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Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes. Methods A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann–Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation. Results Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P

Abstract Camellia crapnelliana Tutch., belonging to the Theaceae family, is an excellent landscape tree species with high ornamental values. It is particularly an important woody oil-bearing plant species with high ecological, economic, and medicinal values. Here, we first report the chromosome-scale reference genome of C. crapnelliana with integrated technologies of SMRT, Hi-C and Illumina sequencing platforms. The genome assembly had a total length of ~2.94 Gb with contig N50 of ~67.5 Mb, and ~96.34% of contigs were assigned to 15 chromosomes. In total, we predicted 37,390 protein-coding genes, ~99.00% of which could be functionally annotated. The chromosome-scale genome of C. crapnelliana will become valuable resources for understanding the genetic basis of the fatty acid biosynthesis, and greatly facilitate the exploration and conservation of C. crapnelliana.

Abstract This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.

Mustard sprouts is a new form of vegetable product that is gaining attention due to its high content of health-promoting compounds such as glucosinolates. This study investigated the effects of different light qualities (white, red, and blue) alone and in combination with 100 μmol L−1 melatonin on the growth and health-promoting substance content of mustard sprouts. The results showed that white light + melatonin treatment promoted the accumulation of glucosinolates in sprouts (compared with white light increased by 47.89%). The edible fresh weight of sprouts treated with red light + melatonin was the highest, followed by white light + melatonin treatment. In addition, the sprouts treated with blue light + melatonin contained more ascorbic acid, flavonoids, and total phenolics. Therefore, the combined treatment of light quality (especially white light) and melatonin can provide a new strategy to improve the quality of mustard sprouts.

Background: Ovarian cancer has brought serious threats to female health. CCAAT/enhancer binding proteins (C/EBPs) are key transcription factors involved in ovarian cancer. Therefore, comprehensive profiling C/EBPs in ovarian cancer is needed. Methods: A comprehensive analysis concerning C/EBPs in ovarian cancer was performed. Firstly, detailed expression of C/EBP family members was integrally retrieved and then confirmed using immunohistochemistry. The regulatory effects and transcription regulatory functions of C/EBPs were studied by using regulatory network analysis and enrichment analysis. Using survival analysis, receiver operating characteristic curve analysis, and target-disease association analysis, the predictive prognostic value of C/EBPs on survival and drug responsiveness was systematically evaluated. The effects of C/EBPs on tumor immune infiltration were also assessed. Results: Ovarian cancer tissues expressed increased CEBPA, CEBPB, and CEBPG but decreased CEBPD when compared with normal control tissues. The overall alteration frequency of C/EBPs in ovarian cancer was approaching 30%. C/EBP family members formed a reciprocal regulatory network involving carcinogenesis and had pivotal transcription regulatory functions. C/EBPs could affect survival of ovarian cancer and correlated with poor survival outcomes (OS: HR = 1.40, P = .0053 and PFS: HR = 1.41, P = .0036). Besides, expression of CEBPA, CEBPB, CEBPD, and CEBPE could predict platinum and taxane responsiveness of ovarian cancer. C/EBPs also affected immune infiltration of ovarian cancer. Conclusions: C/EBPs were closely involved in ovarian cancer and exerted multiple biological functions. C/EBPs could be exploited as prognostic and predictive biomarkers in ovarian cancer.

Abstract Background Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) hold great therapeutic potential in regenerative medicine. Therefore, it is crucial to establish a Good Manufacturing Practice (GMP)-compliant methodology for the isolation and culture of WJ-MSCs. Through comprehensive research, encompassing laboratory-scale experiments to pilot-scale studies, we aimed to develop standardized protocols ensuring the high yield and quality of WJ-MSCs manufacturing. Methods Firstly, optimization of parameters for the enzymatic digestion method used to isolate WJ-MSCs was conducted. These parameters included enzyme concentrations, digestion times, seeding densities, and culture media. Additionally, a comparative analysis between the explant method and the enzymatic digestion method was performed. Subsequently, the consecutive passaging of WJ-MSCs, specifically up to passage 9, was evaluated using the optimized method. Finally, manufacturing processes were developed and scaled up, starting from laboratory-scale flask-based production and progressing to pilot-scale cell factory-based production. Furthermore, a stability study was carried out to assess the storage and use of drug products (DPs). Results The optimal parameters for the enzymatic digestion method were a concentration of 0.4 PZ U/mL Collagenase NB6 and a digestion time of 3 h, resulting in a higher yield of P0 WJ-MSCs. In addition, a positive correlation between the weight of umbilical cord tissue and the quantities of P0 WJ-MSCs has been observed. Evaluation of different concentrations of human platelet lysate revealed that 2% and 5% concentrations resulted in similar levels of cell expansion. Comparative analysis revealed that the enzymatic digestion method exhibited faster outgrowth of WJ-MSCs compared to the explant method during the initial passage. Passages 2 to 5 exhibited higher viability and proliferation ability throughout consecutive passaging. Moreover, scalable manufacturing processes from the laboratory scale to the pilot scale were successfully developed, ensuring the production of high-quality WJ-MSCs. Multiple freeze-thaw cycles of the DPs led to reduced cell viability and viable cell concentration. Subsequent thawing and dilution of the DPs resulted in a significant decrease in both metrics, especially when stored at 20–27 °C. Conclusion This study offers valuable insights into optimizing the isolation and culture of WJ-MSCs. Our scalable manufacturing processes facilitate the large-scale production of high-quality WJ-MSCs. These findings contribute to the advancement of WJ-MSCs-based therapies in regenerative medicine.

Abstract Background Concurrent follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)was reported in some studies, while the diagnosis of TdT (terminal deoxynucleotydil transferase) positive high grade B cell lymphoma (HGBL) with MYC and BCL2 rearrangements (“double hit”) transformed from FL/DLBCL has been rarely reported. Herein, we described the clinical features and mutation profiles of a case diagnosed with TdT positive “double hit” HGBL following the treatment of FL/DLBCL. Case presentation This is a 43-year-old Chinese man who was diagnosed with low grade FL (account for 80%) combined with DLBCL (20%) at a stage of IVB. The patient presented with BCL2/IGH translocation without MYC rearrangement, as well as the expressions of CD20, CD19, CD10 and BCL2 at the initial diagnosis of FL/DLBCL. MYC rearrangement and TdT expression occurred after the treatment. The targeted sequencing revealed mutations in KMT2D, FOXO1, CREBBP, ATM, STAT6, BCL7A, DDX3X, MUC4, FGFR3, ARID5B, DDX11 and PRKCSH genes were the co-mutations shared by the FL/DLBCL and TdT positive “double hit” HGBL, while CCND3, BIRC6, ROBO1 and CHEK2 mutations specifically occurred after the treatment. The overall survival time was 37.8 and 17.8 months after the initial diagnosis of FL/DLBCL and TdT positive “double hit” HGBL, respectively. Conclusion This study reports a rare case of TdT positive “double hit” HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive “double hit” HGBL transformed from FL/DLBCL.

