[Characteristics and Drivers of Soil Carbon, Nitrogen, and Phosphorus Ecological Stoichiometry at the Heavy Degradation Stage of the Alpine Meadow].

An in-depth understanding of the soil nutrient status and balance relationship can help the effective recovery and management of alpine degraded meadows. In order to study the balance relationship among soil carbon, nitrogen, and phosphorus nutrients during the heavy degradation stage of meadows, field sampling and investigation, indoor analysis, and mathematical statistics were used to explore the characteristics and driving factors of changes in soil carbon, nitrogen, and phosphorus content, storage, and ecological stoichiometry during the heavy degradation stage of alpine meadows in the Sanjiangyuan region. The results showed that in the heavy degradation stage, miscellaneous grass plants occupied absolute dominance, soil C∶N∶P was approximately 32.83∶3.87∶0.67, and there was certain nitrogen limitation. The coefficients of variation of soil carbon, nitrogen, and phosphorus content were in the following order： organic carbon （1.09） > total nitrogen （0.63） > total phosphorus （0.29）. The organic carbon content and the carbon and nitrogen ratio showed a significant linear decreasing trend with the increase in the grassland degradation index （GDI）, while the total phosphorus content and organic carbon storage showed a significant non-linear change, in which the total phosphorus content showed a significant gentle U-shaped distribution, and the organic carbon storage decreased more gently at the beginning of the heavy degradation stage and then decreased sharply when the GDI was 57.9. The results of Mantel correlation analysis showed that the soil carbon to nitrogen ratio, carbon to phosphorus ratio, and nitrogen to phosphorus ratio showed significant correlation with organic carbon content and storage and total nitrogen storage. The results of structural equation modeling indicated that soil water content had direct effects as well as indirect through vegetation factors, soil carbon, nitrogen, and phosphorus ecological stoichiometry ratios, and soil water content and vegetation factors （height, cover, and biomass） were key environmental factors affecting soil ecological stoichiometry. The research results can provide scientific basis and practical guidance for the restoration of heavily degraded grassland in alpine meadows.

MulCPred: Learning Multi-Modal Concepts for Explainable Pedestrian Action Prediction.

Pedestrian action prediction is crucial for many applications such as autonomous driving. However, state-of-the-art methods lack the explainability needed for trustworthy predictions. In this paper, a novel framework called MulCPred is proposed that explains its predictions based on multi-modal concepts represented by training samples. Previous concept-based methods have limitations, including the following: (1) they cannot be directly applied to multi-modal cases; (2) they lack the locality needed to attend to details in the inputs; (3) they are susceptible to mode collapse. These limitations are tackled accordingly through the following approaches: (1) a linear aggregator to integrate the activation results of the concepts into predictions, which associates concepts of different modalities and provides ante hoc explanations of the relevance between the concepts and the predictions; (2) a channel-wise recalibration module that attends to local spatiotemporal regions, which enables the concepts with locality; (3) a feature regularization loss that encourages the concepts to learn diverse patterns. MulCPred is evaluated on multiple datasets and tasks. Both qualitative and quantitative results demonstrate that MulCPred is promising in improving the explainability of pedestrian action prediction without obvious performance degradation. Moreover, by removing unrecognizable concepts, MulCPred shows improved cross-dataset prediction performance, suggesting its potential for further generalization.

Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader.

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) and other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders of CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery of ZLC491 as a potent, selective, and orally bioavailable CDK12/13 PROTAC degrader. The compound effectively degraded CDK12 and CDK13 with DC50 values of 32 and 28 nM, respectively, in TNBC MDA-MB-231 cells. Global proteomic assessment and mechanistic studies revealed that ZLC491 selectively induced CDK12/13 degradation in a cereblon- and proteasome-dependent manner. Furthermore, the molecule efficiently suppressed transcription and expression of long genes, predominantly a subset of genes associated with DNA damage response, and significantly inhibited proliferation of multiple TNBC cell lines. Importantly, ZLC491 achieved an oral bioavailability of 46.8% in rats and demonstrated potent in vivo degradative effects on CDK12/13 in an MDA-MB-231 xenografted mouse model.

Biomechanical comparison of Gofried positive support reduction of Pauwels type III femoral neck fractures: A finite elements analysis.

