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Background & aims: Sarcopenia, a prevalent condition, significantly impacts the prognosis of patients with decompensated cirrhosis (DC). Serum fibroblast growth factor 21 (FGF21) levels are significantly higher in DC patients with sarcopenia. Satellite cells (SCs) play a role in aging- and cancer-induced sarcopenia. Here, we investigated the roles of FGF21 and SCs in DC-related sarcopenia as well as the underlying mechanisms. Methods: We developed two DC mouse models and performed in vivo and in vitro experiments. Klotho beta (KLB) knockout mice in SCs were constructed to investigate the role of KLB downstream of FGF21. In addition, biological samples were collected from patients with DC and control patients to validate the results. Results: Muscle wasting and impaired SC myogenesis were observed in the DC mouse model and patients with DC. Elevated circulating levels of liver-derived FGF21 were observed, which were significantly negatively correlated with skeletal muscle mass/skeletal muscle index. Liver-secreted FGF21 induces SC dysfunction, contributing to sarcopenia. Mechanistically, FGF21 in the DC state exhibits enhanced interactions with KLB on SC surfaces, leading to downstream phosphatase and tensin homolog upregulation. This inhibits the protein kinase B (PI3K/Akt) pathway, hampering SC proliferation and differentiation, and blocking new myotube formation to repair atrophy. Neutralizing circulating FGF21 using neutralizing antibodies, knockdown of hepatic FGF21 by adeno-associated virus, or knockout of KLB in SCs effectively improved or reversed DC-related sarcopenia. Conclusions: Hepatocyte-derived FGF21 mediates liver-muscle crosstalk, which impairs muscle regeneration via the inhibition of the PI3K/Akt pathway, thereby demonstrating a novel therapeutic strategy for DC-related sarcopenia.

Acetaminophen (APAP) overdose is a prevalent cause of clinical pharmacological liver injury worldwide. Artemether (ART), a first-line antimalarial drug, has demonstrated hepatoprotective activity. However, its effect on APAP-induced acute liver injury (AILI) remains unclear. In this study, we investigated whether ART can protect against AILI and examined its underlying mechanisms. In vivo, ART mitigated APAP-induced liver histological changes, including mitochondrial damage, hepatocyte necrosis, hepatocyte apoptosis, and inflammatory infiltration. Additionally, ART reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in APAP-induced mice. ART also activated the Nrf2-HO-1/GPX4 signaling pathway, exerting antioxidant effects in both in vitro and in vivo models of AILI. To confirm Nrf2 as a target of ART in vivo, we pretreated C57BL/6 mice with the Nrf2 inhibitor, ML385. The results indicated that inhibiting Nrf2 diminishes the protective effect of ART against AILI. Overall, our findings suggest that ART's protective effect against AILI is mediated through the Nrf2-related antioxidant pathway.

Pervasive environmental pollutants, specifically particulate matter (PM2.5), possess the potential to disrupt homeostasis of female thyroid hormone (TH). However, the precise mechanism underlying this effect remains unclear. In this study, we established a model of PM2.5-induced thyroid damage in female rats through intratracheal instillation and employed histopathological and molecular biological methods to observe the toxic effects of PM2.5 on the thyroid gland. Transcriptome gene analysis and 16S rRNA sequencing were utilized to investigate the impact of PM2.5 exposure on the female rat thyroid gland. Furthermore, based on the PM2.5-induced toxic model in female rats, we evaluated its effects on intestinal microbiota, TH levels, and indicators of thyroid function. The findings revealed that PM2.5 exposure induced histopathological damage to thyroid tissue by disrupting thyroid hormone levels (total T3 [TT3], (P < 0.05); total T4 [TT4], (P < 0.05); and thyrotropin hormone [TSH], (P < 0.05)) and functional indices (urine iodine [UI], P > 0.05), thus further inducing histopathological injuries. Transcriptome analysis identified differentially expressed genes (DEGs), primarily concentrated in interleukin 17 (IL-17), forkhead box O (FOXO), and other signaling pathways. Furthermore, exposure to PM2.5 altered the composition and abundance of intestinal microbes. Transcriptome and microbiome analyses demonstrated a correlation between the DEGs within these pathways and the flora present in the intestines. Moreover, 16 S rRNA gene sequencing analysis or DEGs combined with thyroid function analysis revealed that exposure to PM2.5 significantly induced thyroid hormone imbalance. We further identified key DEGs involved in thyroid function-relevant pathways, which were validated using molecular biology methods for clinical applications. In conclusion, the homeostasis of the ''gut-thyroid'' axis may serve as the underlying mechanism for PM2.5-induced thyrotoxicity in female rats.

Wild soybeans retain many substances significantly reduced or lost in cultivars during domestication. This study utilized LC-MS to analyze metabolites in the seed coats and embryos of wild and cultivated soybeans. 866 and 815 metabolites were identified in the seed extracts of both soybean types, with 35 and 10 significantly differing metabolites in the seed coat and embryos, respectively. The upregulated metabolites in wild soybeans are linked to plant defense, stress responses, and nitrogen cycling. MALDI-MSI results further elucidated the distribution of these differential metabolites in the cotyledons, hypocotyls, and radicles. In addition to their role in physiological processes like growth and response to environmental stimuli, the prevalent terpenoids, lipids, and flavonoids present in wild soybeans exhibit beneficial bioactivities, including anti-inflammatory, antibacterial, anticancer, and cardiovascular disease prevention properties. These findings underscore the potential of wild soybeans as a valuable resource for enhancing the nutritional and ecological adaptability of cultivated soybeans.

A holistic understanding and careful balancing of different quality aspects can support sustainable, evidence-based decisions during the planning and realisation phases of a building. To this end, it is important to consider, whether and to what extent different quality aspects are interrelated in order to assess potential consequences of decisions. For this purpose, the Holistic Quality Model 2.0 is introduced, representing a second iteration of the Holistic Quality Model developed in recent studies. It incorporates two improvements. First, the integration of the economic quality aspect in addition to the technical, environmental and social quality aspects. Second, the development of an extended interrelations methodology to facilitate better identification and quantitative analysis of interrelations. These improvements and a corresponding case study emphasise the shift from the conventional practice of evaluating quality aspects in isolation towards a holistic approach enabling informed decision-making by considering and balancing different quality aspects.