Transmembrane transport remains a significant challenge for nucleic acid vaccine vectors. Promoting the ability of immune cells, such as macrophages, to capture foreign stimuli is also an effective approach to improving cross-presentation. In addition, polyethyleneimine (PEI) has gained attention in the field of nucleic acid vaccine carriers due to its excellent gene transfection efficiency and unique proton buffering effect. However, although high molecular weight PEI exhibits high efficiency, its high-density positive charges make it highly toxic, which limits its application. In this study, mannose/stearyl chloride functionalized polyethylenimine (SA-Man-PEI) was prepared by functionalizing PEI (molecular weight of 25 kDa) with mannose with immunomodulatory and phagocyte targeting effects, and an alkyl hydrophobic chain segment, which could easily promote cell uptake. Moreover, the functionalized-PEI retains a strong proton buffering effect, which helps the carrier escape from the lysosome. The particle sizes of the composite particles formed by SA-Man-PEI and ovalbumin (OVA) were below 200 nm, with good storage stability at both 4 °C and 37 °C. At a drug concentration of 2 μg/mL, the cell survival rate of functionalized-PEI was 19.2% higher than that of unfunctionalized PEI. In vitro macrophage endocytosis experiments showed that SA-Man-PEI could significantly enhance the macrophage uptake of composite particles, compared to unfunctionalized PEI or single-functionalized PEI. This study offers a new approach for developing PEI as a nucleic acid vaccine carrier, which could simultaneously enhance cell targeting and promote cell uptake.

The gut fungi play important roles in human health and are involved in energy metabolism. This study aimed to examine gut mycobiome composition in obese subjects in two geographically different regions in China and to identify specific gut fungi associated with obesity. A total of 217 subjects from two regions with different urbanization levels [Hong Kong (HK): obese, n = 59; lean, n = 59; Kunming (KM): obese, n = 50; lean, n = 49. Mean body mass index (BMI) for obesity = 33.7] were recruited. We performed deep shotgun metagenomic sequencing on fecal samples to compare gut mycobiome composition and trophic functions in lean and obese subjects across these two regions. The gut mycobiome of obese subjects in both HK and KM were altered compared to those of lean subjects, characterized by a decrease in the relative abundance of Nakaseomyces, Schizosaccharomyces pombe, Candida dubliniensis and an increase in the abundance of Lanchanceathermotolerans, Saccharomyces paradox, Parastagonospora nodorum and Myceliophthorathermophila. Reduced fungal – bacterial and fungal – fungal correlations as well as increased negative fungal-bacterial correlations were observed in the gut of obese subjects. Furthermore, the anti-obesity effect of fungus S. pombe was further validated using a mouse model. Supplementing high-fat diet-induced obese mice with the fungus for 12 weeks led to a significant reduction in body weight gain (p

Parkinson’s disease (PD) is a chronic neurodegenerative disease with unclear pathogenesis that involves neuroinflammation and intestinal microbial dysbiosis. Intercellular adhesion molecule-1 (ICAM-1), an inflammatory marker, participates in neuroinflammation during dopaminergic neuronal damage. However, the explicit mechanisms of action of ICAM-1 in PD have not been elucidated. We established a subacute PD mouse model by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and observed motor symptoms and gastrointestinal dysfunction in mice. Immunofluorescence was used to examine the survival of dopaminergic neurons, expression of microglial and astrocyte markers, and intestinal tight junction-associated proteins. Then, we use 16 S rRNA sequencing to identify alterations in the microbiota. Our findings revealed that ICAM-1-specific antibody (Ab) treatment relieved behavioural defects, gastrointestinal dysfunction, and dopaminergic neuronal death in MPTP-induced PD mice. Further mechanistic investigations indicated that ICAM-1Ab might suppress neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra and relieving colon barrier impairment and intestinal inflammation. Furthermore, 16 S rRNA sequencing revealed that the relative abundances of bacterial Firmicutes, Clostridia, and Lachnospiraceae were elevated in the PD mice. However, ICAM-1Ab treatment ameliorated the MPTP-induced disorders in the intestinal microbiota. Collectively, we concluded that the suppressing ICAM-1 might lead to the a significant decrease of inflammation and restore the gut microbial community, thus ameliorating the damage of DA neurons.

BackgroundIn the medical field, effective time management by clinical nurses is crucial for enhancing the quality of patient care. However, in recent years, with increasing work pressure for clinical nurses, procrastination has become a prevalent issue. Many nurses use smartphones as a way to alleviate stress and manage emotions, but excessive smartphone use could exacerbate procrastination, thereby jeopardizing patient safety and healthcare quality. Therefore, understanding the current state of work procrastination among clinical nurses, its heterogeneity, and exploring the impact of smartphone addiction and demographic factors on different aspects of nurse procrastination hold significant importance for improving patient care quality.ObjectiveThis study aims to explore the current state of work procrastination among clinical nurses and identify potential profile categories. It further analyzes the impact of mobile phone addiction and demographic factors on work procrastination among clinical nurses.MethodsConvenience sampling was employed to recruit participants from three tertiary hospitals in central China from October to November 2023. Surveys measuring nurses’ work procrastination and smartphone addiction were distributed and collected through online platforms. A total of 1,536 nurses participated in this study. Mplus 8.3 statistical software was used for latent profile analysis of clinical nurses’ work procrastination, and SPSS 26.0 software was utilized for chi-square tests, rank-sum tests, and multi-classification logistic regression analyses.ResultsThe median total score for clinical nurses’ work procrastination was 21.00 (17.00, 28.00), and three subgroups were identified: low procrastination (66.93%), medium-low procrastination (20.66%), and medium-high procrastination (12.41%). Additionally, logistic regression analysis revealed that smartphone addiction and department atmosphere were common influencing factors for medium-low and medium-high work procrastination. Hospitals with stricter management and nurses holding the position of head nurse were more likely to belong to the low work procrastination group. Nurses with higher incomes or those holding intermediate titles were more prone to medium-low work procrastination, while those experiencing career advancement difficulties were more likely to exhibit medium-high work procrastination (p

IntroductionIn the aftermath of the pandemic, the impact of health shocks on household expenditure patterns has become a critical area of focus due to the heightened uncertainty surrounding consumers’ expectations. Household medical expenditures have emerged as a key factor in the evolving consumption structure.MethodThis research developed a practical framework to assess the influence of health shocks on family spending patterns, focusing on health shortfalls. Health emergencies were measured through randomized medical spending. Data was sourced from the 2010-2018 Wave 5 Statistical Report of the China Family Panel Studies (CFPS), which included a total of 25,809 participants.ResultsThe findings revealed that health shocks significantly increased the proportion of household spending on medical expenses. Concurrently, sub-expenditures such as food and education were reduced to varying degrees as households adjusted their consumption patterns to mitigate the impact of health shocks. The effects of these shocks were more pronounced in low-income households and those with health insurance.DiscussionsThe government should take steps to promote public health, reduce the burden of medical expenses resulting from health shocks, and unlock the consumption potential. Additionally, efforts should be made to boost economic growth and systematically upgrade household consumption patterns to effectively cushion the impact of health shocks.

