New look at the power of zero coronary artery calcium (CAC) in Asian population: a systemic review and meta-analysis.

Background: Numerous studies have validated a 5-year warranty period for heart health in Western populations with a coronary artery calcium (CAC) score of zero. While the calcium score is a crucial cardiovascular risk indicator, its interpretation in Asian populations remains unclear. This meta-analysis aimed to clarify the uncertainty surrounding the prevalence, warranty period, and prognostic implications of zero CAC scores in Asian populations. It also examined the impact of sex on subclinical CAC progression. While the calcium score is a crucial cardiovascular risk indicator, its interpretation in Asian populations remains unclear. The study aimed to shed light on these issues by exploring the specificities of subclinical CAC progression in the Asian context. Methods: Our systematic literature search, from the study's inception to October 2023, targeted studies on subclinical CAC progression in the Asian population with a zero CAC score. We searched the Cochrane Library, and PubMed. The search terms included "zero score", "coronary calcification", "zero CAC score", and "CAC scan". Results: We evaluated seven published studies through a meta-analysis and assessed the risk of bias using the Newcastle-Ottawa Scale (NOS). In this meta-analysis of three observational studies addressing zero CAC prevalence (n=7,661), the pooled prevalence of zero CAC scores in the Asian population was 18.2% [95% confidence interval (CI): 12.5-25.9%]. A significant difference in follow-up warranty period was observed between the CAC zero group and subclinical CAC progression group (mean difference, 1.26 years; 95% CI: 0.94-1.58; P<0.001). Furthermore, the conversion rate of subclinical CAC progression differed significantly between males and females (risk ratio, 2.37; 95% CI: 1.98-2.84; P<0.001). Analysis of four studies revealed a notable discrepancy in the major adverse cardiovascular event (MACE) rate between the CAC (-) and CAC (+) groups (risk ratio, 4.78; 95% CI: 2.21-10.36; P<0.001). Conclusions: The meta-analysis of zero CAC scores in Asian populations suggested an 18.2% prevalence. A 5-year warranty period was noted, with heightened subclinical CAC progression likelihood after this duration. Additionally, sex-based differences were observed in subclinical CAC progression rates. These findings will provide clinical cardiovascular risk stratification for guiding gender-specific clinical decision-making in asymptomatic in Asian individuals.

Species pool and soil properties in mangrove habitats influence the species-immigration process of diazotrophic communities across southern China.

Microbial immigration is an ecological process in natural environments; however, the ecological trade-off mechanisms that govern the balance between species extinction and migration are still lacking. In this study, we investigated the mechanisms underlying the migration of diazotrophic communities from soil to leaves across six natural mangrove habitats in southern China. The results showed that the diazotrophic alpha and beta diversity exhibited significant regional and locational variations. The diazotrophic species pool gradually increased from the leaves to nonrhizosphere soil at each site, exhibiting a vertical distribution pattern. Mantel test analyses suggested that climate factors, particularly mean annual temperature, significantly influenced the structure of the diazotrophic community. The diazotrophic community assembly was mainly governed by dispersal limitation in soil and root samples, whereas dispersal limitation and ecological drift were dominant in leaves. Partial least squares path modeling revealed that the species pool and soil properties, particularly the oxidation-reduction potential and pH, were closely linked to the species-immigration ratio of diazotrophic communities. Our study provides novel insights for understanding the ecological trait diversity patterns and spread pathways of functional microbial communities between below- and aboveground habitats in natural ecosystems.IMPORTANCEEnvironmental selection plays key roles in microbial transmission. In this study, we have provided a comprehensive framework to elucidate the driving patterns of the ecological trade-offs in diazotrophic communities across large-scale mangrove habitats. Our research revealed that Bradyrhizobium japonicum, Marinobacterium lutimaris, and Agrobacterium tumefaciens were more abundant in root-associated soil than in leaves by internal and external pathways. The nonrhizospheric and rhizospheric soil samples harbored the most core amplicon sequence variants, indicating that these dominant diazotrophs could adapt to broader ecological niches. Correlation analysis indicated that the diversities of the diazotrophic community were regulated by biotic and abiotic factors. Furthermore, this study found a lower species immigration ratio in the soil than in the leaves. Both species pool and soil properties regulate the species-immigration mechanisms of the diazotrophic community. These results suggest that substantial species immigration is a widespread ecological process, leading to alterations in local community diversity across diverse host environments.