OBJECTIVE: This study aims to investigate the biomechanical characteristics of non-anatomical reduction and different screw positions on the stability of Pauwels type III femoral neck fractures. METHODS: Three-dimensional finite element models of femoral neck fractures were constructed using CT images. Four types of internal fixation methods were simulated, including biplane double-supported screw fixation (BDSF), three inverted triangular parallel cannulated screws (3CS), new parallel cannulated screws with posterior screws moving down (New 3CS), and two parallel cannulated screws (2CS). von Mises stress and total displacement were compared between the fracture models after the femoral head was subjected to an axial load of 2100 N. Stress and displacement data for the implants and the femur were recorded for each fixation method and compared. RESULTS: The results demonstrated that positive reduction of a Pauwels type III femoral neck fracture provided greater stability than neutral or negative reduction. Specifically, the BDSF group showed the lowest maximum von Mises stress in the femur (17.66 MPa) in positive reduction, compared to 3CS (21.08 MPa), New 3CS (22.14 MPa), and 2CS (36.57 MPa). The total displacement of positive reduction in the BDSF group was 0.3143 mm, which was lower than in the 3CS (0.3498 mm), New 3CS (0.3343 mm), and 2CS (0.4533 mm) groups. The stress distribution in the positive support reduction group was lower than that of the other groups, indicating better load distribution. Among the three-screw fixation methods, the New 3CS system exhibited the highest stress in the screws (with a peak of 28.62 MPa), while the 2CS group displayed the highest stresses overall, both in the femur and the screws. CONCLUSION: For Pauwels type III femoral neck fractures, a positive support reduction with BDSF fixation exhibited superior biomechanical performance than negative reduction. Based on the finite element analysis conducted in this study, the positive support reduction with BDSF fixation can enhance fixation stability, suggesting that non-anatomical reduction is recommended.

Emergency department discharges directly to hospice: Longitudinal assessment of a streamlined referral program.

INTRODUCTION: 80 % of Americans wish to die somewhere other than a hospital, and hospice is an essential resource for providing such care. The emergency department (ED) is an important location for identifying patients with end-of-life care needs and providing access to hospice. The objective of this study was to analyze a quality improvement (QI) program designed to increase the number of patients referred directly to hospice from the ED, without the need for an observation stay and without access to in-hospital hospice. METHODS: We implemented a QI program in September 2021 consisting of three components: (1) clarification and streamlining of referral workflows, (2) staff/provider education on hospice and workflows, and (3) electronic medical record (EMR) tools to facilitate hospice transitions. The primary outcome was the change in monthly ED-to-hospice cases pre- and post-implementation. We also calculated the monthly incidence rate of ED-to-hospice transfers. The secondary outcome was ED length of stay (LOS). RESULTS: 202 patients completed ED-to-hospice transfers from January 1, 2019 to February 29, 2024. 98 patients transitioned from the ED to hospice before QI implementation, and 104 patients transitioned after implementation. We observed a slight but insignificant increase in the mean monthly ED-to-hospice cases from 3.16 patients per month pre-implementation to 3.47 patients per month post-implementation (P = 0.46). We found no significant difference in the monthly incidence rate of ED-to-hospice cases before and after implementation (P = 0.78). ED LOS was unaffected (P = 0.21). CONCLUSION: In this largest study to date on direct ED-to-hospice discharges, a QI program focused on workflow optimization, education, and EMR modification was insufficient to significantly impact ED-to-hospice discharges. Future efforts to increase hospice transitions from the ED should investigate methods to improve patient identification, the impact of in-hospital hospice programs, and coordination with hospital and community teams to support home-based care for those desiring to remain there.

Relationship between serum uric acid levels and periodontitis-A cross-sectional study.