ABSTRACT: Avian pathogenic Escherichia coli (APEC) cause avian colibacillosis and accurately distinguishing infectious isolates is critical for controlling its transmission. Multilocus sequence typing (MLST) is an accurate and efficient strain identification method for epidemiological surveillance. This research aimed to develop a fast and high-throughput workflow that simultaneously sequences the Achtman typing scheme's 7 housekeeping genes of multiple E. coli isolates using the Oxford Nanopore Technologies (ONT) platform for large-scale APEC study. E. coli strains were isolated from poultry farms, the housekeeping genes were amplified, and amplicons were sequenced on an R9.4 MinION flow cell using the Nanopore GridION sequencer (ONT, Oxford, UK) following the initial workflow (ONT-MLST). Moreover, the workflow was revised by introducing large-scale DNA extraction and multiplex PCR into the ONT-MLST workflow and applied to 242 new isolates, 18 isolates from the previous workflow, and 5 ATCC reference strains using Flongle flow cell on the Nanopore MinION Mk1C sequencer (ONT, Oxford, UK). Finally, the sequence type (ST) results of the 308 isolates collected from infected chickens and poultry farm environments were reported and analyzed. Data indicated that E. coli belonging to ST159, ST8578, and ST355 have the potential to infect multiple organs in broiler. In addition, zoonotic STs, ST69, ST10, ST38, and ST131, were detected from poultry farms. With the advantages of the high throughput of ONT, this study provides a rapid workflow for large-scale E. coli typing and identified frequently isolated sequence types related to APEC infection in poultry.

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

BackgroundsCrush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures.MethodsMice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols.ResultsThe results showed that with the crushing weight increased, the kidney function assessment’s gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state.ConclusionWe successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI.

ABSTRACT Background Dexamethasone (Dex), a synthetic glucocorticoid that acts by binding to the glucocorticoid receptor (GR), has been widely applied to treat leukemia and lymphoma; however, the precise mechanism underlying Dex action is still not well elucidated. DOT1L, a histone H3‐lysine79 (H3K79) methyltransferase, has been linked to multiple cancer types, particularly mixed lineage leukemia (MLL) gene rearranged leukemia, but its contribution to lymphoma is yet to be delineated. Analysis from the TCGA database displayed that DOT1L was highly expressed in lymphoma and leukemia. Results We initially demonstrated that DOT1L served as a new target gene controlled by GR, and the downregulation of DOT1L was critical for the killing of B‐lymphoma cells by Dex. Further study revealed that Dex had no impact on the transcriptional activity of the DOT1L promoter, rather it reduced the mRNA level of DOT1L at the posttranscriptional level. In addition, knockdown of DOT1L remarkably inhibited the B‐lymphoma cell growth. Conclusions Overall, our findings indicated that DOT1L may serve as a potential drug target and a promising biomarker of Dex sensitivity when it comes to treating B lymphoma.

IntroductionTo investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms.Methods56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR.Results654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI.DiscussionThis study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock.

The thermal hazards generated during the tunnel boring machine construction process significantly impact the physical and mental health of personnel. A field test was conducted on the tunnel of Metro Line 1 in Changsha, China, where the average temperature in the work zone reached up to 33.16 °C, and the air velocity was generally below 0.2 m/s. These conditions were unfavorable for ventilation and heat dissipation. In this paper, a full-scale CFD simulation model was established to simulate the construction environment and analyze the cooling demand. The results indicated that increasing the fresh air velocity could lower the temperature in the work zone; however, this effect was limited. When the fresh air temperature exceeded a certain threshold, it actually raised the average temperature of the work zone. Consequently, there is a need for supplementary cooling of the fresh air during the hot summer months. At a fresh air velocity of 15 m/s, the maximum temperature in the work zone was recorded at 27.8 °C when the fresh air was cooled down to 22.5 °C through auxiliary cooling measures. This approach effectively controlled the temperature in the work zone, reduced flow dead zones, and significantly improved air distribution and heat dissipation. Additionally, it ensured the physical and mental well-being of the construction workers and the safe operation of the equipment. This study provides valuable guidance for managing thermal environments in underground tunnel construction.

Introduction: Previous results from the phase 3 ALESIA study (NCT02838420) revealed that alectinib (a central nervous system [CNS]-active, ALK inhibitor) had clinical benefits in treatment-naïve Asian patients with advanced ALK-positive NSCLC, consistent with the global ALEX study. We present updated data after more than or equal to 5 years of follow-up from the “last patient in” date. Methods: Adult patients with treatment-naïve, advanced ALK-positive NSCLC from mainland China, South Korea, and Thailand were randomized 2:1 to receive twice-daily 600 mg alectinib (n = 125) or 250 mg crizotinib (n = 62). The primary endpoint was investigator-assessed progression-free survival. Secondary or exploratory endpoints included overall survival, objective response rate, time to CNS progression, and safety. Results: At the data cutoff (May 16, 2022), the median survival follow-up was 61 and 51 months in the alectinib and crizotinib arms, respectively. Median progression-free survival was 41.6 months with alectinib versus 11.1 months with crizotinib (stratified hazard ratio = 0.33, 95% confidence interval: 0.23–0.49). Overall survival data remain immature; 5-year overall survival rates were 66.4% (alectinib arm) versus 56.1% (crizotinib arm). Objective response rate was 91.2% versus 77.4% with alectinib and crizotinib, respectively. CNS progression was delayed with alectinib versus crizotinib (cause-specific hazard ratio = 0.16, 95% confidence interval: 0.08–0.32). Median treatment duration was longer with alectinib versus crizotinib (42.3 versus 12.6 mo). No new safety signals were observed. Conclusions: With four additional years of follow-up, these updated results confirm the clinical benefit and manageable safety of alectinib in Asian patients with advanced ALK-positive NSCLC, and confirm alectinib as a standard-of-care treatment for patients with advanced ALK-positive NSCLC.

ABSTRACT Introduction Acute lung injury (ALI) is a critical and lethal medical condition. This syndrome is characterized by an imbalance in the body's oxidation stress and inflammation. Linoleic acid (LA), a polyunsaturated fatty acid, has been extensively studied for its potential health benefits, including anti‐inflammatory and antioxidant activities. However, the therapeutic effects of LA on ALI remain unexplored. Methods Lipopolysaccharide (LPS), found in gram‐negative bacteria's outer membrane, was intraperitoneally injected to induce ALI in mice. In vitro model was established by LPS stimulation of mouse lung epithelial 12 (MLE‐12) cells. Results LA treatment demonstrated a significant amelioration in LPS‐induced hypothermia, poor state, and pulmonary injury in mice. LA treatment resulted in a reduction in the concentration of bronchoalveolar lavage fluid (BALF) protein and an increase in myeloperoxidase (MPO) activity in LPS‐induced mice. LA treatment reduced the generation of white blood cells. LA treatment reduced cell‐free (cfDNA) release and promote adenosine triphosphate (ATP) production. LA increased the levels of superoxide dismutase (SOD) and glutathione (GSH) but decreased the production of malondialdehyde (MDA). LA treatment enhanced mitochondrial membrane potential. LA attenuated LPS‐induced elevations of inflammatory cytokines in both mice and cells. Additionally, LA exerted its protective effect against LPS‐induced damage through activation of the peroxisome proliferator‐activated receptor γ coactivator l alpha (PGC‐1α)/nuclear respiratory factor 1 (NRF1)/transcription factor A of the mitochondrion (TFAM) pathway. Conclusion LA may reduce inflammation and stimulate mitochondrial biogenesis in ALI mice and MLE‐12 cells.

