Additional factors such as muscle activation may call for different cortical control even when difficulty was identical.

This study reports an investigative study of individual differences in personality, motivation, challenges, learning styles and strategies, needs and 55 non-English-majors’ engagement in business English language classrooms in a Chinese university, using two-stage surveys. The study finds positive affective factors in personality and motivation, though participants experienced challenges in learning business English vocabulary and improving English skills. Participants used different learning strategies and styles, and required varied helpful strategies for enhancing business English teaching and learning. Participants had high levels of cognitive engagement, behavioral engagement, emotional engagement, enjoyment, focus, and task familiarity in business English learning. Though participants still encountered problems, they reported learning gains in business English vocabulary expansion, improvement in business writing, workplace communication, business knowledge and culture, business reading, problem solving, listening, interest in English and critical thinking skills. This study is providing empirical evidence of individual differences with China’s non-English-major learners in business English learning and how the individual differences relate with engagement and learning outcomes. The study also implies for practice that business English teachers should adapt their teaching approach and strategies to accommodate to individual differences.

Abstract Physiological regulation of transgene expression is a major challenge in gene therapy. Onasemnogene abeparvovec (Zolgensma®) is an approved adeno-associated virus (AAV) vector gene therapy for infants with spinal muscular atrophy (SMA), however, adverse events have been observed in both animals and patients following treatment. The construct contains a native human survival motor neuron 1 (hSMN1) transgene driven by a strong, cytomegalovirus enhancer/chicken β-actin (CMVen/CB) promoter providing high, ubiquitous tissue expression of SMN. We developed a second-generation AAV9 gene therapy expressing a codon-optimized hSMN1 transgene driven by a promoter derived from the native hSMN1 gene. This vector restored SMN expression close to physiological levels in the central nervous system and major systemic organs of a severe SMA mouse model. In a head-to-head comparison between the second-generation vector and a benchmark vector, identical in design to onasemnogene abeparvovec, the 2nd-generation vector showed better safety and improved efficacy in SMA mouse model.

Abstract Background People with chronic hepatitis B (CHB) commonly experience social and self-stigma. This study sought to understand the impacts of CHB-related stigma and a functional cure on stigma. Methods Adults with CHB with a wide range of age and education were recruited from 5 countries and participated in 90-minute qualitative, semi-structured interviews to explore concepts related to CHB-associated stigma and its impact. Participants answered open-ended concept-elicitation questions regarding their experience of social and self-stigma, and the potential impact of reduced CHB-related stigma. Results Sixty-three participants aged 25 to 71 years (15 from the United States and 12 each from China, Germany, Italy, and Japan) reported emotional, lifestyle, and social impacts of living with CHB, including prejudice, marginalization, and negative relationship and work experiences. Self-stigma led to low self-esteem, concealment of CHB status, and social withdrawal. Most participants stated a functional cure for hepatitis B would reduce self-stigma. Conclusions CHB-related social and self-stigma are widely prevalent and affect many aspects of life. A functional cure for hepatitis B may reduce social and self-stigma and substantially improve the health-related quality of life of people with CHB. Incorporating stigma into guidelines along with infectivity considerations may broaden the patient groups who should receive treatment.

Abstract Fibre‐reinforced polymer (FRP)/rigid polyurethane foam (RPUF) interface is susceptible to moisture intrusion in addition to natural ageing during operation. This study investigated the influence of moisture intrusion on the FRP/RPUF interface under natural ageing using experiments and molecular dynamics (MD) simulations. Water absorption, shear strength, and leakage current tests were used to clarify the changes in the interface performance. The degradation mechanism of moisture intrusion at the interface under natural ageing was revealed by MD simulation and micro‐characterisation. The results show that the natural ageing of interfacial materials will slightly reduce the quality of the interface but will reduce the water resistance of the material and promote the process of water intrusion into the interface. In addition, water mainly invades the interface through RPUF. After water penetration, the interfacial bonding strength and insulation performance significantly decreased. Plasticisation and hydrolysis of interfacial materials are the main reasons for decreased interfacial adhesion. Hydrolysis can cause irreversible damage to the interface, increasing interface defects and water absorption. The vicious cycle of material hydrolysis is the ultimate cause of interfacial debonding. The polar molecules produced by this process and the water absorbed by the interface caused the degradation of the interface insulation performance.

In certain neurological disorders such as stroke, the impairment of upper limb function significantly impacts daily life quality and necessitates enhanced neurological control. This poses a formidable challenge in the realm of rehabilitation due to its intricate nature. Moreover, the plasticity of muscle synergy proves advantageous in assessing the enhancement of motor function among stroke patients pre and post rehabilitation training intervention, owing to the modular control strategy of central nervous system. It also facilitates the investigation of long-term alterations in remodeling of muscle functional performance among patients undergoing clinical rehabilitation, aiming to establish correlations between changes in muscle synergies and stroke characteristics such as type, stage, and sites. In this study, a three-week rehabilitation monitoring experiment was conducted to assess the motor function of stroke patients at different stages of rehabilitation based on muscle synergy performance. Additionally, we aimed to investigate the correlation between clinical scale scores, rehabilitation stages, and synergy performance in order to provide a more comprehensive understanding of stroke patient recovery. The results of 7 healthy controls and 16 stroke patients showed that high-functioning patients were superior to low-functioning patients in terms of motor function plasticity towards healthy individuals. Moreover, there was a high positive correlation between muscle synergies and clinical scale scores in high-functioning patients, and the significance gradually emerged with treatment, highlighting the potential of muscle synergy plasticity as a valuable tool for monitoring rehabilitation progress. The potential of this study was also demonstrated for elucidating the physiological mechanisms underlying motor function reconstruction within the central nervous system, which is expected to promote the further application of muscle synergy in clinical assessment.