Interpretable Machine Learning Models Based on SHapley Additive exPlanations for Predicting the Risk of Cerebrospinal Fluid Leakage in Lumbar Fusion Surgery.

STUDY DESIGN: Retrospective study. OBJECTIVES: The objective of this investigation was to formulate and internally verify a customized machine learning (ML) framework for forecasting cerebrospinal fluid leakage (CSFL) in lumbar fusion surgery. This was accomplished by integrating imaging parameters and employing the SHapley Additive exPlanation (SHAP) technique to elucidate the interpretability of the model. SUMMARY OF BACKGROUND DATA: Given the increasing incidence and surgical volume of spinal degeneration worldwide, accurate predictions of postoperative complications are urgently needed. SHAP-based interpretable ML models have not been used for CSFL risk factor analysis in lumbar fusion surgery. METHODS: Clinical and imaging data were retrospectively collected from 3505 patients who underwent lumbar fusion surgery. Six distinct machine learning models were formulated: extreme gradient boosting (XGBoost), decision tree (DT), random forest (RF), support vector machine (SVM), Gaussian naive Bayes (GaussianNB), and K-nearest neighbors (KNN) models. Evaluation of model performance on the test dataset was performed using performance metrics, and the analysis was executed through the SHAP framework. RESULTS: CSFL was detected in 95 out of 3505 patients (2.71%). Notably, the XGBoost model exhibited outstanding accuracy in forecasting CSFLs, with high precision (0.9815), recall (0.6667), accuracy (0.8182), F1 score (0.7347), and AUC (0.7343). Additionally, through SHAP analysis, significant predictors of CSFL were identified, including ligamentum flavum thickness, zygapophysial joint degeneration grade, central spinal stenosis grade, decompression segment count, decompression mode, intervertebral height difference, Cobb angle, intervertebral height index difference, operation mode, lumbar segment lordosis angle difference, Meyerding grade of lumbar spondylolisthesis, and revision surgery. CONCLUSION: The combination of the XGBoost model with the SHAP is an effective tool for predicting the risk of CSFL during lumbar fusion surgery. Its implementation could aid clinicians in making informed decisions, potentially enhancing patient outcomes and lowering healthcare expenses. This study advocates for the adoption of this approach in clinical settings to enhance the evaluation of CSFL risk among patients undergoing lumbar fusion.

Designing Symmetric Gradient Honeycomb Structures with Carbon-Coated Iron-Based Composites for High-Efficiency Microwave Absorption.

The impedance matching of absorbers is a vital factor affecting their microwave absorption (MA) properties. In this work, we controllably synthesized Material of Institute Lavoisier 88C (MIL-88C) with varying aspect ratios (AR) as a precursor by regulating oil bath conditions, followed by one-step thermal decomposition to obtain carbon-coated iron-based composites. Modifying the precursor MIL-88C (Fe) preparation conditions, such as the molar ratio between metal ions and organic ligands (M/O), oil bath temperature, and oil bath time, influenced the phases, graphitization degree, and AR of the derivatives, enabling low filler loading, achieving well-matched impedance, and ensuring outstanding MA properties. The MOF-derivatives 2 (MD2)/polyvinylidene Difluoride (PVDF), MD3/PVDF, and MD4/PVDF absorbers all exhibited excellent MA properties with optimal filler loadings below 20 wt% and as low as 5 wt%. The MD2/PVDF (5 wt%) achieved a maximum effective absorption bandwidth (EAB) of 5.52 GHz (1.90 mm). The MD3/PVDF (10 wt%) possessed a minimum reflection loss (RLmin) value of - 67.4 at 12.56 GHz (2.13 mm). A symmetric gradient honeycomb structure (SGHS) was constructed utilizing the high-frequency structure simulator (HFSS) to further extend the EAB, achieving an EAB of 14.6 GHz and a RLmin of - 59.0 dB. This research offers a viable inspiration to creating structures or materials with high-efficiency MA properties.

Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China.

OBJECTIVES: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

Utility of an Externalized Temporary Transvenous Implantable Cardioverter-defibrillator System in the Setting of Ventricular Tachycardia Storm and Concurrent Device Infection Requiring Extraction.