OBJECTIVES: Whether there is an association between serum uric acid level (sUA) and periodontitis remains unclear. The aim of this study was to investigate the association between moderate/severe periodontitis and sUA in US adults. MATERIALS AND METHODS: A total of 3398 participants were included in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. The independent variable was sUA and the dependent variable was periodontitis. SUA for continuous variables, periodontitis as classification variables. Covariate including social demographic variables, life style, systemic diseases, etc. Multiple linear regression models were used to investigate the distribution of differences in covariates between different independent groups. To investigate the association between serum uric acid levels and moderate/severe periodontitis, three models were used (Model 1: unadjusted model; Model 2: adjusted for age, sex, and race/ethnicity; Model 3: adjusted for age, sex, race/ethnicity, education, household income/poverty ratio, smoking behavior, alcohol consumption, dental floss frequency, obesity, hypertension, diabetes, high cholesterol, hyperlipidemia, and sleep disorders). RESULTS: Among the 3398 patients, 42.5% had moderate/severe periodontitis. Multivariate logistic regression analysis showed that sUA was significantly associated with moderate/severe periodontitis (OR = 1.10, 95%CI: (1.03, 1.16), P = 0.0020) after adjusting for potential confounding factors. In addition, it may vary by race/ethnicity and gender. The association between sUA levels and the prevalence ofperiodontitis was U-shaped in women and non-Hispanic blacks. CONCLUSION: sUA level is associated with moderate to severe periodontitis. However, the association between sUA levels and the occurrence of periodontitis in women and non-Hispanic blacks followed a U-shaped curve. CLINICAL RELEVANCE: sUA may directly or indirectly contribute to the global burden of periodontal disease, but there is little evidence that sUA is directly related to periodontitis.This study further supports that high uric acid levels are closely related to periodontitis and may contribute to the control of periodontitis. It also provides new insights into whether it can be used as an indicator to assess the risk or progression of periodontitis. More studies are needed to confirm the relationship between sUA and periodontitis.

Neuronal LAMP2A-mediated reduction of adenylyl cyclases induces acute neurodegenerative responses and neuroinflammation after ischemic stroke.

Lysosomes regulate cellular metabolism to maintain cell survival, but the mechanisms whereby they determine neuronal cell fate after acute metabolic stress are unknown. Neuron-enriched lysosomal membrane protein LAMP2A is involved in selective chaperone-mediated autophagy and exosome loading. This study demonstrates that abnormalities in the neuronal LAMP2A-lysosomal pathway cause neurological deficits following ischemic stroke and that this is an early inducer of the PANoptosis-like molecular pathway and neuroinflammation, simultaneously inducing upregulation of FADD, RIPK3, and MLKL after ischemia. Quantitative proteomic and pharmacological analysis showed that after acute metabolic stress, the neuronal LAMP2A pathway induced acute synaptic degeneration and PANoptosis-like responses involving downregulation of protein kinase A (PKA) signaling. LAMP2A directed post-stroke lysosomal degradation of adenylyl cyclases (ADCY), including ADCY1 and ADCY3 in cortical neurons. Post-stroke treatment with cAMP mimetic or ADCY activator salvaged cortical neurons from PANoptosis-like responses and neuroinflammation, suggesting that the neuronal ADCY-cAMP-PKA axis is an upstream arrester of the pathophysiological process following an ischemic stroke. This study demonstrates that the neuronal LAMP2A-lysosmal pathway drives intricate acute neurodegenerative and neuroinflammatory responses after brain metabolic stress by downregulating the ADCY-PKA signaling cascade, and highlights the therapeutic potential of PKA signal inducers for improving stroke outcomes.

LIG1 is a novel marker for bladder cancer prognosis: evidence based on experimental studies, machine learning and single-cell sequencing.

Background: Bladder cancer, a highly fatal disease, poses a significant threat to patients. Positioned at 19q13.2-13.3, LIG1, one of the four DNA ligases in mammalian cells, is frequently deleted in tumour cells of diverse origins. Despite this, the precise involvement of LIG1 in BLCA remains elusive. This pioneering investigation delves into the uncharted territory of LIG1's impact on BLCA. Our primary objective is to elucidate the intricate interplay between LIG1 and BLCA, alongside exploring its correlation with various clinicopathological factors. Methods: We retrieved gene expression data of para-carcinoma tissues and bladder cancer (BLCA) from the GEO repository. Single-cell sequencing data were processed using the "Seurat" package. Differential expression analysis was then performed with the "Limma" package. The construction of scale-free gene co-expression networks was achieved using the "WGCNA" package. Subsequently, a Venn diagram was utilized to extract genes from the positively correlated modules identified by WGCNA and intersect them with differentially expressed genes (DEGs), isolating the overlapping genes. The "STRINGdb" package was employed to establish the protein-protein interaction (PPI) network.Hub genes were identified through the PPI network using the Betweenness Centrality (BC) algorithm. We conducted KEGG and GO enrichment analyses to uncover the regulatory mechanisms and biological functions associated with the hub genes. A machine-learning diagnostic model was established using the R package "mlr3verse." Mutation profiles between the LIG1^high and LIG1^low groups were visualized using the BEST website. Survival analyses within the LIG1^high and LIG1^low groups were performed using the BEST website and the GENT2 website. Finally, a series of functional experiments were executed to validate the functional role of LIG1 in BLCA. Results: Our investigation revealed an upregulation of LIG1 in BLCA specimens, with heightened LIG1 levels correlating with unfavorable overall survival outcomes. Functional enrichment analysis of hub genes, as evidenced by GO and KEGG enrichment analyses, highlighted LIG1's involvement in critical function such as the DNA replication, cellular senescence, cell cycle and the p53 signalling pathway. Notably, the mutational landscape of BLCA varied significantly between LIG1high and LIG1low groups.Immune infiltrating analyses suggested a pivotal role for LIG1 in immune cell recruitment and immune regulation within the BLCA microenvironment, thereby impacting prognosis. Subsequent experimental validations further underscored the significance of LIG1 in BLCA pathogenesis, consolidating its functional relevance in BLCA samples. Conclusions: Our research demonstrates that LIG1 plays a crucial role in promoting bladder cancer malignant progression by heightening proliferation, invasion, EMT, and other key functions, thereby serving as a potential risk biomarker.