BackgroundThis study aims to explore the association between sleep duration and the prevalence of chronic musculoskeletal pain (CMP).MethodsA cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2009–2010, which involved multiple centers across the United States. The study included 3,904 adults selected based on age and complete data availability. Demographic variables such as gender, age, race, and socioeconomic status (represented by the poverty-to-income ratio) were considered.ResultsOf the participants, 1,595 reported less than 7 h of sleep, 2,046 reported 7–8 h, and 263 reported more than 9 h of sleep. Short sleep duration was associated with higher odds of CMP (OR, 1.611, 95% CI: 1.224–2.120, p = 0.005). Long sleep duration also showed a higher prevalence (OR, 1.751; 95% CI, 0.923 to 3.321; p = 0.059), although this result was not statistically significant. A U-shaped relationship emerged (Effective degree of freedom (EDF) = 3.32, p

Abstract Background Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high‐risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively. Methods In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the β‐value of the corresponding regression coefficient. A predictive risk‐scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21‐involved risk with the established R‐ISS and R2‐ISS models. Results Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p

Objective: This study aim to quantify the differences in knee biomechanics during gait between knee osteoarthritis (KOA) patients and healthy individuals. Methods: Twenty KOA patients (4 males and 16 females, 66.2 ± 7.7 years) and twenty controls (16 males and 4 females, 64.8 ± 5.4 years) were recruited for gait test using the motion capture system and force-platform system. The spatiotemporal parameters, knee kinematics and kinetics, and tibiofemoral contact force (TFCF) were calculated using an improved musculoskeletal model. Results: KOA patients walked with reduced speed (48.6 %), stride length (32.9 %), stride height (33.0 %), time proportions of single-support phases (19.2 %), increased gait cycle time (31.0 %), time proportions of stance (8.5 %) and double-support phases (57.7–75.9 %). KOA patients had significant smaller peak flexion angle (29.1 %), flexion ROM (50.6 %) and peak flexion moment (90.2 %), greater peak adduction moment (KAM) (40.7 %), peak rotation moments (KRM) (50.0 %), KAM impulse (106.2 %) and KRM impulse (126.0 %). In proximodistal direction, greater medial TFCF impulse (238 %), total and medial first-peak TFCF (9.6 % and 15.2 %), and smaller lateral peak TFCF (33.3 %) and TFCF impulse (38.4 %) were found in KOA patients. Besides, significant differences were found in the total, medial and lateral peak TFCFs and TFCF impulses in mediolateral direction, and the medial and lateral TFCFs and TFCF impulses in anteroposterior direction. Conclusions: Significant differences were found in the spatiotemporal parameters, knee kinematics and kinetics, and TFCF between the two groups. The results of this study have important implication for clinicians and rehabilitation physicians. These quantified biomechanical differences can provide data support for the personalized and quantified rehabilitation strategies, give suggestions for the exercises of KOA patients, help monitor disease, evaluate surgical treatment, and develop more effective preoperative planning and postoperative rehabilitation strategies.

Pseudorabies virus (PRV) exhibits a complex interplay of host-pathogen interactions, primarily by modulating host cell death pathways to optimize its replication and spread in Neuro-2a cells. Using high-throughput RNA sequencing, we identified 2,382 upregulated differentially expressed genes (DEGs) and 3,998 downregulated DEGs, indicating a intricate interaction between viral pathogenesis and host cellular responses. This research offers valuable insights into the molecular processes involved in PRV infection, highlighting the substantial inhibition of crucial cell death pathways in Neuro-2a cells, including necroptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis. Cells infected with PRV exhibit decreased expression of genes critical in these pathways, potentially as a mechanism to avoid host immune reactions and ensure cell survival to support ongoing viral replication. This extensive inhibition of apoptosis and metabolic alterations highlights the sophisticated tactics utilized by PRV, enhancing our comprehension of herpesvirus biology and the feasibility of creating specific antiviral treatments. This research contributes to our understanding of how viruses manipulate host cell death and presents potential opportunities for therapeutic interventions to disrupt the virus’s lifecycle.

Long-term continuous cropping of tobacco causes dysbiosis of soil microbial communities, the imbalance of soil nutrients, and the increase of pathogenic bacteria, which will slow the growth and development of tobacco plants, reduce the production quality, and cause significant losses to tobacco production and tobacco farmers. The application of Potassium fulvic acid can not only provide nutrients, but also inhibit the propagation of pathogens in soil along with raising the amount of organic matter in the soil, which is an effective way to improve soil health. In this experiment, Tobacco variety SNT60 was used as the test material, and 6 treatments were set up by pot test, they were: no fertilisation control group (CK), tobacco special fertiliser (NPK), 3.45 g/kg of potassium fulvic acid fertiliser (T1), 4.65 g/kg of potassium fulvic acid fertiliser (T2), 5.85 g/kg of potassium fulvic acid fertiliser (T3), 7.05 g/kg of potassium fulvic acid fertiliser (T4), Ten replications were set up for each treatment and the soil and fertiliser were mixed and potted before transplanting, 70% as basal fertiliser and 30% as supplementary fertiliser. We also analyzed soil properties, soil microorganisms and agronomic traits of tobacco plants in different treatments to provide reference for mitigating tobacco succession barrier. The test results are as follows: 4.65 g/kg of potassium fulvic acid fertiliser (T2) treatment was the best, soil organic matter, quick nitrogen, phosphorus, potassium, pH, soil catalase, soil sucrase, and soil urease content, compared to CK control, increased by 22.04%, 43.12%, 96.21%, 381.79%, 25.43%, 91.69%, 262.07% and 93.16%. In terms of microbial community, application of potassium fulvic acid fertiliser significantly increased the relative abundance of Ascomycetes, Chlorobacterium, Bacillus, Proteobacteria and Tephritobacterium in the soil. Meanwhile, 4.65 g/kg of potassium fulvic acid fertiliser (T2) promoted the growth of tobacco plants, improved leaf photosynthetic capacity, and enhanced plant disease resistance. This experiment provides practical measures to improve the microbial community of tobacco continuous cropping soils and to reduce the incidence of diseases.