With the expanding use of cardiac implantable electronic device (CIED) therapy, intravascular device infections are becoming more common. In the case of transvenous implantable cardioverter-defibrillator (ICD) infections requiring extraction for bacterial clearance, there remains no standard method to deliver temporary ICD therapy following device removal. We present a case of persistent bacteremia complicated by monomorphic ventricular tachycardia (VT) electrical storm where biventricular ICD system extraction was performed and a temporary transvenous dual-coil lead with an externalized ICD generator was used to treat VT episodes prior to the re-implantation of a new permanent system. This case demonstrates the utility of a temporary externalized transvenous ICD system in the successful detection and pace-termination of VT, thereby reducing episodes of painful and potentially harmful external defibrillator shocks during the treatment of CIED infection.

Multiply robust estimation of marginal structural models in observational studies subject to covariate-driven observations.

Electronic health records and other sources of observational data are increasingly used for drawing causal inferences. The estimation of a causal effect using these data not meant for research purposes is subject to confounding and irregularly-spaced covariate-driven observation times affecting the inference. A doubly-weighted estimator accounting for these features has previously been proposed that relies on the correct specification of two nuisance models used for the weights. In this work, we propose a novel consistent multiply robust estimator and demonstrate analytically and in comprehensive simulation studies that it is more flexible and more efficient than the only alternative estimator proposed for the same setting. It is further applied to data from the Add Health study in the United States to estimate the causal effect of therapy counseling on alcohol consumption in American adolescents.

Scalable Hypothalamic Arcuate Neuron Differentiation from Human Pluripotent Stem Cells Suitable for Modeling Metabolic and Reproductive Disorders.

The hypothalamus, composed of several nuclei, is essential for maintaining our body's homeostasis. The arcuate nucleus (ARC), located in the mediobasal hypothalamus, contains neuronal populations with eminent roles in energy and glucose homeostasis as well as reproduction. These neuronal populations are of great interest for translational research. To fulfill this promise, we used a robotic cell culture platform to provide a scalable and chemically defined approach for differentiating human pluripotent stem cells (hPSCs) into pro-opiomelanocortin (POMC), somatostatin (SST), tyrosine hydroxylase (TH) and gonadotropin-releasing hormone (GnRH) neuronal subpopulations with an ARC-like signature. This robust approach is reproducible across several distinct hPSC lines and exhibits a stepwise induction of key ventral diencephalon and ARC markers in transcriptomic profiling experiments. This is further corroborated by direct comparison to human fetal hypothalamus, and the enriched expression of genes implicated in obesity and type 2 diabetes (T2D). Genome-wide chromatin accessibility profiling by ATAC-seq identified accessible regulatory regions that can be utilized to predict candidate enhancers related to metabolic disorders and hypothalamic development. In depth molecular, cellular, and functional experiments unveiled the responsiveness of the hPSC-derived hypothalamic neurons to hormonal stimuli, such as insulin, neuropeptides including kisspeptin, and incretin mimetic drugs such as Exendin-4, highlighting their potential utility as physiologically relevant cellular models for disease studies. In addition, differential glucose and insulin treatments uncovered adaptability within the generated ARC neurons in the dynamic regulation of POMC and insulin receptors. In summary, the establishment of this model represents a novel, chemically defined, and scalable platform for manufacturing large numbers of hypothalamic arcuate neurons and serves as a valuable resource for modeling metabolic and reproductive disorders.

Risk Factors of Failed Conservative Treatment for Adjacent Vertebral Fractures Following Percutaneous Vertebroplasty.