Abstract Autistic children often exhibit atypical brain lateralization of language processing, but it is unclear what aspects of language contribute to this phenomenon. This study employed functional near-infrared spectroscopy to measure hemispheric lateralization by estimating hemodynamic responses associated with processing linguistic and non-linguistic auditory stimuli. The study involved a group of autistic children (N = 20, mean age = 5.8 years) and a comparison group of nonautistic peers (N = 20, mean age = 6.5 years). The children were presented with stimuli with systematically decreasing linguistic relevance: naturalistic native speech, meaningless native speech with scrambled word order, nonnative speech, and music. The results revealed that both groups showed left lateralization in the temporal lobe when listening to naturalistic native speech. However, the distinction emerged between autism and nonautistic in terms of processing the linguistic hierarchy. Specifically, the nonautistic comparison group demonstrated a systematic reduction in left lateralization as linguistic relevance decreased. In contrast, the autism group displayed no such pattern and showed no lateralization when listening to scrambled native speech accompanied by enhanced response in the right hemisphere. These results provide evidence of atypical neural specialization for spoken language in preschool- and school-age autistic children and shed new light on the underlying linguistic correlates contributing to such atypicality at the sublexical level.

Abstract Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn’s disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.

Abstract Exfoliation corrosion (EFC) on extruded Mg-4Li-1Ca alloys as bone implant materials has not been reported. This study aimed to elucidate the degradation mechanism of a corrosion type-exfoliation occurred on an extruded Mg-4Li-1Ca alloy under the interaction of glucose (Glu) and bovine serum albumin (BSA) in Hank’s solution. The alloy microstructure, chemical composition, texture, stress distribution and Volta potential maps were characterized using metallographic microscopy, scanning electron microscopy and electron backscattered diffraction, and scanning Kelvin Probe. The alloy corrosion behavior was investigated via electrochemical testing and hydrogen evolution rate methods. X-ray diffraction, Fourier transform infrared spectrometry, X-ray photoelectron spectrometer, and fluorescence microscopy were used to analyze the corrosion products and the adsorption of the organic molecules. The experimental results indicated that the anodic second phase (Mg2Ca) were distributed in lamellar and rod-like patterns along the extrusion direction of the alloy, a lower Volta potential for Mg2Ca, texture and residual stresses also promote EFC. An increase in Glu concentration exacerbated the EFC, whereas BSA inhibited the EFC of the alloy. Higher Glu concentrations in BSA in turn inhibited EFC since Glu can complex with amino acids in proteins to form Glu-amino acid amides, which promoted protein adsorption and thereby forming a dense protective film on the alloy surface. The preferential dissolution of the Mg2Ca phase particles led to the complexation and adsorption of Glu and protein. This study enriches the understanding of the corrosion types in biomedical Mg-4Li-1Ca alloy and paving the way for enhancing the EFC resistance of the alloy.

Objectives: The liver has an excellent ability to regenerate, and disrupted liver regeneration after various injuries leads to an unfavorable prognosis for patients. In this study, we sought to identify novel therapeutic hallmarks that are associated with yes-associated protein 1 (YAP1)-mediated hepatocyte proliferation during the process of liver regeneration. Methods: Partial hepatectomy was conducted to induce liver regeneration in rats. Primary hepatocytes were isolated and cultured. Hepatocyte proliferation was assessed using immunohistochemistry staining, and expression of YAP1 was detected. RNA sequencing and bioinformatics analysis were used to search for potential regulators of YAP1. The association between ubiquitin-specific peptidase 1 (USP1) and YAP1 was validated using in vivo and in vitro experiments. Results: YAP1 was significantly elevated in regenerative hepatocytes, especially in the nucleus. Knockdown of YAP1 using small interfering RNA or pharmacological inhibition using verteporfin significantly attenuated the proliferation of hepatocytes. The bioinformatics analysis results revealed that USP1 was associated with YAP1-mediated hepatocyte proliferation during liver regeneration. ML-323, a specific inhibitor of USP1-USP1 associated factor 1 (UAF1), significantly decreased the expression of YAP1, Cyclin D1, and proliferating cell nuclear antigen, while these decreased expressions could be rescued by YAP1 overexpression. Furthermore, ML-323 treatment significantly inhibited liver regeneration following partial hepatectomy. Conclusions: In conclusion, we identified USP1 as a novel biomarker that is associated with YAP1-mediated hepatocyte proliferation in liver regeneration. Pharmacological inhibition of USP1 by ML-323 substantially impairs hepatocyte proliferation during liver regeneration.

Abstract Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross‐linked vesicle membranes through the reduction of silver nitrate (AgNO3) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X‐ray diffraction (XRD), ultraviolet‐visible spectroscopy (UV‐vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles. The antibacterial test demonstrated good antibacterial activity against both Gram‐negative bacteria (Escherichia coli) and Gram‐positive bacteria (Staphylococcus aureus) for the produced AgNP‐decorated vesicles. The minimum inhibitory concentration (MIC) values of the AgNP‐decorated vesicles for E. coli and S. aureus were 8.4 and 9.6 μg/mL, respectively. Cell viability analysis on the A549 cells indicated that the toxicity was low when the AgNP concentrations did not exceed the MIC values, and the wound healing test confirmed the good antibacterial properties of the AgNP‐decorated vesicles.

Abstract This work aims to explore the long‐term prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF). In this prospective study, eligible inpatients with HBV‐ACLF are enrolled and followed up from December 2012 to February 2023, for clinical events, laboratory tests at least every 6 months. Overall, the survival rates at 28 days, 90 days, 1 year, 5 years, and 8 years are 64.7%, 48.8%, 46.1%, 43.8%, and 42.2%, respectively. Among the 8‐year mortality and liver transplant cases, ACLF survivors (who survived over 90 days) accounted for 7.8% (9/115). Among 101 patients who survived for more than 90 days, 97.9% of patients achieve virologic response at 1 year. For HBeAg‐positive patients, the HBeAg seroconversion are 25.5%, 63.6%, and 76.9% at 1, 5, and 8 years, respectively. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR, white blood cell count, and albumin levels gradually improve within the first year. Fibrosis biomarkers APRI, FIB‐4 and Chitinase‐3‐like protein 1 (CHI3L1) levels decreases within the first 5 years. The Cox proportional hazards regression reveal that high total bilirubin (HR = 1.008, p = 0.021) is the independent risk factor for 8‐year survival of ALCF survivors. The 90‐day period following of HBV‐ACLF represented a critical juncture for long‐term prognosis, revealing favorable outcomes beyond this timeframe.

Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic synovitis and bone destruction. Proinflammatory cytokines activate pathways of immune-mediated inflammation, which aggravates RA. The mechanistic target of rapamycin (mTOR) signaling pathway associated with RA connects immune and metabolic signals, which regulates immune cell proliferation and differentiation, macrophage polarization and migration, antigen presentation, and synovial cell activation. Therefore, therapy strategies targeting mTOR have become an important direction of current RA treatment research. In the current review, we summarize the biological functions of mTOR, its regulatory effects on inflammation, and the curative effects of mTOR inhibitors in RA, thus providing references for the development of RA therapeutic targets and new drugs.

In this study, the effects of intermetallic compounds (Mg17Al12 and Al8Mn5) on the Mg-Al layered double hydroxide (LDH) formation mechanism and corrosion behavior of an in-situ LDH/Mg(OH)2 steam coatings on AZ80 Mg alloy were investigated. Citric acid (CA) was used to activate the alloy surface during the pretreatment process. The alloy was first pretreated with CA and then subjected to a hydrothermal process using ultrapure water to produce Mg-Al-LDH/Mg(OH)2 steam coating. The effect of different time of acid pretreatment on the activation of the intermetallic compounds was investigated. The microstructure and elemental composition of the obtained coatings were analyzed using FE-SEM, EDS, XRD and FT-IR. The corrosion resistance of the coated samples was evaluated using different techniques, i.e., potentiodynamic polarization (PDP), electrochemical impedance spectrum (EIS) and hydrogen evolution test. The results indicated that the CA pretreatment significantly influenced the activity of the alloy surface by exposing the intermetallic compounds. The surface area fraction of Mg17Al12 and Al8Mn5 phases on the surface of the alloy was significantly higher after the CA pretreatment, and thus promoted the growth of the subsequent Mg-Al-LDH coatings. The CA pretreatment for 30 s resulted in a denser and thicker LDH coating. Increase in the CA pretreatment time significantly led to the improvement in corrosion resistance of the coated AZ80 alloy. The corrosion current density of the coated alloy was lower by three orders of magnitude as compared to the uncoated alloy.

Pigments derived from red pepper fruits are widely used in food and cosmetics as natural colorants. Nitrogen (N) is a key nutrient affecting plant growth and metabolism; however, its regulation of color-related metabolites in pepper fruit has not been fully elucidated. This study analyzed the effects of N supply (0, 250, and 400 kg N ha-1) on the growth, fruit skin color, and targeted and non-target secondary metabolites of field-grown pepper fruits at the mature red stage. Overall, 16 carotenoids were detected, of which capsanthin, zeaxanthin, and capsorubin were the dominant ones. N application at 250 kg ha-1 dramatically increased contents of red pigment capsanthin, yellow-orange zeaxanthin and β-carotene, with optimum fruit yield. A total of 290 secondary metabolites were detected and identified. The relative content of most flavonoids and phenolic acids was decreased with increasing N supply. Correlation analysis showed that color parameters were highly correlated with N application rates, carotenoids, flavonoids, phenolic acids, lignans, and coumarins. Collectively, N promoted carotenoid biosynthesis but downregulated phenylpropanoid and flavonoid biosynthesis, which together determined the spectrum of red color expression in pepper fruit. Our results provide a better understanding of the impact of N nutrition on pepper fruit color formation and related physiology, and identification of target metabolites for enhancement of nutritional quality and consumer appeal.

AbstractPost-encapsulation and release of the anticancer drug doxorubicin hydrochloride (DOX·HCl) through cell-like transmission functions of polymeric vesicles were studied using cross-linked pH-responsive polymeric vesicles. The vesicles were fabricated for the first time via the redox-initiated reversible addition-fragmentation chain transfer dispersion polymerization in ethanol-water mixture, using 2-(diisopropylamino)ethyl methacrylate and glycidyl methacrylate, and the vesicle membrane was modified post-cross-linking by using ethylenediamine. A phase diagram was constructed for reproducible fabrication of the polymeric vesicles, and well-shaped vesicles were formed when the target degree of polymerization of the hydrophobic polymer chains was equal to or higher than 50 with solid content in the range of 10–30 wt%. The cross-linked vesicle membrane served as a gate enabling “open” and “closed” states in response to pH stimulation. Up to 50% drug loading efficiency and 39% drug loading content could be achieved, and in vitro release of the DOX-loaded vesicles in aqueous buffer solutions showed a much faster DOX release rate at pH 5.0 than at pH 6.5. The polymeric vesicles were of very low cytotoxicity to A549 cells up to the concentration of 2 mg/mL, and the IC50 of DOX-loaded vesicles were higher than that of the free DOX. The intracellular DOX release study indicated higher cellular uptake capability for DOX-loaded vesicles than that of free DOX.

Layered double hydroxide (LDH) coatings on magnesium (Mg) alloys shine brightly in the field of corrosion protection because of their special ion-exchange function. State-of-the-art steam coating as a type of LDH film preparation technique has emerged in recent years because only pure water is required as the steam source and its environmentally friendly LDH coating fits the current need for green development. Moreover, this coating can effectively inhibit the corrosion of the Mg alloy substrate due to the chemical bonding between the coating and the Mg alloy substrate. This review systematically explains cutting-edge advancements in the growth mechanism and corrosion behavior of LDH steam coatings, and analyzes the advantages and limitations of the steam-coating method. The influencing factors including pressure, CO2/CO32−, aluminum content of the substrate alloy, solution type, and acid-pickling pretreatment, as well as the post-treatment of steam-coating defects, are comprehensively elucidated, providing new insights into the development of the in situ steam-coating technique. Finally, existing issues and future prospects are discussed to further accelerate the widespread application of Mg alloys.