Measuring total hip arthroplasty liner wear using the EOS Imaging System: experimental and clinical results.

BACKGROUND AND PURPOSE: The low-dose EOS Imaging System is an emerging tool for 3-dimensional measurements in orthopedics. The clinical feasibility for measuring total hip arthroplasty (THA) liner wear has not yet been investigated. We aimed to evaluate the feasibility of using EOS to measure THA liner wear by examining the experimental accuracy using a THA phantom and clinical precision of patients with THA, considering a clinically relevant precision at the 95% repeatability limit to be 0.2 mm. METHODS: An experimental THA phantom with movable stem and a fixed cup with a plastic liner was constructed to simulate progressive 3D liner wear. Series of 11 pairs of radiographs with 50 µm femoral movement in between were obtained for each 3D axis in EOS. 30 patients with a THA were scanned twice using EOS to assess precision. Model-based radiostereometric analysis (RSA) was used for wear measurement. RESULTS: The mean difference (true minus simulated wear) with standard deviation (SD) and 95% limits of agreement for experimental THA wear were 0.005 (0.037) and [-0.069 to 0.079] mm for the vertical (y) axis. The mean (SD) and 95% repeatability limit for precision for clinical measurement were -0.029 (0.105) and 0.218 mm. CONCLUSION: Experimental THA liner wear using EOS was within clinically relevant tolerances and without bias. The clinical precision was just outside our defined clinically relevant precision. Compared with conventional RSA, EOS is less accurate and precise but may still be of value for certain clinical applications, provided larger sample size or longer follow-up are available.

Single nucleotide polymorphisms in the development of osteomyelitis and prosthetic joint infection: a narrative review.

Currently, despite advancements in diagnostic and therapeutic modalities, osteomyelitis and prosthetic joint infection (PJI) continue to pose significant challenges for orthopaedic surgeons. These challenges are primarily attributed to the high degree of heterogeneity exhibited by these disorders, which are influenced by a combination of environmental and host factors. Recent research efforts have delved into the pathogenesis of osteomyelitis and PJI by investigating single nucleotide polymorphisms (SNPs). This review comprehensively summarizes the current evidence regarding the associations between SNPs and the predisposition to osteomyelitis and PJI across diverse populations. The findings suggest potential linkages between SNPs in genes such as IL-1, IL-6, IFN-γ, TNF-α, VDR, tPA, CTSG, COX-2, MMP1, SLC11A1, Bax, NOS2, and NLRP3 with the development of osteomyelitis. Furthermore, SNPs in genes like IL-1, IL-6, TNF-α, MBL, OPG, RANK, and GCSFR are implicated in susceptibility to PJI. However, it is noted that most of these studies are single-center reports, lacking in-depth mechanistic research. To gain a more profound understanding of the roles played by various SNPs in the development of osteomyelitis and PJI, future multi-center studies and fundamental investigations are deemed necessary.

Effect of preoperative autologous platelet-rich plasmapheresis on postoperative bleeding in patients undergoing heart valve surgery.