STUDY DESIGN: A retrospective, single-center, observational study. OBJECTIVE: This study investigated the risk factors associated with the failure of conservative treatment for adjacent vertebral fractures (AVFs). SUMMARY OF BACKGROUND DATA: Adjacent vertebral fractures following vertebroplasty for osteoporotic vertebral compression fractures are not uncommon. Presently, there is a lack of consensus regarding the management of adjacent vertebral fractures. METHODS: We included patients who developed adjacent vertebral fractures within two years post single-level vertebroplasty between January 2013 and December 2020. All patients initially underwent six weeks of conservative treatment, including pain medications, bracing, and physical therapy. Surgical intervention was offered to those with intractable back pain due to AVFs. Baseline demographics, AVF characteristics, and radiological measurements were systematically collected, and sequential univariable and multivariable logistic regression analyses were conducted to explore the risk factors. RESULTS: Of the 114 patients with a mean age of 78.6 years, two-thirds (76 patients) tolerated conservative treatment well, while 38 required surgical interventions for adjacent vertebral fractures. Both groups demonstrated similar baseline demographics and radiological parameters regarding AVFs (P>0.05). The multivariable logistic regression analyses revealed that the development of AVFs later than six months post-vertebroplasty and their caudal location to the index vertebroplasty were the independent risk factors of unsuccessful conservative treatment, with odds ratios of 3.57 (95% confidence interval [CI]: 1.14-11.1, P=0.029) and 2.50 (95% CI: 1.09-5.88, P=0.032), respectively. CONCLUSION: Adjacent vertebral fractures following percutaneous vertebroplasty generally have favorable outcomes under conservative treatment. However, the timing and the relative anatomical location of adjacent vertebral fractures are associated with treatment efficacy. Adjacent vertebral fractures occurring later than six months following the initial vertebroplasty or situated in the caudal location to the index vertebroplasty may exhibit reduced responsiveness to conservative treatment. These patients might benefit from a more aggressive therapeutic approach. LEVEL OF EVIDENCE: 3.

Review of the Interfacial Structure and Properties of Surfactants in Petroleum Production and Geological Storage Systems from a Molecular Scale Perspective.

Surfactants play a crucial role in tertiary oil recovery by reducing the interfacial tension between immiscible phases, altering surface wettability, and improving foam film stability. Oil reservoirs have high temperatures and high pressures, making it difficult and hazardous to conduct lab experiments. In this context, molecular dynamics (MD) simulation is a valuable tool for complementing experiments. It can effectively study the microscopic behaviors (such as diffusion, adsorption, and aggregation) of the surfactant molecules in the pore fluids and predict the thermodynamics and kinetics of these systems with a high degree of accuracy. MD simulation also overcomes the limitations of traditional experiments, which often lack the necessary temporal-spatial resolution. Comparing simulated results with experimental data can provide a comprehensive explanation from a microscopic standpoint. This article reviews the state-of-the-art MD simulations of surfactant adsorption and resulting interfacial properties at gas/oil-water interfaces. Initially, the article discusses interfacial properties and methods for evaluating surfactant-formed monolayers, considering variations in interfacial concentration, molecular structure of the surfactants, and synergistic effect of surfactant mixtures. Then, it covers methods for characterizing microstructure at various interfaces and the evolution process of the monolayers' packing state as a function of interfacial concentration and the surfactants' molecular structure. Next, it examines the interactions between surfactants and the aqueous phase, focusing on headgroup solvation and counterion condensation. Finally, it analyzes the influence of hydrophobic phase molecular composition on interactions between surfactants and the hydrophobic phase. This review deepened our understanding of the micro-level mechanisms of oil displacement by surfactants and is beneficial for screening and designing surfactants for oil field applications.

Sterile Diet Causes Gut Microbiome Collapse of Cancer Patients Post Hematopoietic Cell Transplantation, But Normal Diet Recovers Them.

Though sterile diet, post-transplantation surgery is a clinical strategy for patient care to prevent the infiltration of gut pathogens, less is known about its effects on the gut microbiome. Here, the gut microbiome dynamics of leukemia patients following a 120-day "sterile-normal" diet strategy posthematopoietic cell transplantation are examined. In contrast to the traditional idea, a sterile diet leads to the lowest gut microbiota diversity (p < 0.05) and short-chain fatty acids, promoted the proliferation of potential pathogens such as Streptococcus (up by 16.93%) and Lactobacillus (up by 40.30%), and 43.32% reduction in nodes and an 85.33% reduction in edges within the microbial interaction's network. Interestingly, a normal diet allows the gut microbiome recovery and significantly promotes the abundance of beneficial bacteria. These results indicate that a sterile diet leads to a collapse of the patient's gut microbiome and promoted the proliferation of potential pathogens. This assay is a starting point for a more sophisticated assessment of the effects of a sterile diet. The work also suggests a basic principle for the re-establishment of microbial equilibrium that supplementation of microbial taxa may be the key to the restoration of the degraded ecosystem.

KLF13 restrains Dll4-muscular Notch2 axis to improve the muscle atrophy.