Plant growth, crop yield, and pest and disease control are enhanced by PGPR (Plant growth promoting rhizobacteria), which are beneficial microorganisms found in a close symbiosis with plant roots. Phytohormones are secreted, nutrient uptake is improved, and soil properties along with the microbiological environment are regulated by these microorganisms, making them a significant focus in agricultural research. In this study, the efficient PGPR strain T1 was isolated and screened from tobacco inter-root soil, and identified and confirmed by ITS sequencing technology. Tobacco growth indicators and soil property changes were observed and recorded through potting experiments. The activities of key enzymes (e.g., sucrase, catalase, urease) in soil were further determined. High-throughput sequencing technology was utilized to sequence the soil microbial community, and combined with macro-genomics analysis, the effects of T1 strain on soil microbial diversity and metabolic pathways were explored. Following the application of T1, significant improvements were observed in the height, leaf length, and width of tobacco plants. Furthermore, the physical and chemical properties of the soil were notably enhanced, including a 26.26% increase in phosphorus availability. Additionally, the activities of key soil enzymes such as sucrase, catalase, and urease were significantly increased, indicating improved soil health and fertility. Comprehensive joint microbiomics and macrogenomics analyses revealed a substantial rise in the populations of beneficial soil microorganisms and an enhancement in metabolic pathways, including amino acid metabolism, synthesis, and production of secondary metabolites. These increase in beneficial microorganisms and the enhancement of their metabolic functions are crucial for plant growth and soil fertility. This study provides valuable references for the development of innovative microbial fertilizers and offers programs for the sustainable development of modern agriculture.

ObjectiveCirculating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial.Research design and methodsA subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years.ResultsIn fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models.DiscussionThis study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.

Background Although chemoradiotherapy is an effective treatment for esophageal cancer, its feasibility in esophageal cancer with cirrhosis remains largely unclear. Methods We retrospectively studied 11 patients with superficial esophageal cancer with liver cirrhosis (Child-Pugh score ≤8) who underwent radical chemoradiotherapy from four centers, and the overall survival rate, local control rate and adverse events at 1 and 3 years were explored. Results The median age of the included patients was 67 years (Inter-Quartile Range 60–75 years). Complete response was observed in most patients (n = 10, 90.9%), and the remaining patient was unevaluable. The 1- and 3-year overall survival and local control rates were 90.9% and 90.9%, and 72.7% and 63.6%, respectively. Hematotoxicity was a common adverse reaction, and seven patients developed radiation esophagitis, with grade 3–4 observed in two cases. All cases of radiation dermatitis (n = 4) and radiation pneumonia (n = 2) were grade 1–2. Gastrointestinal bleeding occurred in two patients, including one with grade 1–2 bleeding, and one died. Conclusion Radical chemoradiotherapy is a potential treatment option for patients with superficial esophageal cancer complicated with cirrhosis. However, it can increase the risk of bleeding, which warrants prompt recognition and intervention.

This study aims to elucidate the anti-hypoxia mechanism of sesamoside, an active component of Phlomis younghusbandii Mukerjee , through a network pharmacology approach. Sesamoside has demonstrated potential anti-oxidant and antiglycation activities. The hypoxia-related disease targets were collected from databases like GeneCards and OMIM. Protein-protein interaction (PPI) networks were constructed using the STRING database. GO/KEGG enrichment analysis was performed using the Metascape database to identify biological processes and signaling pathways. Our results indicate that sesamoside interacts with multiple targets related to glucose and lipid metabolism, nucleotide metabolism, and inflammatory, and we find that AKR1B1 (AR) plays a crucial role in sesamoside responses to hypoxia. Molecular docking studies were performed using Autodock software, revealing good binding activity between sesamoside and AR. We then use CCK-8 assay, qPCR, WB, and ELISA analysis to validate the role of sesamoside in regulating AR and participating in anti-hypoxia through cell experiments. The results show that compared with the hypoxia group, sesamoside treatment significantly improves the expression of AR and inflammation cytokines. In summary, this study sheds light on the anti-hypoxia mechanism of sesamoside using a network pharmacology approach, providing a theoretical basis and experimental foundation for its application in the prevention and treatment of hypoxic diseases.

Background: Ischaemia–reperfusion injury (IRI) is a critical complication post-limb replantation. The oxidative stress and cellular apoptosis due to IRI considerably hinder the healing process. This study aimed to investigate the modulatory effects of pre-perfusion with hydrogen-rich heparin sodium on the nuclear factor erythroid 2–related factor 2 (NRF2)/haeme oxygenase-1 (HO-1) pathway and its potential mechanisms in mitigating skeletal muscle IRI post-limb replantation. Methods: Forty healthy Sprague–Dawley rats (250–300 g) were classified into five groups (n = 8 each): normal control, IRI + heparin sodium pre-perfusion (heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion (hydrogen-rich heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion + NRF2 inhibitor (hydrogen-rich heparin + all-trans retinoic acid [ATRA] group), and IRI + heparin sodium pre-perfusion + NRF2 inhibitor (heparin + ATRA group). The activation of the NRF2/HO-1 pathway in skeletal muscle IRI was evaluated based on HO-1 expression using western blotting and immunofluorescence. Furthermore, haematoxylin and eosin staining and transmission electron microscopy were employed to determine the histopathological characteristics. Additionally, superoxide dismutase and malondialdehyde levels in skeletal muscle tissue were measured to assess antioxidant capacity and the degree of oxidative stress damage. Tissue hypoxia was assessed based on hypoxia-inducible factor 1-alpha expression, whereas apoptosis markers BCL-2-associated X protein (BAX) and Caspase-3 in skeletal muscle tissues were analysed using western blotting with terminal deoxynucleotidyl transferase dUTP nick end labelling staining to quantify cell apoptosis. Results: Compared with the control group, the heparin group exhibited significant pathological changes, including inflammatory infiltration and cellular hypertrophy, with increased apoptosis and oxidative stress. Notably, NRF2 suppression aggravated these effects. However, hydrogen-rich heparin sodium prominently activated the NRF2/HO-1 pathway, enhancing antioxidant defence and reducing BAX/Caspase-3-mediated apoptosis, thereby mitigating IRI-induced damage. The use of an NRF2 inhibitor to inhibit NRF2 excitation by hydrogen-rich heparin sodium notably weakened NRF2 activation and the antioxidant response, resulting in a substantial increase in cellular apoptosis. Conclusion: Pre-perfusion with hydrogen-rich heparin sodium markedly diminishes the BAX/Caspase-3-mediated apoptotic pathway in skeletal muscle tissues with IRI through the excitation of the NRF2/HO-1 pathway.

Understanding how the bacteriomes in tuberculous lesions can be influenced by the susceptibility of Mycobacterium tuberculosis (MTB) can provide valuable information for preventing and treating drug resistant tuberculosis (DR-TB). High-throughput 16S rRNA sequencing was employed to analyze the bacteriome in pulmonary TB lesions from 14 patients with DR-TB and 47 patients with drug sensitive tuberculosis (DS-TB), along with 18 normal lung tissues (NT) from 18 lung cancer patients serving as the bacterial baseline. The phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) algorithm was utilized to predict bacterial metabolic functions. The major phyla of pulmonary bacteriomes included Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Fusobacteria. Alpha diversity indices, including ACE, Chao1, Shannon and OTU observed, all demonstrated different bacterial communities of DS-TB samples from that of NT samples; while only Shannon indicated difference between DR-TB and NT samples. The analysis of similarity (ANOSIM) showed significantly different bacterial communities within TB lesions compared to NT samples (R = 0.418, p = 0.001). However, difference was not observed between DR-TB and DS-TB samples (ANOSIM, R = 0.069, p = 0.173). The bacterial profiles within each DR-TB individual appeared unique, with no obvious clusters corresponding to drug-resistant phenotypes. Nevertheless, indicator genera identified in DR-TB and DS-TB lesions demonstrated distinctive micro-ecological environments. Most COG functions were enriched in TB lesions, and the most significant one was [J] translation, ribosomal structure and biogenesis. The distinct enrichment patterns of bacterial enzymes in DR-TB and DS-TB lesions suggest that pulmonary bacterial activities can be modulated by the susceptibility of MTB bacilli. This study provides fresh perspectives and strategies for the precise diagnosis and assessment of drug resistance tuberculosis.