A series of methods such as the high performance liquid chromatography and amino acid analyzer were used to study the effects of different drying temperatures (60, 75, 90 and 105 ℃) on the protein, amino acids, fatty acids and other quality components of ziziphi spinosae folium insect tea (ZSIT). The results showed that polyphenols and total amino acids of ZSIT dried at 90 ℃ with the highest total flavonoids and essential amino acids were significantly higher than those of other groups (P

In recent years, oxygen vacancy (VO) engineering has become a research hotspot in the field of photocatalysis. Herein, an efficient GQDs/BiOCl-VO heterojunction photocatalyst was fabricated by loading graphene quantum dots (GQDs) onto BiOCl nanosheets containing oxygen vacancies. ESR and XPS characterizations confirmed the formation of oxygen vacancy. Combining experimental analysis and DFT calculations, it was found that oxygen vacancy promoted the chemical adsorption of O2, while GQDs accelerated electron transfer. Benefiting from the synergistic effect of oxygen vacancy, GQDs, and dye sensitization, the as-prepared GQDs/BiOCl-VO sample exhibited improved efficiency for RhB degradation under visible-light irradiation. A 2 wt% GQDs/BiOCl-VO composite effectively degraded 98% of RhB within 20 min. The main active species were proven to be hole (h+) and superoxide radical (·O2−) via ESR analysis and radical trapping experiments. This study provided new insights into the effective removal of organic pollutants from water by combining defect engineering and quantum dot doping techniques in heterojunction catalysts.

Basella alba is a frequently consumed leafy vegetable. However, research on its nutritional components is limited. This study aimed to explore the variation in the nutritional components and antioxidant capacity of different cultivars and organs of Basella alba. Here, we primarily chose classical spectrophotometry and high-performance liquid chromatography (HPLC) to characterize the variation in nutritional components and antioxidant capacity among different organs (inflorescences, green fruits, black fruits, leaves, and stems) of eight typical cultivars of Basella alba. The determination indices (and methods) included the total soluble sugar (anthrone colorimetry), total soluble protein (the Bradford method), total chlorophyll (the ethanol-extracting method), total carotenoids (the ethanol-extracting method), total ascorbic acid (the HPLC method), total proanthocyanidins (the p-dimethylaminocinnamaldehyde method), total flavonoids (AlCl3 colorimetry), total phenolics (the Folin method), and antioxidant capacity (the FRAP and ABTS methods). The results indicated that M5 and M6 exhibited advantages in their nutrient contents and antioxidant capacities. Additionally, the inflorescences demonstrated the highest total ascorbic acid and total phenolic contents, while the green and black fruits exhibited relatively high levels of total proanthocyanidins and antioxidant capacity. In a comparison between the green and black fruits, the green fruits showed higher levels of total chlorophyll (0.77–1.85 mg g−1 DW), total proanthocyanidins (0.62–2.34 mg g−1 DW), total phenolics (15.28–27.35 mg g−1 DW), and ABTS (43.39–59.16%), while the black fruits exhibited higher levels of total soluble protein (65.45–89.48 mg g−1 DW) and total soluble sugar (56.40–207.62 mg g−1 DW) in most cultivars. Chlorophyll, carotenoids, and flavonoids were predominantly found in the leaves of most cultivars, whereas the total soluble sugar contents were highest in the stems of most cultivars. Overall, our findings underscore the significant influence of the cultivars on the nutritional composition of Basella alba. Moreover, we observed notable variations in the nutrient contents among the different organs of the eight cultivars, and proanthocyanidins may contribute significantly to the antioxidant activity of the fruits. On the whole, this study provides a theoretical basis for the genetic breeding of Basella alba and dietary nutrition and serves as a reference for the comprehensive utilization of this vegetable.

Research into leaf traits, especially carbon (C), nitrogen (N), and phosphorus (P), are essential for understanding the nutrient uptake strategies and ecosystem functions, such as the rates of photosynthesis, transpiration, and nutrient intake in plants. However, seasonal patterns of leaf C:N:P stoichiometry in arid and semiarid forest ecosystems remain unclear. In this study, temporal scale monitoring was conducted on four conifer species (Picea wilsonii, Pinus tabuliformis, Picea crassifolia, and Juniperus przewalskii) within the Qilian Mountains to determine the seasonal patterns of leaf C:N:P stoichiometry and their driving forces. The seasonal patterns of the leaf N and P contents were asynchronous among the species. The C content and C:N and C:P ratios in the leaves in Tulugou (relatively wet and fertile) were lower than those in Langchaigou (extremely infertile and dry), whereas the N and P contents in the leaves displayed an inverse pattern (p

Abstract Objective To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy. Methods The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non‐PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery. Results Three patients in the non‐PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non‐PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non‐PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased. Conclusions The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have not yet been elucidated. Our study aimed to investigate the correlation between gut microbiota disturbances and feces metabolic disorders in PD. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models and observed mice's motor symptoms, dopaminergic (DA) neuron death, and gastrointestinal dysfunction. To identify alterations in microbiota and metabolome, feces were collected from mice and analyzed using 16 S ribosomal RNA sequencing feces metabolomics. Pearson analysis was utilized to investigate correlations between the abundances of gut microbiota components and the levels of gut microbiota metabolites, displaying their interaction networks. Our findings revealed a significant increase in Desulfobacterota in the PD mouse model and 151 differentially expressed fecal metabolites between PD and vehicle mice. Moreover, Pearson correlation analysis suggested that the protective factor N-acetyl-L-leucine (NALL) may be associated with neuroinflammation in the striatum and substantia nigra, which also had a negative relationship with the concentration of Desulfobacterota. Additionally, we found that oral administration of NALL alleviated MPTP-induced Motor Impairments and DA neuronal deficits. All in all, we concluded that the decrease of NALL might lead to a significant increase of Desulfobacterota in the MPTP model mouse and subsequently result in the damage of DA neurons via the gut-brain aix pathway.

Abstract Purpose This study aimed to investigate the characteristics of the optic disc in adolescents and young adults with high myopia by applying optical coherence tomography angiography. Methods A total of 112 patients with high myopia (spherical equivalent refraction (SER) ≤ -6.00 D) aged 12 to 30 years old were enrolled in this cross-sectional study. Parapapillary atrophy (PPA) and ovality index from scanning laser ophthalmoscopy images and the degree of optic disc tilt from the optic nerve head (ONH) OCT B-scans were analysed using ImageJ and MATLAB software. Peripapillary retinal nerve fibre layer thickness (pRNFLT) and radial peripapillary capillary vessel density (RPC VD) around the optic disc were obtained from the images of the optic disc angiography scan. Results In young high myopia patients, the PPA area was positively correlated with age, axial length (AL) and pRNFLT (all p