BACKGROUND: Muscle atrophy can cause muscle dysfunction and weakness. Krüppel-like factor 13 (KLF13), a central regulator of cellular energy metabolism, is highly expressed in skeletal muscles and implicated in the pathogenesis of several diseases. This study investigated the role of KLF13 in muscle atrophy, which could be a novel therapeutic target. METHODS: The effects of gene knockdown and pharmacological targeting of KLF13 on skeletal muscle atrophy were investigated using cell-based and animal models. Clofoctol, an antibiotic and KLF13 agonist, was also investigated as a candidate for repurposing. The mechanisms related to skeletal muscle atrophy were assessed by measuring the expression levels and activation statuses of key regulatory pathways and validated using gene knockdown and RNA sequencing. RESULTS: In a dexamethasone-induced muscle atrophy mouse model, the KLF13 knockout group had decreased muscle strength (N) (1.77 ± 0.10 vs. 1.48 ± 0.16, P < 0.01), muscle weight (%) [gastrocnemius (Gas): 76.0 ± 5.69 vs. 60.7 ± 7.23, P < 0.001; tibialis anterior (TA): 75.8 ± 6.21 vs. 67.5 ± 5.01, P < 0.05], and exhaustive running distance (m) (495.5 ± 64.8 vs. 315.5 ± 60.9, P < 0.05) compared with the control group. KLF13 overexpression preserved muscle mass (Gas: 100 ± 6.38 vs. 120 ± 14.4, P < 0.01) and the exhaustive running distance (423.8 ± 59.04 vs. 530.2 ± 77.45, P < 0.05) in an in vivo diabetes-induced skeletal muscle atrophy model. Clofoctol treatment protected against dexamethasone-induced muscle atrophy. Myotubes treated with dexamethasone, an atrophy-inducing glucocorticoid, were aggravated by KLF13 knockout, but anti-atrophic effects were achieved by inducing KLF13 overexpression. We performed a transcriptome analysis and luciferase reporter assays to further explore this mechanism, finding that delta-like 4 (Dll4) was a novel target gene of KLF13. The KLF13 transcript repressed Dll4, inhibiting the Dll4-Notch2 axis and preventing muscle atrophy. Dexamethasone inhibited KLF13 expression by inhibiting myogenic differentiation 1 (i.e., MYOD1)-mediated KLF13 transcriptional activation and promoting F-Box and WD repeat domain containing 7 (i.e., FBXW7)-mediated KLF13 ubiquitination. CONCLUSIONS: This study sheds new light on the mechanisms underlying skeletal muscle atrophy and potential drug targets. KLF13 regulates muscle atrophy and is a potential therapeutic target. Clofoctol is an attractive compound for repurposing studies to treat skeletal muscle atrophy.

Transient chromatin decompaction at the start of D. melanogaster male embryonic germline development.

Embryonic germ cells develop rapidly to establish the foundation for future developmental trajectories, and in this process, they make critical lineage choices including the configuration of their unique identity and a decision on sex. Here, we use single-cell genomics patterns for the entire embryonic germline in Drosophila melanogaster along with the somatic gonadal precursors after embryonic gonad coalescence to investigate molecular mechanisms involved in the setting up and regulation of the germline program. Profiling of the early germline chromatin landscape revealed sex- and stage-specific features. In the male germline immediately after zygotic activation, the chromatin structure underwent a brief remodeling phase during which nucleosome density was lower and deconcentrated from promoter regions. These findings echoed enrichment analysis results of our genomics data in which top candidates were factors with the ability to mediate large-scale chromatin reorganization. Together, they point to the importance of chromatin regulation in the early germline and raise the possibility of a conserved epigenetic reprogramming-like process required for proper initiation of germline development.

Nuclear factors NF-YC3 and NF-YBs positively regulate arbuscular mycorrhizal symbiosis in tomato.