Degradation, fragmentation, and habitat loss significantly threaten the survival of giant pandas (Ailuropoda melanoleuca). Habitat suitability evaluations (HSEs) represent a crucial component of giant panda habitat research. However, a systematic review of HSE research on giant pandas has not been conducted in recent years. To make up for that, we synthesised HSE research on giant pandas publicated from 2013 to 2022 and conducted a comprehensive analysis of the evaluation scale, evaluation methods, and research findings. We found a correlation between the geographical distribution of giant pandas and HSE-based studies on giant pandas. Furthermore, we observed a trend towards interdisciplinary and large-scale research. Although the evaluation accuracy has improved compared to that of earlier work, some limitations still remain, such as concentrated evaluation areas, incomplete indicators, and outdated data. Current HSE research on giant pandas helps determine suitable habitat distributions, facilitating protection strategies and management planning for protected areas. We suggest that future research should prioritize those unexplored or under-evaluated areas, incorporate a broader range of microenvironmental indicators, and update data resources and methodologies. This study bridges the gap in systematic reviews on HSEs of the giant panda and provides valuable references and recommendations for future research as well as the protection and management of giant panda habitats.

Objective: This study aimed to verify whether pancreatic steatosis (PS) is an independent risk factor for type 2 diabetes mellitus (T2DM). We also developed and validated a deep learning model for the diagnosis of PS using ultrasonography (US) images based on histological classifications. Methods: In this retrospective study, we analysed data from 139 patients who underwent US imaging of the pancreas followed by pancreatic resection at our medical institution. Logistic regression analysis was employed to ascertain the independent predictors of T2DM. The diagnostic efficacy of the deep learning model for PS was assessed using receiver operating characteristic curve analysis and compared with traditional visual assessment methodology in US imaging. Results: The incidence rate of PS in the study cohort was 64.7 %. Logistic regression analysis revealed that age (P = 0.003) and the presence of PS (P = 0.048) were independent factors associated with T2DM. The deep learning model demonstrated robust diagnostic capabilities for PS, with areas under the curve of 0.901 and 0.837, sensitivities of 0.895 and 0.920, specificities of 0.700 and 0.765, accuracies of 0.814 and 0.857, and F1-scores of 0.850 and 0.885 for the training and validation cohorts, respectively. These metrics significantly outperformed those of conventional US imaging (P

BackgroundParkinson’s disease is characterized by symptoms such as bradykinesia and rigidity, which worsen as the disease progresses, significantly impacting patients’ independence and quality of life. This study utilizes a network meta-analysis approach to quantify information gathered from randomized controlled trials (RCTs) regarding motor interventions that effectively improve the motor function of Parkinson’s disease patients, aiming to provide evidence for selecting appropriate exercise intervention strategies for patients.MethodsA systematic search strategy for randomized controlled trials (RCTs) restricted to English was constructed based on multiple biomedical databases. Databases searched included PubMed, Embase, Cochrane, Web of Science, CINAHL, CBM, China National Knowledge Infrastructure (CNKI), Wan fang, VIP, etc., with searches conducted from inception to July 9, 2023. Two authors screened all studies, extracted data, and used frequency domain analysis methods. Network meta-analysis was performed using STATA software version 18.0 to compare and rank exercises that could effectively improve the motor function of Parkinson’s disease patients (measured by indicators such as MDS-UPDRS-III, TUG, BBS, Mini-BES Test, 6MWT scores). Additionally, a series of analyses and evaluations were conducted, such as assessing the methodological quality of included studies using the Cochrane risk of bias tool.ResultsThe network meta-analysis included a total of 111 studies involving 5,358 participants, 133 intervention experiments, and 31 intervention measures. Although most exercise interventions showed effectiveness, cumulative ranking curves under the surface (SUCRA) values showed that archery exercise significantly improved patients’ MDS-UPDRS-III scores (SUCRA = 95.6%), significantly superior to routine care [standardized mean difference (SMD = 16.92, 95%CI = −28.97, −4.87)]. High-intensity and agility exercise (High strength and agility) referred to as high-intensity exercise or agility training or a combination of both, collectively termed as high-intensity agility training, significantly improved patients’ completion time for the time-up-and-go test (SUCRA = 99.7%), (SMD = −7.88, 95%CI = −9.47, −6.28). Dance and Tai Chi exercises significantly improved patients’ balance abilities: Mini-Balance Evaluation Systems Test (SUCRA = 77.9%), (SMD = 5.25, 95%CI = −0.42, 10.92) for dance intervention and Berg Balance Scale (SUCRA = 94.7%), (SMD = 11.22, 95%CI = 3.26, 19.18) for Tai Chi intervention. Dance also significantly improved patients’ walking ability in the 6-min walk test (SUCRA = 80.5%), (SMD = 71.31, 95%CI = 13.77, 128.84).ConclusionCompared to other exercises, archery, dance, Tai Chi, and high-intensity agility exercises demonstrate superior efficacy in improving the motor function of Parkinson’s disease patients.

Summary: Microglia, as the immune cells of the central nervous system (CNS), play dynamic roles in both healthy and diseased conditions. The ability to genetically target microglia using viruses is crucial for understanding their functions and advancing microglia-based treatments. We here show that resident microglia can be simply and specifically targeted using adeno-associated virus (AAV) vectors containing a 466-bp DNA fragment from the human IBA1 (hIBA1) promoter. This targeting approach is applicable to both resting and reactive microglia. When combining the short hIBA1 promoter with the target sequence of miR124, up to 98% of transduced cells are identified as microglia. Such a simple and highly specific microglia-targeting strategy may be further optimized for research and therapeutics.