Background: Cardiovascular surgeries often require deep hypothermic circulatory arrest and cardiopulmonary bypass (CPB), which can disrupt blood clotting and lead to excessive bleeding. Traditional treatments involve transfusing blood and blood products, which can have adverse effects and place significant strain on the global blood supply. Research suggests that autologous platelet-rich plasmapheresis (aPRP) may reduce the need for transfusions by preserving blood components. However, the impact of aPRP on postoperative blood loss and clinical outcomes in cardiovascular surgery remains controversial. This study aimed to examine the effects of aPRP on postoperative blood loss and recovery in patients undergoing heart valve surgery. Methods: A total of 183 patients were divided into either aPRP or control groups. The aPRP group received aPRP before CPB, whereas the control group did not. The primary endpoint was postoperative bleeding between the groups. The secondary endpoints were postoperative bleeding risk factors and clinical outcome assessment. Logistic regression analysis with covariate adjustment was used to calculate these risk factors. Results: A total of 76 patients (41.5%) in the aPRP group and 107 patients (58.5%) in the control group were included in the analysis. No significant difference was found in the occurrence of postoperative bleeding [odds ratio (OR) =0.53, 95% confidence interval (CI): 0.28-1.00, P=0.05], and the aPRP group had fewer complications than the controls (OR =0.28, 95% CI: 0.10-0.68, P=0.009). However, after adjusting for the New York Heart Association (NYHA) classification, diabetes, arrhythmology, mean activated clotting time (ACTmean), CPB, bleeding, thoracotomy, and body mass index (BMI), there was a significant difference in postoperative bleeding (adjusted OR =0.47, 95% CI: 0.22-0.98, P=0.04) and complications (adjusted OR =0.23, 95% CI: 0.07-0.64, P=0.008) between the two groups. Conclusions: Preoperative aPRP can improve postoperative outcomes and reduce complications in patients undergoing heart valve surgery.

Molecular Dynamics Investigation of Metastable Structure and Hybridization Bond Evolution in High-Entropy CoCrFeNi Heterostructured Amorphous Carbon Films.

Heterogeneous element doping in amorphous carbon films can reduce residual stresses and improve plastic deformation. Nevertheless, the effects of dopant content and size on the metastable transition mechanism between sp2-C and sp3-C atoms during the deformation process are unclear and difficult to be in situ observed and researched, experimentally. In this work, the mechanical properties and the structural evolution during the nanoindentation of amorphous CoCrFeNi sphere-doped carbon heterostructured films with different radii were simulated. The results indicate that the hardness H and elastic modulus E of the films decreased with the increase of the dopant addition. H decreases from 50.69 to 28.94 GPa, and E decreases from 664.39 to 448.62 GPa. The decrease in the elastic recovery and the enlargement of the shear transition zones indicate that the presence of the amorphous CoCrFeNi dopant can significantly improve the plastic deformation capacity of the films. During the nanoindentation process, the spherical dopants reduce the stress and shear strain of the regions under the indenter in a-C films. The reduction of compressive and shear stresses in the film can inhibit the C atom metastable transition from sp2-C to sp3-C. This can provide a theoretical basis for the development and design of heavy-load and high-deformation-rate a-C films.

[Spectral Characteristics of Dissolved Organic Matter in Sediments from Yuanhe River Basin].

Dissolved organic matter （DOM） plays an important role in indicating the pollution of the water environment, and sediment is the main source of endogenous pollution of the water environment. Research on the spectral characteristics of DOM in sediments was important for the interpretation of water environment pollution. In this study, UV-visible absorption spectroscopy and three-dimensional fluorescence spectroscopy combined with the parallel factor analysis （PARAFAC） were used to analyze the fluorescent components, sources, and influencing factors of DOM in sediments from the Yuanhe River Basin. The results showed that the average of ω（TN）, ω（TP）, and ω（OM） in sediments from the Yuanhe River Basin were 0.52, 0.66, and 21.22 g·kg-1, respectively. The concentrations of total nitrogen and total phosphorus increased along the flow direction. In addition, the sediment DOM from the Yuanhe River Basin mainly originated from terrestrial sources. The chromophoric DOM concentration and aromaticity of DOM from the downstream reaches were significantly higher than those from the upstream and midstream reaches. Based on PARAFAC, four fluorescent components of DOM in sediments from the Yuanhe River Basin were identified, including three humus-like components （C1, C3, and C4） and one protein-like component （C2）. The sediment DOM was dominated by humus-like materials. Moreover, the fluorescent intensity of the fluorescent components was higher in the downstream reaches. Redundancy analysis revealed that the physicochemical properties of sediments in the mainstream and downstream reaches played a more significant role in the spectral properties of DOM. Phosphorus pollution and the terrestrial humus-like substance of sediment DOM were homologous. These results indicated that the spectral properties of DOM were the indicator of water environmental pollution in the region with strong anthropogenic influence.