Surgical failures, caused by postoperative infections of bone implants, are commonly met, which cannot be treated precisely with intravenous antibiotics. Photothermal therapy (PTT) and photodynamic therapy (PDT) have attracted widespread attention due to their non-invasive antibacterial effects on tissues and no bacterial resistance, which may be an excellent approach to solve infections related to bone implants for biodegradable magnesium alloys. Herein, a sodium copper chlorophyllin (SCC) with a porphyrin ring induced Ca–P coating was prepared on AZ31 magnesium alloy via layer-by-layer (LbL) assembly. The morphology and composition of the samples were characterized through field emission scanning electron microscope (FE-SEM) with affiliated energy dispersive spectrometer (EDS), X-ray diffractometer (XRD), and Fourier infrared spectrometer (FTIR) and X-ray photoelectron spectrometer (XPS) as well. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and hydrogen evolution experiments were employed to evaluate the corrosion behavior of the samples. Atomic absorption spectrophotometer was used to measure Cu elemental content of different immersion periods. Cytocompatibility and antibacterial performance of the coatings were probed using in vitro cytotoxicity tests (MTT assay), live/dead cell staining and plate counting method. The results showed that the obtained (Ca–P/SCC)10 coating exhibited good corrosion resistance, antimicrobial activity (especially under 808 nm irradiation) and biocompatibility. The antibacterial rates for E. coli and S. aureus were 99.9% and 99.8%, respectively; and the photothermal conversion efficiency was as high as 42.1%. Triple antibacterial mechanisms including photodynamic, photothermal reactions and copper-ions release were proposed. This coating exhibited a promising application for biodegradable magnesium alloys.

Abstract To investigate the impact and factors of home quarantine life on women’s sexual lives and behaviors in different areas of China and analyze the prevalence of female sexual dysfunction (FSD) during the COVID-19 pandemic. We surveyed adult women who had a regular sexual life (including regular masturbation) and had been isolated at home for at least one month during the COVID-19 outbreak using online questionnaires. This survey recovered 678 complete questionnaires after screening. According to the findings, the overall score of the Female Sexual Function Inventory (FSFI) during the pandemic was 21.98 ± 6.38, the frequency of FSD was 61.9%, and the frequencies of FSD in Shanghai, Nanjing, and Ningxia were 60.6%, 75.2%, and 52.2%, respectively. The frequency of FSFI scores and other specific items (Desire, Arousal, Lubrication, Orgasm, Satisfaction, and Pain) varied significantly across the three regions (P

Here, by performing an integrative multi-omics analysis coupled to clinical features of COVID-19 patients prospectively followed for up to 6 month, the authors identify specific gut microbiome patterns associated with disease severity and development of post-acute COVID-19 syndrome.

The main tea characteristic components, volatile components and amino acid composition of insect tea from three main producing areas in Guangxi were analyzed in this paper, and the amino acid characteristics and nutritional value were evaluated by amino acid ratio coefficient method. The results showed that Guangxi insect tea was rich in contents and had the characteristics of low caffeine and high amino acid and there were extremely significant differences in water extracts, amino acids and tea polyphenols of insect tea from different producing areas (P

● Sustainable nitrogen management strategies for Chinese vegetable production are summarized. ● Research on reactive N (Nr) losses in Chinese vegetable systems is limited compared to cereal crop systems. ● Knowledge-based optimization of N fertilizer rate strategy maintains soil N supply to meet the dynamic vegetable demand in time, space and quantity. ● Innovative products and technology strategy regulates the soil N forms and promotes the vegetable root growth to further control the Nr loss. ● Integrated knowledge and products strategy is needed to produce more vegetables with lower Nr losses. Inappropriate nitrogen fertilizer management for the intensive Chinese vegetable production has caused low N use efficiency (NUE), high reactive nitrogen (Nr) losses and serious environmental risks with limited yield increase. Innovative N management strategy is an urgent need to achieve sustainable vegetable production. This paper summarizes recent studies on Nr losses and identifies the limitations from Chinese vegetable production systems and proposes three steps for sustainable N management in Chinese vegetable production. The three N management steps include, but are not limited to, (1) knowledge-based optimization of N fertilizer rate strategy, which maintains soil N supply to meet the dynamic vegetable demand in time, space and quantity; (2) innovative products and technology, which regulates the soil N forms and promotes the vegetable root growth to reduce the Nr loss; (3) integrated knowledge and products strategy (IKPS). The knowledge-based optimization of N fertilizer rate strategy and innovative products and technology, can maintain or increase vegetable yield, significantly improve NUE, and mitigate the region-specific and crop-specific Nr losses. More importantly, IKPS, based on combination of in-season root-zone N management strategy, innovative products and technology, and best crop cultivation management, is needed to produce more vegetables with lower Nr losses.

BackgroundFlurochloridone (FLC) can induce apoptosis in Sertoli cells, but the specific mechanism remains unknown.ObjectiveTo investigate the testicular cell apoptosis in mice as well as apoptosis and activation of endoplasmic reticulum stress in TM4 cell line induced by FLC through in vivo and in vitro study designs respectively, and study the role of inosital-requiring enzyme 1α (IRE1α)-c-Jun N-terminal kinase (JNK) signaling pathway in the process of FLC-induced apoptosis in TM4 cells through intervention study design.MethodsTesticular tissues were collected from male C57BL/6 mice which were treated with 3, 15, 75, and 375 mg·（kg·d）−1 FLC by oral perfusion for 28 d. Apoptosis was observed by TUNEL staining, and the levels of apoptosis-related proteins were detected by Western blotting, including B-cell lymphoma-2 (Bcl-2), Bcl-2 interacting mediator of cell death (Bim), and Bcl-2 associated X protein (Bax). In the in vitro study, TM4 cells were treated with different concentrations of FLC (40, 80, and 160 μmol·L−1) for 6 h, then apoptosis rate was detected by flow cytometry, and the levels of apoptosis-related proteins (Bcl-2, Bim, and Bax) and endoplasmic reticulum stress-related proteins [glucose regulated protein 78 (GRP78), phosphorylated-protein kinase R like endoplasmic reticulum kinase (p-PERK), activating transcription factor 6 (ATF6), phosphorylated-inosital-requiring enzyme 1α (p-IRE1α), and phosphorylated-JNK (p-JNK)] were measured by Western blotting. In the intervention study, TM4 cells were pretreated with IRE1α phosphorylation inhibitor 4μ8C and JNK phosphorylation inhibitor SP600125 for 6 h, then treated with 160 μmol·L−1 FLC for 6 h. The levels of apoptosis-related proteins and endoplasmic reticulum stress-related proteins were measured by Western blotting, and cell viability was detected by cell counting kit-8.ResultsAfter the male C57BL/6 mice orally exposed to FLC for 28 d, apoptosis occurred in the seminiferous tubule. The protein expression level of Bcl-2, apoptosis inhibitor, was decreased in the 75 and 375 mg·(kg·d)−1 groups (P