Abstract Background To investigate the trends in health-related quality of life (HRQoL) among hepatitis C virus (HCV) patients and to assess the longitudinal impact of antiviral therapy on their well-being. Methods In this prospective multicenter observational study in adults with HCV infection, sociodemographic, clinical characteristics and EQ-5D questionnaires were collected. Generalized estimating equation (GEE) models were used to assess the associations between these variables and changes in HRQoL over time. Results 456 patients were included, with a median age of 46.5 (36.5–57.0) years, of which 262 (57.5%) were males and 44 (9.6%) had cirrhosis. 335 patients (73.5%) receiving antiviral therapy and 61.8% achieved sustained virologic response (SVR). The baseline EQ-5D utility and EQ-VAS were 0.916 ± 0.208 and 80.6 ± 13.0. In multivariable analysis of GEE estimation, achieving SVR24 was positively associated with EQ-5D utility (p = 0.000) and EQ-VAS (p = 0.000) over time. Age and income were shown to be significant predictors of EQ-5D utility, while gender, age and genotype were associated with EQ-VAS over time. Conclusions SVR improved long-term HRQoL in HCV patients in the first few years following viral clearance. Certain sociodemographic factors, such as gender, age, income as well as genotype, significantly influenced long-term changes in patients’ quality of life. Trial registration NCT01594554. Registration date: 09/05/2012.

Background: Atopic dermatitis is a common chronic inflammatory skin disease characterized by relapsing eczema and intense itch. DGT is a novel synthetic heterocyclic diterpenoid derived from plants. Its therapeutic potential and mechanism(s) of action are poorly understood. Objectives: We investigated the potent therapeutic effect of DGT on atopic dermatitis, exploring the underlying mechanisms and determining whether DGT is a safe and well-tolerated topical treatment. Methods: We observed anti-inflammatory effects of DGT on tumor necrosis factor-α/interferon-γ–treated human keratinocytes, and anti-allergic effects on immunoglobulin E–sensitized bone marrow–derived mast cells. In vivo, DGT was topically applied to two experimental mouse models of atopic dermatitis: oxazolone-induced sensitization and topically applied calcipotriol. Then the therapeutic effects of DGT were evaluated physiologically and morphologically. Moreover, we performed nonclinical toxicology and safety pharmacology research, including general toxicity, pharmacokinetics, and safety pharmacology on the cardiovascular, respiratory, and central nervous systems. Results: In keratinocytes, DGT reduced the expression of inflammatory factors, promoting the expression of barrier functional proteins and tight junctions and maintaining the steady state of barrier function. DGT also inhibited the activation and degranulation of mast cells induced by immunoglobulin E. Moreover, we found that interleukin-4 receptor-α was the possible target of DGT. Meanwhile, DGT had therapeutic effects on oxazolone/calcipotriol-treated mice. Notably, our pharmacology results demonstrated that DGT was safe and nontoxic in our studies. Conclusion: DGT’s potent anti-inflammatory effects and good safety profile suggest that it is a potential candidate for the treatment of atopic dermatitis.

BackgroundThere may be an interaction between viral hepatitis and psychiatric disorders during disease progression. Herein, we conducted Mendelian randomization (MR) to explore the causal associations and mediators between viral hepatitis and psychiatric disorders.MethodsGenome-wide association studies summary data for viral hepatitis [including chronic hepatitis B (CHB) and chronic hepatitis C (CHC)] and psychiatric disorders (including depression, anxiety, schizophrenia, obsessive-compulsive disorder, bipolar disorder, and post-traumatic stress disorder) were obtained. Two-sample MR was performed to assess the causal associations between viral hepatitis and psychiatric disorders. Further, a mediation analysis was conducted to evaluate the potential mediators. Inverse-variance weighted, MR-Egger, and weighted median were used as the main methods, while a sensitivity analysis was performed to evaluate pleiotropy and heterogeneity.ResultsThere was no causal effect of CHB/CHC on psychiatric disorders, as well as psychiatric disorders on CHB. However, schizophrenia presented a causal effect on increased CHC risk [odds ratio (OR)=1.378, 95%CI: 1.012–1.876]. Further, a mediation analysis identified coffee consumption and body mass index as mediators in the effect of schizophrenia on CHC, mediating 3.75% (95%CI: 0.76%–7.04%) and 0.94% (95%CI: 0.00%–1.70%) proportion, respectively.ConclusionWe revealed that schizophrenia patients faced a high risk of CHC, and insufficient coffee consumption and underweight could mediate the causal effect of schizophrenia on CHC. The prevention of hepatitis C might be a beneficial strategy for patients with schizophrenia. The right amount of nutrition supplements and coffee consumption might be part of a beneficial lifestyle in preventing the high CHC risk in patients with schizophrenia.

Enrichment of toxicological elements in soils of high geologic background has a significant effect on toxicity. The aim of this study was to assess the health risks associated with the transfer of toxicological elements in the food chain in a typical high geologic background. We systematically collected data on rocks, soils and food crops belonging to a typical black rock system geological body and at the same time belonging to the main grain-producing areas in Hunan Province, and analyzed the exposure and health threat of toxicological elements Cr, Cd, Pb, Hg, As and Se in cucumber, rape, soybean, peanut and ginger. Based on the JISEVM method to establish the spatial contamination constitutive relationship between rock-soil-food, we deduced the conclusions from the bioconcentration factor (BCF), integrated crop contamination index (P) and hazard index (HI). Our results showed that Cr, Cd, Pb, Hg, and Se were exceeded in agricultural soils, with Hg and Se levels severely exceeding the standard Se was most bioconcentrated in soybean (BCF = 0.5855), followed by Cd (BCF = 0.5603) and Se (BCF = 0.3800) in peanut and Se (BCF = 0.4255) in rape, and the BCFs of all the BCF of crops were less than 1, and the enrichment of these six elements in the food chain did not reach a dangerous level; the overall spatial distribution of radioactive contamination was centered on the black rocky geologic body; and the contamination and absorption levels of foods in the study area were: leafy vegetables (oilseed rape) > legumes (soybeans and peanuts) > stem vegetables (ginger) > fruit vegetables (cucumber). The intake of Cd and Se through consumption of oilseed rape was the most important source of health risk among foods in the study area. This study, since it can fill the gap in risk assessment due to endogenous factors in a high geologic background, can also guide studies in other specialized contexts or in a multi-media background.