Summary: Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I–IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8–46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9–62.8) and 35.7% (95% CI 23.8–53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43–42.54, P

Turpan-Hami (Tuha) Basin is in an extremely arid area, surrounded by mountains and desert with sparse vegetation. It has experienced serious desertification over the past 30 years, resulting in ecological environment and socio-economic issues. To reveal the temporal and spatial evolutions of desertification degrees in Tuha Basin, we first constructed an evaluation system for the desertification degree classification using vegetation and soil-related indices; then long-time series Landsat 5 TM/ Landsat8 OLI images and a C5.0 decision tree (DT) model were used to monitor large-scale desertification from 1990 to 2020. We applied a geographic detector to discover the driving forces between desertification changes and natural and human factors. The results demonstrated that the severe desertification (SD) accounted for the largest desertification degree, and the transitions of various desertification degrees mainly occurred between extremely severe desertification (ESD) and SD, which were considered the most active degrees. Only 9.4 % of Tuha Basin showed an expansion trend in desertification degree, with the most significant expansion occurred in 1990–1995. The proportion of 13.6 % desertification showed a reversion trend, with the most significant reversion occurred in 1995–2010. The main driving factors affecting the evolution of desertification degrees were precipitation and temperature, with the average q value higher than 0.95. Human activity factors such as year-end cropland area and population also impacted the patterns of desertification degree, with the q values of 0.9 and 0.7, respectively. The interactive detection enhanced the driving forces and the interaction between precipitation and other factors played a leading role in desertification degree changes. The results provide scientific data and a basis for desertification control and ecological protection in arid areas.

In order to elucidate the sound source characteristics during the noise propagation process of converter transformers, a series of experimental studies were conducted based on finite element simulation and proportional prototype design of converter transformers. It was found that it was unreasonable to equate converter transformers with point sound sources in previous studies. On the contrary, it should be divided into dipole and multipole distribution characteristics. Meanwhile, research has found that the noise distribution of converter transformers exhibits dipole and dipole distribution characteristics under power frequency and harmonic excitation, respectively. The contribution of harmonic components at different frequencies in the formation process of bipolar sound sources was quantified through simulation and experiments, and the key harmonic frequencies for forming multipole sound sources were determined as paired combinations of 5, 7, 11, 13, 23, and 25. Based on the above research conclusions, a noise reduction approach for converter transformers based on bipolar and multipole boundary effects is proposed.

Background: Stroke is the second leading cause of death for all human beings and poses a serious threat to human health. Environmental exposure to a mixture of metals may be associated with the occurrence and development of stroke, but the evidence in the Chinese population is not yet conclusive. Objectives: This study evaluated the association between stroke risk and 13 metals Methods: Metal concentrations in whole blood samples from 100 stroke cases and 100 controls were measured by ICP-MS. The cumulative impact of mixed metal on stroke risk was investigated by using three statistical models, BKMR, WQS and QGC. Results: The case group had higher concentrations of Mg, Mn, Zn, Se, Sn, and Pb than the control group (p

With the development of artificial intelligence technology and Unmanned Aerial Vehicle (UAV) technology, the traditional UAV target detection methods are difficult to achieve high detection accuracy in complex and changeable scenes. The paper selects Faster Region Convolutional Neural Network (Faster R-CNN) as the basic algorithm due to its high scalability and excellent classification performance. The convolution mode of the convolution layer in the network structure is adjusted to deformable convolution. Additionally, a hybrid attention mechanism module is added to combine channel attention and spatial attention modules behind the output layer of the Faster R-CNN network. Finally, the Soft Non-Maximum Suppression (Soft-NMS) method is selected to combine the improved Faster R-CNN algorithm of multiple individuals into the final target detection model. The performance of the improved Faster R-CNN algorithm and the original Faster R-CNN algorithm was verified through the VisDrone 2018-DET dataset and the full class average accuracy Mean Average Precision (mAP), accuracy and precision. The accuracy and logarithm of loss values of the improved Faster R-CNN algorithm and the original Faster R-CNN algorithm's Region Proposal Network (RPN) were 0.985, 0.981, 0.018, and 0.052, respectively. The target detection model based on the hybrid attention mechanism of ResNet-50 network fusion Spartial Attention Module (SAM) and Channel Attention Module (CAM) had the best classification performance, with the accuracy, precision and overall average accuracy of 25.8 %, 24.6 % and 22.7 %, respectively. The results are helpful to improve the target detection ability of UAV in complex environment, and contribute to the development of target detection technology in the future.

ABSTRACT: The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy that is involved in tumor genesis and development. However, few studies have focused on the predictive role of the global histone modification status in ccRCC. A total of 621 patients with complete transcript information and corresponding clinical profiles were obtained from TCGA-KIRC, GSE22541, and EMTAB3267 cohorts. A total of 122 histone modification relevant pathways were derived from MSigDB, and their activation status was quantified using GSVA. Differentially expressed genes (DEGs) were identified and filtrated using univariate Cox regression analysis. The signature was built relied on the least absolute shrinkage and selection operator (LASSO) regression analysis, and evaluated from survival difference, chemotherapy response, and activated pathways. A novel nomogram was established to quantify the probability of death in different patients. Seven risky and fifty-eight protective genes were used in LASSO analysis, and six genes were used to build the histone modification gene (HiMG) signature, which showed significant independent prognostic potential in all three cohorts. The nomogram showed acceptable incremental predictions. CKS2 (p = 0.004) and PD1 (p = 0.002) expression were significantly higher in grade 3 ccRCC than in grades 1–2. CKS2 siRNA in renal cancer cells caused reductions in cellular proliferation, migration, and invasion. Patients with low HiMG may be potential responders to rapamycin, erlotinib and FH535, while AZD6482 and CHIR-99,021 may be more suitable for patients with high HiMG levels. ccRCC histone modification distribution and a clinical signature for prognosis prediction, clinical decision making, and molecular mechanism exploration, were established for risk stratification and personalized treatments.

Isobavachalcone (IBC) as a bioactive chalcone isolated from the seeds of Psoralea corylifolia Linn has shown promising anticancer activities. However, its main anticancer mechanism in colorectal cancer cells has not been well-explored. Recently, the interaction of therapeutic compounds with survivin, an antiapoptotic marker, has been indicated to be a potential approach for advancing anticancer compounds. Therefore, in this study, IBC was evaluated for its anticancer activities against metastatic colorectal adenocarcinoma, LoVo, followed by exploring its interaction with survivin. It was observed that incubation of the human LoVo colorectal cancer cells with the IBC at 24 h resulted in a significant reduction in cell viability with an IC50 of about 35 µM as well as a significant membrane damage. Also, it was deduced that IBC could result in the formation of excessive ROS, lipid peroxidation, reduction of SOD/CAT activity, as well as downregulation of Nrf2 and HO-1 mRNA levels. Further studies showed that IBC could induce MMP reduction, cytochrome c (Cyt c) release, overexpression of Bax/Bcl-2 mRNA ratio as well as caspase-9 and −3. Moreover, it was deduced that IBC mitigated the expression of survivin at mRNA and protein levels. Then, binding parameters indicated that IBC strongly binds to one molecule of survivin at physiological temperature. Also, it was revealed that IBC substantially induced the conformational changes of survivin. Ultimately, through hydrogen bonding and hydrophobic forces, IBC has a substantial binding affinity with survivin (–9.80 kcal/mol) at a region that is critical to the dimerization process, according to molecular docking studies. Overall, this study showed that IBC may be used in future research to assess its clinical and in vivo behaviors in the modulation of colorectal cancer mediated by deactivation and downregulation of antiapoptotic survivin.