Melatonin, a pleiotropic small molecule, is employed in horticultural crops to delay senescence and preserve postharvest quality. In this study, 100 µM melatonin treatment delayed a decline in the color difference index h* and a*, maintaining the content of chlorophyll and carotenoids, thereby delaying the yellowing and senescence of Chinese kale. Transcriptome analysis unequivocally validates melatonin’s efficacy in delaying leaf senescence in postharvest Chinese kale stored at 20 °C. Following a three-day storage period, the melatonin treatment group exhibited 1637 differentially expressed genes (DEGs) compared to the control group. DEG analysis elucidated that melatonin-induced antisenescence primarily governs phenylpropanoid biosynthesis, lipid metabolism, plant signal transduction, and calcium signal transduction. Melatonin treatment up-regulated core enzyme genes associated with general phenylpropanoid biosynthesis, flavonoid biosynthesis, and the α-linolenic acid biosynthesis pathway. It influenced the redirection of lignin metabolic flux, suppressed jasmonic acid and abscisic acid signal transduction, and concurrently stimulated auxin signal transduction. Additionally, melatonin treatment down-regulated RBOH expression and up-regulated genes encoding CaM, thereby influencing calcium signal transduction. This study underscores melatonin as a promising approach for delaying leaf senescence and provides insights into the mechanism of melatonin-mediated antisenescence in postharvest Chinese kale.

In China, cadmium (Cd) stress has a significant role in limiting the development and productivity of purple flowering stalks (Brassica campestris var. purpuraria). Exogenous selenium supplementation has been demonstrated in earlier research to mitigate the effects of Cd stress in a range of plant species; nevertheless, the physiological and molecular processes by which exogenous selenium increases vegetable shoots’ resistance to Cd stress remain unclear. Purple flowering stalks (Brassica campestris var. purpuraria) were chosen as the study subject to examine the effects of treatment with sodium selenite (Na2SeO3) on the physiology and transcriptome alterations of cadmium stress. Purple flowering stalk leaves treated with exogenous selenium had higher glutathione content, photosynthetic capacity, and antioxidant enzyme activities compared to the leaves treated with Cd stress alone. Conversely, the contents of proline, soluble proteins, soluble sugars, malondialdehyde, and intercellular CO2 concentration tended to decrease. Transcriptome analysis revealed that 2643 differentially expressed genes (DEGs) were implicated in the response of exogenous selenium treatment to Cd stress. The metabolic pathways associated with flavonoid production, carotenoid synthesis, glutathione metabolism, and glucosinolate biosynthesis were among those enriched in these differentially expressed genes. Furthermore, we discovered DEGs connected to the production route of glucosinolates. This work sheds fresh light on how purple flowering stalks’ tolerance to cadmium stress is improved by exogenous selenium.

The main problem faced by traditional three-dimensional (3D) holographic displays is the time-consuming and poor flexibility of the hologram generation process. To address this issue, this paper proposes a non-iterative 3D computer-generated hologram (SFS-ORAP-PC-3D) method based on single full-support optimized random phase and phase compensation. Combining the full-support optimized random phase (FS-ORAP) method and the 3D layer-based idea to efficiently and non-iteratively generate the phase-only hologram of a 3D object with arbitrary positions and sizes using single FS-ORAP, thus overcoming the limitations of the original ORAP method in target position and size. Meanwhile, using a Fresnel lens for phase compensation allows for free selection of reconstruction planes. Numerical and optical experiments validate the feasibility of our proposed method.

This paper examines the phonetic properties of the degree adverb “hen” in Yuanjiang dialect (YJD hereafter) with empirical data from local people. Three sets of parameters, i.e. fundamental frequency (F0), duration and tone value (T-value), were analyzed. The degree adverb “hen” in YJD can be used as not only an adverbial but also a complement, and the sound of “hen” varies with syntactic functions and semantics. The results show that “hen” as an adverbial can be read as both “[xei45]” which means “very” and “[xei21]” which implies nearly no practical meaning, and that “hen” being a complement is uttered as “[xei41]”, indicating the meaning of “very” but carrying higher degree and stronger intonation than “[xei45]”. According to phonetic experiments, the sound change of “hen” in YJD lies in the change of tone value without transforming the initial consonant and vowel. Such phonetic phenomenon of ‘‘hen” in YJD is neither literal and colloquial readings nor tone sandhi, but a polyphonic phenomenon caused by internal inflexion.

Abstract The northern fringe area of the East Asian summer monsoon (EASM) between arid and semiarid regions is a fragile eco-environment zone and ecological transition zone, and it is highly sensitive to climate change. Predicting the future migration of the northern boundary of the EASM is important for understanding future East Asian climate change and formulating of decisions on ecological protection and economic development in arid and semiarid regions. The reanalysis dataset and simulations of 23 models from the Coupled Models Intercomparison Project Phase 6 (CMIP6) were used to investigate the response of the boundary of the ESAM to the global warming. The multi-model ensemble showed a northwestward migration of the EASM northern boundary during the near-term (2020–2060) and late-term (2061–2099) of the twenty-first century under various Shared Socioeconomic Pathways (SSPs). The northern boundary migrated northwestward by 23–28 and 74–76 km in the near-term and late-term respectively, under SSP1-2.6, 2-4.5 and 3-7.0 and by ~ 44 km and ~ 107 km respectively during the near-term and late-term under SSP5-8.5. During the twenty-first century, under various SSPs, the surface of the East Asian subcontinent warmed more than the ocean, thereby increasing the contrast of near-surface temperature and sea level pressure in summer between the East Asian subcontinent and the surrounding oceans. In turn, the intensified land–sea thermal contrast reinforced the EASM meridional circulation and thus transported more moisture from the Indian Ocean into northern China. Additionally, a poleward migration and weakening of the East Asian subtropical westerly jet would also favor an increase in precipitation, eventually caused a northwestward migration of the EASM northern boundary. The results suggest that the arid and semiarid ecotone will become wetter, which could dramatically improve the eco-environment in the future.

Molecular recognition was utilized to fabricate bioinspired calcium phosphate (Ca-P) coating on bioabsorbable magnesium alloys through small biomolecules such as Vitamin C (VC). Ca-P and VC hybrid coating (Ca-PVC) was successfully fabricated on AZ31 Mg alloy. The surface morphology and chemical composition of the coatings were investigated using SEM, XRD, and FTIR together with XPS. The results showed that the Ca-PVC coating was composed of bamboo leaf-like Ca-P particles with a thickness of about three times that of the Ca-P coating. The surface roughness of the Ca-PVC coating (1.12 ± 0.12 μm) was lower than that (3.14 ± 1.93 μm) of Ca-P coating, suggesting the formation of refined Ca-P particles resulting from the VC addition. The corrosion resistance of the coated samples was characterized via electrochemical polarization, impedance spectroscopy, and immersion hydrogen evolution tests. The cell toxicity of the coated samples was evaluated utilizing mouse MC3T3-E1 pre-osteoblasts. The charge transfer resistance (Rct) of the Ca-PVC coated alloy increased as compared to the bare and Ca-P coated alloy samples. The Ca-PVC coated alloy exhibited minimal corrosion current density (1.36 × 10−6 A cm−2), which is one order of magnitude lower in comparison to that of the Ca-P coated alloy. These results confirm that VC addition greatly enhanced the coating resistance on AZ31 Mg alloy. It was also noticed that the Ca-PVC coated samples rapidly induced the formation of apatite after immersion in Hank's solution. VC was mainly transformed to L-Threonic acid, which facilitated the nucleation process of the Ca-PVC coating and significantly increased the thickness, density, and bonding strength of the coating. With enhanced corrosion resistance property and excellent biocompatibility, Ca-PVC coating has great potential for application in biodegradable Mg-based alloys.