Abstract Objective To investigate the effect of therapeutic hypercapnia on the expression and function of gamma delta T (γδ T) cells during ischemia‐reperfusion injury (IRI) after lung transplantation. Methods We randomly divided male Wistar rats into three groups (n = 6 in each group), the control group (group N), the IRI group (group I), and the therapeutic hypercapnia group (group H). We then assessed pulmonary edema, neutrophil infiltration, wet‐to‐dry (W/D) weight ratio, and microscopic histopathology and separately measured the levels of γδT cell surface antigen (TCR) and Interleukin‐17 (IL‐17) using flow cytometry and enzyme‐linked immunosorbent assays (ELISAs). Results The infiltration of neutrophils and the expression of TCR and IL‐17 were significantly increased in the I group compared to the control, and the biopsy edema in group I was more severe. Arterial partial pressure of oxygen (PaO2) was decreased after reperfusion in group I compared with the control group. W/D weight ratio, neutrophil infiltration, and the expression of TCR and IL‐17 decreased drastically in the H group compared to the I group. Conclusion Our findings suggest that γδ T lymphocytes were directly involved in lung injury. In addition, therapeutic hypercapnia effectively reduced the expression of γδ T cells and IL‐17, and this has the potential to become a treatment strategy for IRI and an intervention to improve lung function.

Abstract Engineering experience shows that for transformers with long service life and serious moisture exposure, the inter‐turn paper insulation inside the winding will precipitate bubbles under the condition of electric field and conductor heating, which will endanger the equipment insulation. In order to explore the influence factors of bubbles formation in the moist insulating paper of transformers, based on the existing research on the influence of moisture content and gas dissolution in transformer oil, this study further considers the influence of air pressure (AP) and electric field and establishes an experimental platform to change the air pressure and electric field, thereby studying the formation characteristics of bubbles in oil‐paper insulation. The results show that air pressure and electric field can affect the initial temperature, volume, and shape of bubble formation. From 0 to −0.05 MPa for air pressure, the initial temperature of bubble generation decreased by 41°C, its maximum two‐dimensional projected area increased by 418.4% with more severe distortion, and the breakdown voltage decreased. When the AC voltage applied on the needle plate electrode increased from 0 to 10 kV, the initial temperature of bubble formation increased by 29°C, and the maximum two‐dimensional projection area increased by 336.6%.

Abstract Liver fibrosis, a common characteristic of chronic liver diseases, is a major challenge to global health. The progression of liver fibrosis is responsible for liver‐related morbidity and mortality. Nevertheless, the pathogenesis of liver fibrosis remains unclear and an effective therapy has not yet been developed. Activation of hepatic stellate cells (HSCs) is well‐known to act as a central driver of liver fibrosis, while resident and infiltrating inflammatory cells further modulate HSC activation via extracellular signals. MicroRNAs (miRNAs) are small, noncoding RNAs that are critical regulators for liver physiological and pathological processes by negatively regulating target gene expression and facilitating intercellular communication. Here, we review the involvement of miRNAs in the development and progression of liver fibrosis in various hepatic cells, including HSCs, hepatocytes, and inflammatory cells, and discuss the potential of miRNAs as biomarkers and therapeutic targets for liver fibrosis.

MnSOD is a ubiquitous metalloenzyme that constitutes the first line of antioxidant defense against oxidative stress. In this study, full length sequence of MnSOD was identified from hybrid crucian carp (WR, Carassius cuvieri ♀ × Carassius auratus red var ♂). Tissue-specific analysis revealed that the highest expression of WR-MnSOD was detected in kidney. Aeromonas hydrophila challenge could dramatically enhance WR-MnSOD mRNA expression in tissues. In vivo administration of purified WR-MnSOD peptide could maintain gut mucosal barrier function, rescue redox balance as well as decrease apoptotic cell death in midgut upon bacterial infection, suggesting that WR-MnSOD is playing a crucial role in gut mucosal barrier function and could be used as feed additive to improve gut immunity in fish.

Objective: This study explored the potential association between the Prognostic Nutritional Index (PNI) and the incidence of non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF) in the adult population of the United States. Methods: Information on 6409 participants ≥18 years old was downloaded from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Multivariate analysis was combined with demographic factors to assess the relationships between PNI, NAFLD, and AF. A restricted cubic spline (RCS) was used to characterise the nonlinear association between the PNI and NAFLD and AF. Results: Patients without NAFLD had substantially lower mean values for parameters such as age, lymphocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), total cholesterol, triglycerides, HbA1c, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) than patients with NAFLD. Interestingly, non-NAFLD patients showed a pronounced increase in serum albumin levels compared to their NAFLD counterparts. In the subset without AF, there were discernibly lower measures of NLR, age, AST, ALT, γ-glutamyl transferase, triglycerides, neutrophil count, and body mass index (BMI) than in patients with AF. It was evident that those without AF had markedly elevated mean albumin and PNI levels in comparison to AF-affected individuals. In the comprehensive multivariable framework, a direct correlation was observed between PNI and NAFLD (adjusted odds ratio[aOR] = 1.07, 95% confidence interval [CI]: 1.05–1.09; p