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. Familial cases of PD are often caused by mutations of PTEN-induced kinase 1 (PINK1) and the ubiquitin ligase Parkin, both pivotal in maintaining mitochondrial quality control. CISD1, a homodimeric mitochondrial iron-sulfur-binding protein, is a major target of Parkin-mediated ubiquitination. We here discovered a heightened propensity of CISD1 to form dimers in Pink1 mutant flies and in dopaminergic neurons from PINK1 mutation patients. The dimer consists of two monomers that are covalently linked by a disulfide bridge. In this conformation CISD1 cannot coordinate the iron-sulfur cofactor. Overexpressing Cisd, the Drosophila ortholog of CISD1, and a mutant Cisd incapable of binding the iron-sulfur cluster in Drosophila reduced climbing ability and lifespan. This was more pronounced with mutant Cisd and aggravated in Pink1 mutant flies. Complete loss of Cisd, in contrast, rescued all detrimental effects of Pink1 mutation on climbing ability, wing posture, dopamine levels, lifespan, and mitochondrial ultrastructure. Our results suggest that Cisd, probably iron-depleted Cisd, operates downstream of Pink1 shedding light on PD pathophysiology and implicating CISD1 as a potential therapeutic target.

Among the largest transcription factor families in plants, bZIPs are crucial for various developmental and physiological processes, particularly abiotic stress resistance. Setaria italica has become a model for understanding stress resistance mechanisms. In this study, we identified 90 bZIP transcription factors in the Setaria italica genome. SibZIPs were classified into 13 groups based on references to Arabidopsis bZIPs. Members in the same group shared similar motifs and gene structure pattern. In addition, gene duplication analysis indenfied 37 pairs of segmental duplicated genes and none tandem duplicated genes in S. italica suggesting segmental duplication contributed to the expansion of the S. italica bZIP gene family. Moreover, the number of SibZIPs genes (39) exhibiting higher expression in roots was significantly more than that in other organs. Twelve SibZIP genes were upregulated in response to dehydration stress. In conclusion, our study advances the current understanding of SibZIP genes and provide a number of candidates for functional analysis of drought tolerance in S. italica.

BackgroundThis study conducts a systematic review through meta-analysis, comparing the composition and diversity of the gut microbiome in patients with esophageal cancer and healthy individuals, and explores the relationship between risk factors and related factors of esophageal cancer.MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library. In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, Egger’s test, and Begg’s test to assess the risk of bias.ResultsIn this study, a total of 328 studies were identified through the literature search. Among them, 117 duplicate studies were removed, and 202 studies were excluded based on inclusion and exclusion criteria. Finally, 9 studies were included in the analysis, involving a total of 216 patients with esophageal carcinoma and 352 healthy controls. Four studies provided Chao1 index for quantitative consolidation (ES = 637.41, 95% CI: 549.16 to 725.66, p = 0.000, I2 = 98.2%). Two studies [27, 29] reported ACE index (ES = 438.89, 95% CI: 362.42 to 515.35, p = 0.000, I2 = 97%). Seven studies [26,27,29,30,32] reported the Shannon index for quantitative consolidation (ES = 4.38, 95% CI: 3.95 to 4.81, p = 0.000, I2 = 99%). At the phylum level, the abundance of Bacteroidetes(ES = 37.8, 95% CI: 25.75 to 49.85, p = 0.000, I2 = 87.2%) and Proteobacteria(ES = 7.48, 95% CI: 5.02 to 8.85, p = 0.04, I2 = 2.4%) have statistical difference between ESCC and HC. There was no significant difference between ESCC and HC in the abundance of genera(p>0.05).ConclusionsThis observational meta-analysis revealed that changes in the GM were correlated with esophageal carcinoma, and variations in some advantageous GM might involve regional differences. Additionally, the study aims to facilitate early diagnosis of esophageal cancer and improve screening and diagnostic efficiency.

When multiple CCHP microgrids are integrated into an active distribution network (ADN), the microgrids and the distribution network serve as distinct stakeholders, making the economic optimal dispatch of the system more complex. This paper proposes a distributed dispatch model of ADN with CCHP multi-microgrid, and refines the objective functions of each region. The analytical target cascading approach (ATC) is employed to model the power transaction as virtual sources/loads, and solve the optimal dispatch in parallel. Case studies demonstrate the proposed distributed model is capable of achieving economic optimization for both stakeholders.

With a significant increase in the obesity epidemic in China, addressing adolescent obesity should be highlighted as a priority. The current qualitative study aims to explore the perspectives of key stakeholders regarding adolescent obesity, providing guidance for developing effective obesity interventions for Chinese adolescents. A total of 12 focus group discussions were convened with a range of representative stakeholders including adolescents (n = 37), parents (n = 28), and school staff (n = 21) from sample schools. Semi-structured topic guides were used for data collection. All data were transcribed verbatim and analyzed thematically. From multiple stakeholder perspectives, we finally identified 3 overarching themes ( Understanding adolescent obesity, Key healthy lifestyles, and Barriers to obesity prevention practices ) and 8 sub-themes. While participants had mixed perceptions of status and prevalence of adolescent obesity, all acknowledged the serious health consequences associated with it. As significant modifiable risk factors, unhealthy diet and physical activity were identified to be prevalent among Chinese teenagers and lead to excessive weight gain. However, a variety of individual, environmental and sociocultural factors hindered the implementation of healthy lifestyles, affecting adolescent obesity prevention and control. Given adolescent obesity is a complex, multifactorial and multilevel public issue, comprehensive lifestyle interventions are recommended that synergistically engage multiple stakeholders across key communities to fight the ongoing obesity epidemic.

Introduction:Gan–jiang–ling–zhu (GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating yang, activating qi and dissipating dampness, GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated.Methods: NASH was induced in mice, followed by treatment with GJLZ decoction. Various methods including hematoxylin-eosin, oil red O staining, and triglyceride analysis were employed to evaluate the treatment effects of GJLZ decoction on NASH. Gut microbiota, metabolomics, cell viability assays, immunofluorescence and Western blotting were performed to unveil the mechanism behind GJLZ decoction.Results: GJLZ decoction treatment significantly improved hepatic steatosis in mice with NASH. It led to remodeling of gut flora and metabolite structures, including the 12-tridecenoic acid level. 12-Tridecenoic acid aggravated hepatic steatosis by promoting acetyl-coenzyme A carboxylase alpha (ACC) expression and inhibiting carnitine palmitoyltransferase 1A (CPT1A) expression. GJLZ decoction treatment reduced the 12-tridecenoic acid level, inhibited ACC activity and promoted CPT1A expression.Conclusion: Our results demonstrated that 12-tridecenoic acid aggravated hepatic steatosis by affecting the ACC–CPT1A axis and GJLZ decoction treatment effectively reduced the 12-tridecenoic acid level and improved steatosis.