BackgroundLong-term exposure to air pollution and physical activity (PA) are linked to blood pressure and hypertension. However, the joint effect of air pollution and PA on blood pressure and hypertension are still unknown in Chinese middle-aged and older adults.MethodsA total of 14,622 middle-aged and older adults from the China Health and Retirement Longitudinal Study wave 3 were included in this study. Ambient air pollution [particulate matter with diameter ≤ 2.5 μm (PM2.5), or ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO)] were estimated using satellite-based spatiotemporal models. PA was investigated using International Physical Activity Questionnaire. Generalized linear models were used to examine the associations of air pollution, PA score with blood pressure [systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP)], and the prevalence of hypertension. Subgroup analysis was conducted to investigate the effects of air pollution on blood pressure and the prevalence of hypertension in different PA groups.ResultsThe results showed that for each inter-quartile range (IQR) increase in PM2.5 (25.45 μg/m3), PM10 (40.56 μg/m3), SO2 (18.61 μg/m3), NO2 (11.16 μg/m3), CO (0.42 mg/m3) and PA score (161.3 MET/h-week), the adjusted odd ratio (OR) of hypertension was 1.207 (95% confidence interval (CI): 1.137, 1.281), 1.189 (95%CI: 1.122, 1.260), 1.186 (95%CI: 1.112, 1.266), 1.186 (95%CI: 1.116, 1.260), 1.288 (95%CI: 1.223, 1.357), 0.948 (95%CI: 0.899, 0.999), respectively. Long-term exposure to PM2.5, PM10, SO2, NO2, and CO was associated with increased SBP, DBP, and MAP levels. For example, each IQR increase in PM2.5 was associated with 1.20 mmHg (95%CI: 0.69, 1.72) change in SBP, 0.66 mmHg (95%CI: 0.36, 0.97) change in DBP, and 0.84 mmHg (95%CI: 0.49, 1.19) change in MAP levels, respectively. Each IQR increase in PA score was associated with −0.56 mmHg (95%CI: −1.03, −0.09) change in SBP, −0.32 mmHg (95%CI: −0.59, −0.05) change in DBP, and −0.33 mmHg (95%CI: −0.64, −0.02) change in MAP levels, respectively. Subgroup analysis found that the estimated effects in the sufficient PA group were lower than that in the insufficient PA group.ConclusionLong-term exposure to air pollutants is associated with increased blood pressure and hypertension risk, while high-level PA is associated with decreased blood pressure and hypertension risk. Strengthening PA might attenuate the adverse effects of air pollution on blood pressure and hypertension risk.

BackgroundCardiac arrhythmia is a common disease associated with high mortality and morbidity. Circulating leukocyte counts, which serve as a biomarker for assessing systemic immune status, have been linked to arrhythmias in observational studies. However, observational studies are plagued by confounding factors and reverse causality, whether alterations in circulating leukocyte components are causally associated with arrhythmias remains uncertain. The present study explored this question based on genetic evidence.Methods and findingsWe performed Mendelian randomization (MR) analysis to evaluate whether alterations in leukocyte counts affect aggregated risk of all types of arrhythmia or risk of five specific types of arrhythmia. Single-nucleotide polymorphisms serving as proxies for leukocyte differential counts were retrieved from the Blood Cell Consortium, and statistical data on arrhythmias were obtained from the UK Biobank), FinnGenand a meta-analysis of genome-wide association studies for atrial fibrillation. We applied inverse variance-weighted method as the primary analysis, complemented by a series of sensitivity analyses. Bidirectional analyses were conducted to assess reverse causality. Finally, multivariable MR was performed to study the joint effects of multiple risk factors. We found that genetically predicted differential leukocyte counts were not significantly associated with aggregated occurrence of all types of arrhythmia. In contrast, each 1-standard deviation increase in lymphocyte count was associated with 46% higher risk of atrioventricular block (OR 1.46, 95% CI 1.11–1.93, p=0.0065). A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy. Reverse MR analysis suggested that atrioventricular block was unlikely to cause changes in lymphocyte count. Primary MR analysis based on the inverse-variance weighted method suggested that changes in neutrophil count alter risk of right bundle branch block, and changes in basophil count alter risk of atrial fibrillation. However, these causal relationships were not robust in sensitivity analyses. We found no compelling evidence that neutrophil or lymphocyte counts cause atrial fibrillation.ConclusionOur data support higher lymphocyte count as a causal risk factor for atrioventricular block. These results highlight the importance of immune cells in the pathogenesis of specific cardiac conduction disorders.

Abstract Apparent treatment‐resistant hypertension (aTRH) is the most commonly used term to report resistant hypertension (RH) and is considered as a common problem in dialysis population. However, few reports have focused on peritoneal dialysis (PD) hypertensive patients. The authors conducted a multi‐center cross‐sectional study involving 1789 PD patients from nine centers in Guangdong, China. The prevalence of aTRH was estimated by home blood pressure (BP) monitoring. Evaluating drug adherence through Eight‐item Morisky Medication Adherence Scale (MMAS‐8) and pill counting was performed to assess RH in one PD center. Related factors of aTRH were analyzed using logistic regression analysis. The prevalence of aTRH in PD patients was estimated at 42.2% (755 out of 1789 hypertensive patients) based on home BP. Of those, 91.4% patients were classified as uncontrolled RH, 2.0% as controlled RH, and 6.6% as refractory hypertension. The prevalence of RH was 40.6% and 41.9% among those with medium/high adherence based on the MMAS‐8 scores and the pill counting rate, respectively. PD patients who were younger, with higher body mass index, with lower serum albumin and poorer dialysis adequacy were significantly associated with higher aTRH incident. In conclusion, the present study demonstrates a high prevalence of aTRH in PD population, which occurs in about two in five treated hypertensive patients. Nutritional status and dialysis adequacy might tightly associate with aTRH.