Summary: Background: With increasingly prevalent coexistence of chronic hepatitis B (CHB) and hepatic steatosis (HS), simple, non-invasive diagnostic methods to accurately assess the severity of hepatic inflammation are needed. We aimed to build a machine learning (ML) based model to detect hepatic inflammation in patients with CHB and concurrent HS. Methods: We conducted a multicenter, retrospective cohort study in China. Treatment-naive CHB patients with biopsy-proven HS between April 2004 and September 2022 were included. The optimal features for model development were selected by SHapley Additive explanations, and an ML algorithm with the best accuracy to diagnose moderate to severe hepatic inflammation (Scheuer's system ≥ G3) was determined and assessed by decision curve analysis (DCA) and calibration curve. This study is registered with ClinicalTrials.gov (NCT05766449). Findings: From a pool of 1,787 treatment-naive patients with CHB and HS across eleven hospitals, 689 patients from nine of these hospitals were chosen for the development of the diagnostic model. The remaining two hospitals contributed to two independent external validation cohorts, comprising 509 patients in validation cohort 1 and 589 in validation cohort 2. Eleven features regarding inflammation, hepatic and metabolic functions were identified. The gradient boosting classifier (GBC) model showed the best performance in predicting moderate to severe hepatic inflammation, with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.83–0.88) in the training cohort, and 0.89 (95% CI 0.86–0.92), 0.76 (95% CI 0.73–0.80) in the first and second external validation cohorts, respectively. A publicly accessible web tool was generated for the model. Interpretation: Using simple parameters, the GBC model predicted hepatic inflammation in CHB patients with concurrent HS. It holds promise for guiding clinical management and improving patient outcomes. Funding: This research was supported by the National Natural Science Foundation of China (No. 82170609, 81970545), Natural Science Foundation of Shandong Province (Major Project) (No. ZR2020KH006), Natural Science Foundation of Jiangsu Province (No.BK20231118), Tianjin Key Medical Discipline (Specialty), Construction Project, TJYXZDXK-059B, Tianjin Health Science and Technology Project key discipline special, TJWJ2022XK034, and Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission (2021022).

This study reports on an investigate study about using simulation in business English teaching with 66 English-major advanced learners, using two-stage surveys. This study addresses the three research questions focusing on the needs and challenges, effectiveness and learning outcomes and suggestions for improvement of simulation in business English teaching. The study found that participants most favored employment related simulation and workplace scenarios. They preferred both Chinese and global corporate simulation cases, as well as unique industrial and familiar cases. The lack of language skills, knowledge, thinking skills, practice skills, and mentality could be the challenges for simulation. The majority of the participants agreed that simulation activities were effective and had positive impact. Through simulation, participants could acquire writing skills, corporate and business knowledge, and business vocabulary knowledge. Participants were concerned about the simulation process and the roles to play. Lack of adequate language, knowledge, experience, and social skills, inappropriate grouping and timing could be unproductive factors for simulation. On the other hand, more interactions, presentation, expanded language and knowledge, and linking with practice could be facilitating factors for simulation. For improvement, participants suggested adding more case content and context, having longer preparation time and better grouping, as well as clearer simulation instructions. This study provides empirical evidences for refining the simulation approach in business English courses from China’s English majors’ perspectives. The study has important implications for business English simulation teaching design and implementations in both Chinese and international contexts.

Abstract Organophilic groups of coupling agents can be the key factor for the electrical performance of Boron Nitride (BN)/meta‐aramid composite paper. In this article, four types of triethoxy‐silane coupling agents with different organophilic groups, including mercapto‐propyl (MP), glycidylether‐propyl (GP), amino‐propyl (AP) and trideca‐fluoro‐octyl (TFO) were studied. The structural and electrical properties of modified papers were compared, and the molecular simulation was conducted to reveal the interface interaction of modified BN and aramid. The results show that AP, GP and MP follow the same mechanism, improving the electrical performance by modifying the interface stability and paper structure, and the ranks of improving effects are AP, MP and GP. While, TFO mainly relies on the fluorine components to implement the electrical reinforcement, which compensates for the shortcoming in the paper structure. By choosing TFO and filler content of 15 wt%, the optimal breakdown strength of the paper can be increased to 28.17 kV/mm, 1.8 times that of the paper doped with the hydroxylated BN.

Abstract Salt-overly-sensitive 1 (SOS1) is a unique electroneutral Na+/H+ antiporter at the plasma membrane of higher plants and plays a central role in resisting salt stress. SOS1 is kept in a resting state with basal activity and activated upon phosphorylation. Here, we report the structures of SOS1. SOS1 forms a homodimer, with each monomer composed of transmembrane and intracellular domains. We find that SOS1 is locked in an occluded state by shifting of the lateral-gate TM5b toward the dimerization domain, thus shielding the Na+/H+ binding site. We speculate that the dimerization of the intracellular domain is crucial to stabilize the transporter in this specific conformation. Moreover, two discrete fragments and a residue W1013 are important to prevent the transition of SOS1 to an alternative conformational state, as validated by functional complementation assays. Our study enriches understanding of the alternate access model of eukaryotic Na+/H+ exchangers.