Folylpolyglutamate synthetase inactivation in relapsed ALL induces a druggable folate metabolic vulnerability.

AIMS: The antifolate methotrexate (MTX) is an anchor drug used in acute lymphoblastic leukemia (ALL) with poorly understood chemoresistance mechanisms in relapse. Herein we find decreased folate polyglutamylation network activities and inactivating FPGS mutations, both of which could induce MTX resistance and folate metabolic vulnerability in relapsed ALL. METHODS: We utilized integrated systems biology analysis of transcriptomic and genomic data from relapse ALL cohorts to infer hidden ALL relapse drivers and related genetic alternations during clonal evolution. The drug sensitivity assay was used to determine the impact of relapse-specific FPGS mutations on sensitivity to different antifolates and chemotherapeutics in ALL cells. We used liquid chromatography-mass spectrometry (LC-MS) to quantify MTX and folate polyglutamate levels in folylpoly-γ-glutamate synthetase (FPGS) mutant ALL cells. Enzymatic activity and protein degradation assays were also conducted to characterize the catalytic properties and protein stabilities of FPGS mutants. An ALL cell line-derived mouse leukemia xenograft model was used to evaluate the in vivo impact of FPGS inactivation on leukemogenesis and sensitivity to the polyglutamatable antifolate MTX as well as non-polyglutamatble lipophilic antifolate trimetrexate (TMQ). RESULTS: We found a significant decrease in folate polyglutamylation network activities during ALL relapse using RNA-seq data. Supported by functional evidence, we identified multifactorial mechanisms of FPGS inactivation in relapsed ALL, including its decreased network activity and gene expression, focal gene deletion, impaired catalytic activity, and increased protein degradation. These deleterious FPGS alterations induce MTX resistance and inevitably cause marked intracellular folate shrinkage, which could be efficiently targeted by a polyglutamylation-independent lipophilic antifolate TMQ in vitro and in vivo. CONCLUSIONS: MTX resistance in relapsed ALL relies on FPGS inactivation, which inevitably induces a folate metabolic vulnerability, allowing for an efficacious antifolate ALL treatment strategy that is based upon TMQ, thereby surmounting chemoresistance in relapsed ALL.

[Interaction Effects of Vegetation and Soil Factors on Microbial Communities in Alpine Steppe Under Degradation].

To clarify the regulating effect of vegetation and soil factors on microbial communities in the alpine steppe under degradation on the Qinghai-Xizang Plateau, the alpine steppe in the Sanjiangyuan area of the Qinghai-Tibet Plateau was chosen. We analyzed the differences in vegetation and soil factors in different stages of degradation （non-degradation, moderate degradation, and severe degradation） and detected the variations in microbial community characteristics in the alpine steppe under different degradation stages using high-throughput sequencing technology. Eventually, redundancy analysis （RDA） and multiple regression matrixes （MRM） based on the similarity or dissimilarity matrix were used to identify key environmental factors regulating microbial （bacterial and fungal） community changes under degradation. The results showed that the degradation of the alpine steppe significantly changed the community coverage, height, biomass, and important value of graminae； significantly reduced the contents of soil organic matter, total nitrogen, total phosphorus, and silt； and increased the soil bulk density and sand content. Degradation did not change the composition of bacteria and fungi, but their composition proportions changed and also resulted in the loss of microbial richness （Chao1 index and Richness index） but did not significantly change the microbial diversity （Shannon index）. With the occurrence of degradation, the vegetation characteristics, soil physicochemical properties, and microbial diversity showed a consistent change trend. Combined with the characteristics of the network topology changes （the number of nodes and clustering coefficient significantly decreased）, it was found that degradation of the alpine steppe led to the decline of interspecies interactions, decentralization of network, and homogenization of microorganisms, but the cooperation relations among the species were maintained （positive correlation connections accounted for more than 90% in all degradation stages）. Under the alpine steppe degradation, the vegetation-soil interaction had the greatest effect on soil bacterial community, whereas soil physicochemical properties had the greatest influence on soil fungal community. Specifically, vegetation community height, biomass, and soil bulk density were the mutual factors regulating soil microorganisms, whereas the vegetation Simpson index, important value of graminae, soil total phosphorus, total potassium, and silt content were the unique factors affecting the soil bacterial community, and soil pH and total nitrogen content were the particular factors affecting the soil fungal community.