The involvement of nuclear factor Y (NF-Y) in transcriptional reprogramming during arbuscular mycorrhizal symbiosis has been demonstrated in several plant species. However, a comprehensive picture is lacking. We showed that the spatial expression of NF-YC3 was observed in cortical cells containing arbuscules via the cis-regulatory element GCC boxes. Moreover, the NF-YC3 promoter was transactivated by the combination of CYCLOPS and autoactive calcium and calmodulin-dependent kinase (CCaMK) via GCC boxes. Knockdown of NF-YC3 significantly reduced the abundance of all intraradical fungal structures and affected arbuscule size. BCP1, SbtM1, and WRI5a, whose expression associated with NF-YC3 levels, might be downstream of NF-YC3. NF-YC3 interacted with NF-YB3a, NF-YB5c, or NF-YB3b, in yeast (Saccharomyces cerevisiae) and in planta, and interacted with NF-YA3a in yeast. Spatial expression of three NF-YBs was observed in all cell layers of roots under both mock and mycorrhizal conditions. Simultaneous knockdown of three NF-YBs, but not individually, reduced the fungal colonization level, suggesting that there might be functional redundancy of NF-YBs to regulate AM symbiosis. Collectively, our data suggest that NF-YC3 and NF-YBs positively regulate AM symbiosis in tomato, and arbuscule-related NF-YC3 may be an important downstream gene of the common symbiosis signaling pathway.

Unexpected response of terrestrial carbon sink to rural depopulation in China.

China is experiencing large-scale rural-urban migration and rapid urbanization, which have had significant impact on terrestrial carbon sink. However, the impact of rural-urban migration and its accompanying urban expansion on the carbon sink is unclear. Based on multisource remote sensing product data for 2000-2020, the soil microbial respiration equation, relative contribution rate, and threshold analysis, we explored the impact of rural depopulation on the carbon sink and its threshold. The results revealed that the proportion of the rural population in China decreased from 63.91 % in 2000 to 36.11 % in 2020. Human pressure decreased by 1.82% in rural depopulation areas, which promoted vegetation restoration in rural areas (+8.45 %) and increased the carbon sink capacity. The net primary productivity (NPP) and net ecosystem productivity (NEP) of the vegetation in the rural areas increased at rates of 2.95 g C m-2 yr-1 and 2.44 g C m-2 yr-1. Strong rural depopulation enhanced the carbon sequestration potential, and the NEP was 1.5 times higher in areas with sharp rural depopulation than in areas with mild rural depopulation. In addition, the rural depopulation was accompanied by urban expansion, and there was a positive correlation between the comprehensive urbanization level (CUL) and NEP in 75.29 % of urban areas. In the urban areas, the vegetation index increased by 88.42 %, and the urban green space partially compensated for the loss of carbon sink caused by urban expansion, with a growth rate of 4.96 g C m-2 yr-1. Changes in rural population have a nonlinear impact on the NEP. When the rural population exceeds 545.686 people/km2, an increase in the rural population will have a positive impact on the NEP. Our research shows that rural depopulation offers a potential opportunity to restore natural ecosystems and thus increase the carbon sequestration capacity.

Exploring the mechanism of Scleromitrion diffusum (Willd.) in treating lung cancer based on network pharmacology and experimental validation.

This study aims to elucidate the mechanisms by which the effective components of Scleromitrion diffusum (Willd.) (SDW) treat lung cancer, using network pharmacology, in vitro cell experiments, and molecular docking methods. Network pharmacology techniques were employed to construct a network of SDW components, lung cancer targets, and signaling pathways. A proteinprotein interaction (P P I) network was built for target genes, identifying core gene targets. Signaling pathway and biological process analyses were conducted. MT T assays measured cell viability, and Western blot analysis assessed the impact of core protein targets and key pathway proteins on the stemness of three lung cancer cell lines. Molecular docking was performed to link SDW components with core proteins and key pathway targets related to lung cancer. SDW was found to target 88 genes and 5 active components (2-methoxy-3-methyl-9-10-anthraquinone, stigmasterol, beta-sitosterol, quercetin, and poriferasterol) relevant to lung cancer treatment. The P I3K/Akt and MEK/ERK pathways were identified as major signaling pathways. Extracts from SDW roots significantly inhibited the proliferation of three lung cancer cell lines (A549, HCC827, and NCIH-1395), primarily via P I3K/Akt and MEK/ERK pathways, significantly reducing the expression of p-Akt and p-Erk1/2 and slightly inhibiting caspase-9, p-P I3K, and EGFR expression. Molecular docking confirmed the strong binding activities of SDW components with lung cancer-related core proteins and key pathway targets. SDW may regulate apoptosis and proliferation in lung cancer treatment through P I3K-Akt and MAP K/ERK signaling pathways. The combination of network pharmacology, molecular docking, and experimental validation provides valuable insights into the molecular mechanisms of SDW in lung cancer therapy.