Online platforms allow individuals to connect with others, share experiences, and find communities with similar interests, providing a sense of belonging and reducing feelings of isolation. Numerous previous studies examined the content of online health communities to gain insights into the sentiments surrounding mental health conditions. However, there is a noticeable gap in the research landscape, as no study has specifically concentrated on conducting an in-depth analysis or providing a comprehensive visualization of Bipolar disorder. Therefore, this study aimed to address this gap by examining the Bipolar subreddit online community, where we collected 1,460,447 posts as plain text documents for analysis. By employing LDA topic modeling and sentiment analysis, we found that the Bipolar disorder online community on Reddit discussed various aspects of the condition, including symptoms, mood swings, diagnosis, and medication. Users shared personal experiences, challenges, and coping strategies, seeking support and connection. Discussions related to therapy and medication were prevalent, emphasizing the importance of finding suitable therapists and managing medication side effects. The online community serves as a platform for seeking help, advice, and information, highlighting the role of social support in managing bipolar disorder. This study enhances our understanding of individuals living with bipolar disorder and provides valuable insights and feedback for researchers developing mental health interventions.

Potential toxic heavy metal elements in the topsoil of villages in antimony mining areas pose a serious threat to residents' health, and scientific analysis of potential toxic heavy metal element contamination in the topsoil of villages in antimony mining areas and environmental safety is especially important for residents' health and the high quality of sustainable development in the mining areas. In this study, we chose Qilijiang Village in the Lengshuijiang Tin Mine in Hunan Province and used field sampling and indoor experiments to investigate the toxic heavy metal pollution and environmental safety of the topsoil using key technologies such as geomatics mathematical analysis, analysis of variance (ANOVA), GIS, and environmental risk assessment modeling.The average contents of potential Pb, Cr, As, Cd, and Sb in the topsoil of the residential area exceeded the standard values by 1.12, 1.00, 15.82, 13.37, and 38.87 times, respectively; the degree of contamination risk was As > Sb > Cr > Pb > Cd in the order of As > Sb > Cr > Pb > Cd; and the high-loading elements were As and Sb with a high degree of homology. The results of spatial and principal component analysis revealed that the potential Pb, Cr, As, Cd, and Sb in the surface soil of the residential area were influenced by discrete sources such as mining, processing, and other industrial and mining activities, as well as dust deposition and residents' domestic drainage water (As and Sb); the natural geological backdrop and the metal products industry (Cr); lead-acid batteries, industrial activities, and gasoline additives (Pb); residents of the residential area, green space, and resident gardens; fertilizer application; and pesticide use (Cd). According to the results of the environmental safety analysis, Sb, As, and Cd are in the heavy pollution category, while Cr and Pb are in the low pollution category, and the ecological danger of metals is Cd (401.22) > Sb (388.70) > As (158.16) > Pb (5.58) > Cr (2.00).Cd and Sb have reached a very high degree of ecological risk; As is at a higher risk level; and Pb and Cr are at a lower or no risk level. Except for As and Sb (HI value > 1), the non-carcinogenic risk of village topsoil was insignificant, and Pb, Sb, and As in topsoil exhibited carcinogenic risk, with As exceeding the permissible level, and the carcinogenic risk of As in Qilijiang village was more serious than that of Sb. The study's findings are critical for implementing preventive steps to protect the ecosystem and assure long-term growth in the area.

This study presents an electrophysiological assessment of radial extracorporeal shock wave therapy on patients with carpal tunnel syndrome (CTS). Sixteen CTS subjects received radial extracorporeal shock wave therapy once a week for five consecutive weeks. Outcome performance was assessed using the Boston Carpal Tunnel Questionnaire (BCTQ) and electrodiagnostic measurements including a nerve conduction study of the median nerve and a compound muscle action potential (CMAP) scan of the abductor pollicis brevis muscle. The BCTQ and the sensory conduction test measurements were all statistically improved after the treatment. However, the motor conduction test measurements were not significantly different before and after the treatment. The CMAP scan examination revealed MScanFit motor unit number estimation (MUNE) was significantly higher after the treatment, while no significant change was found in StairFit MUNE and step index. These results confirmed the effectiveness of shock wave therapy for treating CTS symptoms and the associated sensory property changes. The reasons for the inconsistencies from different CMAP scan processing methods are worthwhile targets for further investigation.

Aims: This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies.Methods: A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated.Results: A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07–1.38, p = 0.003) and GTI (HR: 2.72, 95% CI: 2.48–2.98, p < 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92–1.23, p = 0.42), UTI (HR: 0.99, 95% CI: 0.89–1.10, p = 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94–1.04, p = 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04–1.36, p = 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease.Conclusion: SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.

Abstract Background With the variability in emerging data, guidance on the isolation duration for patients with coronavirus disease 2019 (COVID-19) due to the Omicron variant is controversial. This study aimed to determine the predictors of prolonged viral RNA shedding in patients with non-severe COVID-19 and construct a nomogram to predict patients at risk of 14-day PCR conversion failure. Methods Adult patients with non-severe COVID-19 were enrolled from three hospitals of eastern China in Spring 2022. Viral shedding time (VST) was defined as either the day of the first positive test or the day of symptom onset, whichever was earlier, to the date of the first of two consecutively negative PCR tests. Patients from one hospital (Cohort I, n = 2033) were randomly grouped into training and internal validation sets. Predictors of 14-day PCR conversion failure were identified and a nomogram was developed by multivariable logistic regression using the training dataset. Two hospitals (Cohort II, n = 1596) were used as an external validation set to measure the performance of this nomogram. Results Of the 2033 patients from Cohort I, the median VST was 13.0 (interquartile range: 10.0‒16.0) days; 716 (35.2%) lasted > 14 days. In the training set, increased age [per 10 years, odds ratio (OR) = 1.29, 95% confidence interval (CI): 1.15‒1.45, P 14 days, whereas full or boosted vaccination (OR = 0.63, 95% CI: 0.42‒0.95, P = 0.028) and antiviral therapy (OR = 0.56, 95% CI: 0.31‒0.96, P = 0.040) were protective factors. These predictors were used to develop a nomogram to predict VST > 14 days, with an area under the ROC curve (AUC) of 0.73 in the training set (AUC, 0.74 in internal validation set; 0.76 in external validation set). Conclusions Older age, increasing comorbidities, incomplete vaccinations, and lack of antiviral therapy are risk factors for persistent infection with Omicron variant for > 14 days. A nomogram based on these predictors could be used as a prediction tool to guide treatment and isolation strategies. Graphical Abstract