Dietary effects of vitamin C on antioxidant capacity, intestinal microbiota and the resistance of pathogenic bacteria in cultured Silver pomfret (Pampus argenteus).

As most teleosts are unable to synthesize vitamin C, supplemental diets containing vitamin C diets play a crucial role in fish health. The aim of this study was to investigate the effect of dietary vitamin C on the intestinal enzyme activity and intestinal microbiota of silver pomfre (Pampus argenteus). Four experimental diets were supplemented with basic diets containing 300 mg of vitamin C/kg (group tjl3), 600 mg of vitamin C/kg (group tjl6), and 1200 mg of vitamin C/kg (group tjl12), as well as vitamin C-free supplemental basic diet (group tjl0), respectively. The four diets were fed to juvenile P. argenteus (average initial weight: 4.68 ± 0.93 g) for 6 weeks. The results showed that the activity of SOD (superoxide dismutase) and CAT (catalase) increased significantly while that of MDA (malondialdehyde) decreased significantly in group tjl3 compared to vitamin group tjl0. At the genus level, groups tjl0, tjl6, and tjl12 contained the same dominant microbial community, Stenotrophomonas, Photobacterium, and Vibrio, whereas group tjl3 was dominated by Stenotrophomonas, Delftia, and Bacteroides. Among the fish fed with a basic diet containing 300 mg of vitamin C/kg, the intestines exhibited a notable abundance of probiotic bacteria, including lactic acid bacteria (Lactobacillus) and Bacillus. The abundance of Aeromonas in groups tjl3 and tjl6 was lower than that of the vitamin C-free supplemental basic diet group, whereas Aeromonas was not detected in group tjl12. In addition, a causative agent of the disease outbreak in cultured P. argenteus, Photobacterium damselae subsp. Damselae (PDD) was the dominant microbiota community in groups tjl0, tjl6 and tjl12, whereas the abundance of PDD in group tjl3 was the lowest among the diets. Taken together, the diets supplied with vitamin C could influence the composition microbial community of P. argenteus. The low level of vitamin C (300 mg of vitamin C/kg per basic diet) supplementation could not only improve the antioxidant capacity but also resist the invasion of pathogenic bacteria.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

An Energy Efficient and Temperature Stable Digital FLL-based Wakeup Timer with Time-Domain Temperature Compensation.

This brief presents an on-chip digital intensive frequency-locked loop (DFLL)-based wakeup timer with a time-domain temperature compensation featuring a embedded temperature sensor. The proposed compensation exploits the deterministic temperature characteristics of two complementary resistors to stabilize the timer's operating frequency across the temperature by modulating the activation time window of the two resistors. As a result, it achieves a fine trimming step (± 1 ppm), allowing a small frequency error after trimming (<± 20 ppm). By reusing the DFLL structure, instead of employing a dedicated sensor, the temperature sensing operates in the background with negligible power (2 %) and hardware overhead (< 1 %). The chip is fabricated in 40 nm CMOS, resulting in 0.9 pJ/cycle energy efficiency while achieving 8 ppm/ºC from -40ºC to 80ºC.

Effects of secondary cross-linking on the physicochemical properties of sodium alginate-hydrogel and in vitro release of anthocyanins.

To enhance the physicochemical properties and extend the release duration of sodium alginate (SA) hydrogels, this study explored the impact of acidifier type and the number of cross-linking on the physicochemical characteristics and in vitro anthocyanin release from SA hydrogels, utilizing calcium carbonate as the cross-linking agent. The findings revealed that the utilization of gluconolactone (GDL) as an acidifying agent in the preparation of SA hydrogels, as opposed to hydrochloric acid, resulted in a deceleration of the hydrolysis process of calcium carbonate. This deceleration led to the strengthening of hydrogen-bonding interactions and the development of a more compact network structure within the SA hydrogels. Consequently, there was a noticeable enhancement in the hardness, relaxation time, and anthocyanin encapsulation efficiency of the gels. Additionally, the release of anthocyanins in simulated intestinal fluid was delayed. Secondary cross-linking was found to facilitate ionic interactions between SA and Ca2+, further intensifying the denseness of the network structure and enhancing the physicochemical characteristics of the SA hydrogels. Overall, SA hydrogels processed with GDL as the acidifier and subjected to secondary cross-linking exhibited improved physicochemical properties, delayed release effects, and proved to be an efficient system for the delayed release of anthocyanins.

Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.