Epigallocatechin-3-gallate ameliorates lipopolysaccharide-induced acute thymus involution in mice via AMPK/Sirt1 pathway.

The thymus, a site to culture the naïve T lymphocytes, is susceptible to atrophy or involution due to aging, inflammation, and oxidation. Epigallocatechin-3-gallate (EGCG) has been proven to possess anti-inflammatory, antioxidant, and antitumor activity. Here, we investigate the effects of EGCG on thymic involution induced by lipopolysaccharide (LPS), an endotoxin derived from Gram-negative bacteria. The methodology included an in vivo experiment on female Kunming mice exposed to LPS and EGCG. Morphological assessment of thymic involution, immunohistochemical detection, and thymocyte subsets analysis by flow cytometry were further carried out to evaluate the potential role of EGCG on the thymus. As a result, we found that EGCG alleviated LPS-induced thymic atrophy, increased mitochondrial membrane potential and superoxide dismutase levels, and decreased malondialdehyde and reactive oxygen species levels. In addition, EGCG pre-supplement restored the ratio of thymocyte subsets, the expression of autoimmune regulator, sex-determining region Y-box 2, and Nanog homebox, and reduced the number of senescent cells and collagen fiber deposition. Western blotting results indicated that EGCG treatment elevated LPS-induced decrease in pAMPK, Sirt1 protein expression. Collectively, EGCG relieved thymus architecture and function damaged by LPS via regulation of AMPK/Sirt1 signaling pathway. Our findings may provide a new strategy on protection of thymus from involution caused by LPS by using EGCG. And EGCG might be considered as a potential agent for the prevention and treatment of thymic involution.

Blinatumomab in Children with MRD-Positive B-Cell Precursor Acute Lymphoblastic Leukemia: A Report of 11 Cases.

Background/Objectives: Relapsed B-cell acute lymphoblastic leukemia (B-ALL) remains an unresolved matter of concern regarding adverse outcomes. This case study aimed to evaluate the effectiveness of blinatumomab, with or without door lymphocyte infusion (DLI), in treating measurable residual disease (MRD)-positive B-ALL. Methods: All patients who received blinatumomab salvage therapy were included in this study. Eleven patients were included in the study. All patients were evaluated for MRD-negativity. Results: Before starting blinatumomab therapy, seven patients tested positive for MRD, three tested negative, and one had refractory disease. Hematopoietic cell transplantation (HCT) was reserved for five patients with persistent MRD. Six patients became MRD-negative and subsequent HCT was not performed. Only two patients relapsed; one patient died of relapse, and the other one received carfilzomib-based therapy and was MRD-negative thereafter. Nine patients were MRD-negative at a median follow-up of 28 months (15-52 months). Two of three MRD-positive post-transplant patients remained in complete molecular remission after preemptive DLI at the last follow-up date. In the first salvage, blinatumomab may achieve complete remission and bridging to HCT in pediatric patients with end-of-induction MRD-positive B-cell precursor ALL. Conclusions: The decision on how to treat post-transplant relapse continues to affect survival outcomes. Blinatumomab combined with DLI may extend the armamentarium of release options for high-risk pediatric patients. This approach is encouraging for high-risk ALL patients who are MRD-positive post-transplantation.

Interpretable deep clustering survival machines for Alzheimer's disease subtype discovery.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that has impacted millions of people worldwide. The neuroanatomical heterogeneity of AD has made it challenging to fully understand the disease mechanism. Identifying AD subtypes during the prodromal stage and determining their genetic basis would be immensely valuable for drug discovery and subsequent clinical treatment. Previous studies that clustered subgroups typically used unsupervised learning techniques, neglecting the survival information and potentially limiting the insights gained. To address this problem, we propose an interpretable survival analysis method called Deep Clustering Survival Machines (DCSM), which combines both discriminative and generative mechanisms. Similar to mixture models, we assume that the timing information of survival data can be generatively described by a mixture of parametric distributions, referred to as expert distributions. We learn the weights of these expert distributions for individual instances in a discriminative manner by leveraging their features. This allows us to characterize the survival information of each instance through a weighted combination of the learned expert distributions. We demonstrate the superiority of the DCSM method by applying this approach to cluster patients with mild cognitive impairment (MCI) into subgroups with different risks of converting to AD. Conventional clustering measurements for survival analysis along with genetic association studies successfully validate the effectiveness of the proposed method and characterize our clustering findings.