Abstract Background Cellular differentiation is marked by temporally and spatially coordinated gene expression regulated at multiple levels. DNA methylation represents a universal mechanism to control chromatin organization and its accessibility. Cytosine methylation of CpG dinucleotides regulates binding of methylation-sensitive DNA-binding transcription factors within regulatory regions of transcription, including promoters and distal enhancers. Ocular lens differentiation represents an advantageous model system to examine these processes as lens comprises only two cell types, the proliferating lens epithelium and postmitotic lens fiber cells all originating from the epithelium. Results Using whole genome bisulfite sequencing (WGBS) and microdissected lenses, we investigated dynamics of DNA methylation and chromatin changes during mouse lens fiber and epithelium differentiation between embryos (E14.5) and newborns (P0.5). Histone H3.3 variant chromatin landscapes were also generated for both P0.5 lens epithelium and fibers by chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Tissue-specific features of DNA methylation patterns are demonstrated via comparative studies with embryonic stem (ES) cells and neural progenitor cells (NPCs) at Nanog, Pou5f1, Sox2, Pax6 and Six3 loci. Comparisons with ATAC-seq and RNA-seq data demonstrate that reduced methylation is associated with increased expression of fiber cell abundant genes, including crystallins, intermediate filament (Bfsp1 and Bfsp2) and gap junction proteins (Gja3 and Gja8), marked by high levels of histone H3.3 within their transcribed regions. Interestingly, Pax6-binding sites exhibited predominantly DNA hypomethylation in lens chromatin. In vitro binding of Pax6 proteins showed Pax6’s ability to interact with sites containing one or two methylated CpG dinucleotides. Conclusions Our study has generated the first data on methylation changes between two different stages of mammalian lens development and linked these data with chromatin accessibility maps, presence of histone H3.3 and gene expression. Reduced DNA methylation correlates with expression of important genes involved in lens morphogenesis and lens fiber cell differentiation.

Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1β, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.

Epidural electrical stimulation is a new treatment method for spinal cord injury (SCI). Its efficacy and safety have previously been reported. Rehabilitation treatment after epidural electrical stimulation is important to ensure and improve the postoperative efficacy of epidural electrical stimulation in patients with SCI. Considering that electromyography (EMG)-induced rehabilitation treatment can accurately match the muscle contraction of patients with SCI, we designed a study protocol for a prospective, randomized controlled trial. In this trial, on the premise of adjusting the spinal cord electrical stimulator to obtain the maximum EMG signal of the target muscle, patients with SCI receiving epidural electrical stimulation will undergo EMG-induced rehabilitation treatment. Recovery of muscle strength of key muscles, quality of life, safety and therapeutic effects will be monitored. Twenty patients with SCI who are scheduled to undergo epidural electrical stimulation in Shanghai Ruijin Rehabilitation Hospital will be randomly divided into two groups with 10 patients per group. The control group will receive conventional rehabilitation treatment. The EMG-induced rehabilitation group will receive EMG-induced rehabilitation treatment of the target muscles of the upper and lower limbs based on conventional rehabilitation treatment. After rehabilitation treatment, follow up for all patients will occur at 2 weeks and 1, 3 and 6 months. The primary outcome measure of this trial will be evaluation of target muscle recovery using the Manual Muscle Testing grading scale. Secondary outcome measures will include modified Barthel Index scores, integrated EMG values, the visual analogue scale, Spinal Cord Independence Measure scores, and modified Ashworth scale scores. The safety indicator will be the incidence of adverse events. This trial will collect data regarding the therapeutic effects of EMG-induced rehabilitation in patients with SCI receiving epidural electrical stimulation for 6 months after rehabilitation treatment. Findings from this trial will help develop rehabilitation methods in patients with SCI after epidural electrical stimulation. This study protocol was approved by Ethics Committee of Shanghai Ruijin Rehabilitation Hospital (Approval No. RKIRB2022-12) on February 15, 2022 and was registered with Chinese Clinical Trial Registry (registration number: ChiCTR2200061674; date: June 30, 2022). Study protocol version: 1.0.

Abstract The surface flashover is affected by many factors, such as surface roughness, nanofillers and chemical functional groups. In this research study, polyamide mesh was utilised as a scaffold to systematically study the synergistic effect of micro structure/nanofiller/superhydrophobicity on the surface flashover. Based on the dissolution and resolidification method, nanofillers were partially embedded into the mesh fabrics. Here, Al2O3 nanoparticles were used as a typical non‐conductive nanofiller, and carbon nanotubes were used as a typical conductive nanofiller. Moreover, the micro structure was determined by altering the mesh size, and chemical fluorination was utilised to change the surface chemical group. It was found that the polyamide mesh with 300# demonstrated best anti‐flashover properties. Chemical fluorination could effectively improve the flashover voltage. By further adjusting the ratio of Al2O3 to carbon nanotubes, the flashover voltage can be increased by up to 30%.

NeRF has garnered extensive attention from researchers due to its impressive performance in three-dimensional scene reconstruction and realistic rendering. It is perceived as a potential pivotal technology for scene reconstruction in fields such as virtual reality and augmented reality. However, most NeRF-related research and applications heavily rely on precise pose data. The challenge of effectively reconstructing scenes in situations with inaccurate or missing pose data remains pressing. To address this issue, we examine the relationship between different resolution encodings and pose estimation and introduce BiResNeRF, a scene reconstruction method based on both low and high-resolution hash encoding modules, accompanied by a two-stage training strategy. The training strategy includes setting different learning rates and sampling strategies for different stages, designing stage transition signals, and implementing a smooth warm-up learning rate scheduling strategy after the phase transition. The experimental results indicate that our method not only ensures high synthesis quality but also reduces training time. Compared to other algorithms that jointly optimize pose, our training process is sped up by at least 1.3×. In conclusion, our approach efficiently reconstructs scenes under inaccurate poses and offers fresh perspectives and methodologies for pose optimization research in NeRF.

BackgroundsThe safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.MethodsThis network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.ResultsNine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.ConclusionIn patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient’s profiles to maximize safety.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022334644.

Acute myocardial ischemia is a disease with high morbidity and mortality, and re-perfusion is currently the best intervention. However, re-perfusion may lead to further myocardial injury and increase the area of myocardial infarction. The mechanism of myocardial ischemia-re-perfusion injury is complex, but with more in-depth study, it has been proved that the immune system plays an important role in the process of MIRI. Among them, the γδT cell population has received increasing attention as the main early source of IL-17A in many immune response models. Because γδT cells have the characteristics of linking innate immunity and adaptive immunity,they can rapidly produce IL-17A and produce subsequent immune killing of cardiomyocytes. It can be seen that γδT cells play an important role in MIRI. Therefore, here we review the research progress of immune response in myocardial ischemia-re-perfusion injury, the key characteristics of γδT cells and the role of rapidly produced IL-17 in myocardial ischemia-re-perfusion injury, and propose relevant treatment strategies and prospects for myocardial repair, in order to provide new ideas and methods for clinical treatment of myocardial ischemia-re-perfusion injury.

Keratin (K) and other intermediate filament (IF) protein mutations at conserved arginines disrupt keratin filaments into aggregates and cause human epidermolysis bullosa simplex (EBS; K14-R125C) or predispose to mouse liver injury (K18-R90C). The challenge for more than 70 IF-associated diseases is the lack of clinically utilized IF-targeted therapies. We used high-throughput drug screening to identify compounds that normalized mutation-triggered keratin filament disruption. Parthenolide, a plant sesquiterpene lactone, dramatically reversed keratin filament disruption and protected cells and mice expressing K18-R90C from apoptosis. K18-R90C became hyperacetylated compared with K18-WT and treatment with parthenolide normalized K18 acetylation. Parthenolide upregulated the NAD-dependent SIRT2, and increased SIRT2-keratin association. SIRT2 knockdown or pharmacologic inhibition blocked the parthenolide effect, while site-specific Lys-to-Arg mutation of keratin acetylation sites normalized K18-R90C filaments. Treatment of K18-R90C–expressing cells and mice with nicotinamide mononucleotide had a parthenolide-like protective effect. In 2 human K18 variants that associate with human fatal drug-induced liver injury, parthenolide protected K18-D89H– but not K8-K393R–induced filament disruption and cell death. Importantly, parthenolide normalized K14-R125C–mediated filament disruption in keratinocytes and inhibited dispase-triggered keratinocyte sheet fragmentation and Fas-mediated apoptosis. Therefore, keratin acetylation may provide a novel therapeutic target for some keratin-associated diseases.

IntroductionThe clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir.MethodsA total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development.ResultsOf the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment.DiscussionIn conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).

As an important part of business English practice teaching, this study explores the design and implementation of business negotiation simulation in a Chinese university context with 77 English-major participants, using online surveys and written document analyses. The English-major participants were satisfied with the approach used in the design of the business negotiation simulation, which mostly used real-world cases in the international context. The participants considered teamwork and group cooperation to be their most improved skills, along with other soft skills and practice abilities. Most of the participants reported that the business negotiation simulation directly reflected the real-world scenarios. Most of the participants ranked the negotiation process as the best sessions, followed up by preparation, group cooperation and discussion. Regarding areas of improvement, the participants needed more rehearsal and practice, more examples of negotiation, more guidance from the teacher on case selection and grouping, feedback from the teacher and the incorporation of simulation activities in offline classroom teaching settings.

Biochar has received increased research attention due to its effectiveness in mitigating the potential risks of mercury (Hg) in agricultural soils. However, there is a lack of consensus on the effect of pristine biochar on the net production, availability, and accumulation of methylmercury (MeHg) in the paddy rice-soil system. As such, a meta-analysis with 189 observations was performed to quantitatively assess the effects of biochar on Hg methylation, MeHg availability in paddy soil, and the accumulation of MeHg in paddy rice. Results suggested that biochar application could significantly increase the production of MeHg in paddy soil by 19.01%; biochar could also decrease the dissolved and available MeHg in paddy soil by 88.64% and 75.69%, respectively. More importantly, biochar application significantly inhibited the MeHg accumulation in paddy rice by 61.10%. These results highlight that biochar could decrease the availability of MeHg in paddy soil and thus inhibit MeHg accumulation in paddy rice, although it might facilitate the net production of MeHg in paddy soil. Additionally, results also indicated that the biochar feedstock and its elementary composition significantly impacted the net MeHg production in paddy soil. Generally, biochar with a low carbon content, high sulfur content, and low application rate might be beneficial for inhibiting Hg methylation in paddy soil, meaning that Hg methylation depends on biochar feedstock. These findings suggested that biochar has great potential to inhibit MeHg accumulation in paddy rice, and further research should focus on selecting biochar feedstock to control Hg methylation potential and determine its long-term effects.

Abstract Xikuangshan (XKS) is the world's largest antimony mining region, and its exploitation for hundreds of years has also resulted in serious soil erosion, fragile ecology, contaminated water, and shortage water. Through systematic and scientific collection samples from the rivers in XKS, the Nemerow index (NI), modified heavy metal pollution index (m-HPI), ecological risk index, and health risk indexeswere used to evaluate and analyze the water quality, pollution levels and risks of heavy metals (Sb, As, Mn, Pb, Zn, Hg, Cd) to ecology and humans in XKS. The results showed that the average concentrations of TN, TP, Sb, As and Hg in surface water were 0.48 mg/L (0–4.34 mg/L), 2.58 mg/L (0–4.34 mg/L), 1.05 mg/L (0.0009–5.33 mg/L), 1.06 mg/L (BDL–19.60 mg/L) and 0.00084 mg/L (LDBL–0.0036 mg/L), respectively, exceeding the limits of the Chinese surface water quality standards. Based on the m-HPI method, only 8.57% of the sampling points are classified as the worst water quality. However, according to the NI method, about 7.14% and 87.16% of the sampling points in the study area are moderately and severely polluted, respectively. The results of heavy metal pollution based on the NI evaluation is were more serious than that on the m-HPI method. The values of ecological risk assessment varied from 22.69 to 7351.20, revealed that heavy metals pose a very serious risk to the surface water ecosystem at more than 50% of the sampling sites, and Sb and As are the main pollutants, followed by Hg. The total non-carcinogenic risk index (TCR) for adults and children were 47.70 and 90.10 respectively, Sb and As is the main non-carcinogenic risk factor. For adults and children, the average carcinogenic risk (CR) of As was 6.49 × 10–3 and 1.05 × 10–2, respectively, and exceeded the threshold of 1 × 10–4, indicating a high carcinogenic risk.

Abstract Investigation and assessment of farmland pollution require an efficient method to identify heavy metal (HM) pollutants and their sources. In this study, heavy metals (HMs) in farmland were determined efficiently using high-precision X-ray fluorescence (HDXRF) spectrometer. The potential ecological risk and health risk of HMs in farmland near eight villages of Wushan County in China were quantified using an integrated method of concentration-oriented risk assessment (CORA) and source-oriented risk assessment (SORA). The CORA results showed that Cd in farmland near the villages of Liuping (LP) and Jianping (JP) posed a “very high” potential ecological risk, which is mainly ascribed to soil Cd (single potential ecological risk index ( $${E}_{r}^{i}$$ E r i ) of Cd in villages LP and JP, $${E}_{r}^{i}$$ E r i = 2307 and 568 > 320). A “moderate” potential ecological risk was present in other six villages. The overall non-carcinogenic risk (hazard index (HI) = 1.2 > 1) of HMs for children in village LP was unacceptable. The contributions of HMs decrease in the order of Cr > As > Cd > Pb > Ni > Cu > Zn. The total carcinogenic risk (TCR = 2.1 × 10–4 > 1.0 × 10–4) of HMs in village LP was unacceptable, with HMs contributions decreasing in the order of Cr > Ni > Cd > As > Pb. Furthermore, three source profiles were assigned by the positive matrix factorization: F1: agricultural activity; F2: geological anomaly originating from HMs-rich rocks; F3: the natural geological background. According to the results of SORA, F2 was the highest contributor to PER in village LP, up to 64.4%. Meanwhile, the contributions of three factors to HI in village LP were 19.0% (F1), 53.6% (F2), and 27.4% (F3), respectively. It is worth noting that TCR (1.2 × 10–4) from F2 surpassed the threshold of 1.0 × 10–4, with an unacceptable carcinogenic risk level. As mentioned above, the HM pollutants (i.e., Cd and Cr) and their main sources (i.e., F2) in this area should be considered. These results show that an integrated approach combining risk assessments with the determination of HM concentration and identification of HM source is effective in identifying HM pollutants and sources and provides a good methodological reference for effective prevention and control of HM pollution in farmland.

Iron plaque, naturally iron-manganese (hydr)oxides adhered to the surface of rice roots, controls the sequestration and accumulation of arsenic (As) and cadmium (Cd) in the paddy soil-rice system. However, the effects of the paddy rice growth on the iron plaque formation and As and Cd accumulation of rice roots are often neglected. This study explores the distribution characteristics of iron plaques on rice roots and their effects on As and Cd sequestration and uptake via cutting the rice roots into 5 cm segments. Results indicated that the percentages of rice root biomass of 0–5 cm, 5–10 cm, 10–15 cm, 15–20 cm, and 20–25 cm are 57.5 %, 25.2 %, 9.3 %, 4.9 %, and 3.1 %, respectively. Iron (Fe) and manganese (Mn) concentrations in iron plaques on rice roots of various segments are 41.19–81.11 g kg−1 and 0.94–3.20 g kg−1, respectively. Increased tendency of Fe and Mn concentrations from the proximal rice roots to the distal rice roots show that iron plaque is more likely to deposit on the distal rice roots than proximal rice roots. The DCB-extractable As and Cd concentrations of rice roots with various segments are 694.63–1517.23 mg kg−1 and 9.00–37.58 mg kg−1, displaying a similar trend to the distribution characteristics of Fe and Mn. Furthermore, the average transfer factor (TF) of As (0.68 ± 0.26) from iron plaque to rice roots was significantly lower than that of Cd (1.57 ± 0.19) (P 0.05). These results indicated that the formed iron plaque might act as a barrier to As uptake by rice roots and a facilitator to Cd uptake. This study provides insight into the role of iron plaque in the sequestration and uptake of As and Cd in paddy soil-rice systems.