BackgroundHepatocellular carcinoma (HCC) is the most common primary liver cancer and often arises in the context of chronic liver disease, such as hepatitis B or C infection, and cirrhosis. Advanced unresectable HCC (uHCC) presents significant treatment challenges due to its advanced stage and inoperability. One efficient treatment method for advanced uHCC is the use of hepatic arterial infusion chemotherapy (HAIC) combined with transcatheter arterial embolization (TAE).Patients and MethodsIn this study, we conducted a retrospective collection of clinical data, including basic information, radiological data, and blood test parameters, for patients with advanced uHCC who underwent TAE + HAIC treatment from August 2020 to February 2023. A total of 743 cases involving 262 patients were included. Ultimately, the covariates included in the analysis were the Child-Pugh score, extrahepatic metastasis, tumor number, tumor size, and treatment method.ResultsIn the study, we performed univariable and multivariable analysis on 23 clinical factors that were screened by LASSO regression, indicating that the five variables aforementionedly were identified as independent factors influencing patient prognosis. Then we developed a nomogram of the sensitive model and calculated concordance indices of prognostic survival models.ConclusionBased on the uHCC patient cohort, we have developed a prognostic model for OS in patients who received TAE + HAIC treatment. This model can accurately predict OS and has the potential to assist in personalized clinical decision-making.

According to the hypothesis that strange quark matter may be the true ground state of matter at extremely high densities, strange quark stars should be stable and could exist in the Universe. It is possible that pulsars may actually be strange stars, but not neutron stars. Here we present a short review on recent progresses in the field of strange quark stars. First, three popular phenomenological models widely used to describe strange quark matter are introduced, with special attention being paid on the corresponding equation of state in each model. Combining the equation of state with the Tolman-Oppenheimer-Volkov equations, the inner structure and mass-radius relation can be obtained for the whole sequence of strange stars. Tidal deformability and oscillations (both radial and non-radial oscillations), which are sensitive to the composition and the equations of state, are then described. Hybrid stars as a special kind of quark stars are discussed. Several other interesting aspects of strange stars are also included. For example, strong gravitational wave emissions may be generated by strange stars through various mechanisms, which may help identify strange stars via observations. Especially, close-in strange quark planets with respect to their hosts may provide a unique test for the existence of strange quark objects. Fierce electromagnetic bursts could also be generated by strange stars. The energy may come from the phase transition of neutron stars to strange stars, or from the merger of binary strange stars. The collapse of the strange star crust can also release a huge amount of energy. It is shown that strange quark stars may be involved in short gamma-ray bursts and fast radio bursts.

Objective Current biomarkers for predicting immunotherapy response in non-small-cell lung cancer (NSCLC) are derived from invasive procedures with limited predictive accuracy. Thus, identifying a non-invasive predictive biomarker would improve patient stratification and precision immunotherapy.Methods and analysis In this retrospective multicohort study, the discovery cohort included 205 NSCLC patients screened from ORIENT-11 and an external validation (EV) cohort included 99 real-world NSCLC patients. The ‘onion-mode segmentation’ method was developed to extract ‘onion-mode perfusion’ (OMP) from contrast-enhanced CT images. The predictive performance of OMP or its combination with the PD-L1 Tumour Proportion Score (TPS) was evaluated by the area under the curve (AUC).Results High baseline OMP was associated with significantly longer survival and predicted patient response to combination anti-PD-(L)1 therapy in the discovery and EV cohorts. OMP complemented the PD-L1 TPS with superior predictive sensitivity (p=0.02). In the PD-L1 TPS

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.

Ethnopharmacological relevanceDanggui Buxue decoction (DBD) is a traditional Chinese herbal formula. According to the theory of traditional Chinese medicine, the combination of Astragali Radix (AR) and Angelica sinensis (AS) is a classic prescription of tonifying qi and enriching blood. DBD has the functions of hematopoietic, immune enhancement and inflammation inhibition, usually used to treat qi and blood deficiency symptoms.Aim of the studyCyclophosphamide (CY) can inhibit humoral and cellular immunity, leading to the overall immune disorder of the body, resulting in immunosuppressive (IS). Pre-laboratory studies confirmed the immunomodulatory effects of DBD, but its mechanisms have not been thoroughly studied. In this study, the main purpose was to determine the effects of DBD on the immune function and intestinal mucosal barrier function of IS mice induced by CY, and initially explored the immunomodulatory mechanism of DBD.Materials and methods100 g of AR and 20 g of AS were accurately weighed and 0.5 g/mL of the DBD was obtained by boiling, filtration and rotary evaporation. Then, mice in the DBD group were administered 5 g/kg of DBD by gavage, positive group were administered 40 mg/kg of levamisole hydrochloride, whereas those in the control and model groups were given the corresponding volume of normal saline by gavage for 1 week. At the end of the experiment, blood, spleen, thymus, ileum and cecum contents of all the experimental mice were collected aseptically. IS mouse model induced by intraperitoneal injection of 80 mg/kg CY for three consecutive days. Pathomorphology was used to observe the physical barrier of the intestine, flow cytometry to detect splenic lymphocytes, immunohistochemistry to determine the content of intestinal barrier-associated proteins, ELISA to measure the secretion of ileal SIgA, qRT-PCR to detect the mRNA expression of immune-related genes in the intestine, and high-throughput sequencing and analysis of cecum contents.ResultsDBD alleviated spleen tissue damage and restored impaired immune functions, such as increased thymus index and CD4+/CD8+ subsets of spleen lymphocytes. In addition, DBD could increase ileum villi length and the ratio of villi length to crypt depth (V/C), and decrease crypt depth. Moreover, DBD administration up-regulated the expression of ZO-1, Occludin, Claudin-1, MUC-2 mRNA in ileum. And the secretions of sIgA and ZO-1 in ileum were also significantly improved. Furthermore, the administration of DBD can increase the diversity of gut microbiota, improve the composition of intestinal flora and increase the relative abundance of beneficial genus, such as Bacteroides.ConclusionDBD alleviated CY-induced immune damage by decreasing the ratio of spleen index to CD4+/CD8+ of T lymphocyte subsets. And the intestinal barrier function of mice was by improves improving the intestinal morphology of the ileum and up-regulating the expression levels of ZO-1, MUC-2 and SIgA. DBD regulates CY-induced gut microbiota dysregulation in mice by increasing species diversity and richness, regulating the phylum, class and order levels of Bacteroidetes.

Abstract BackgroundAdverse social determinants of health (SDoH) have been associated with cardiometabolic disease; however, disparities in cardiometabolic outcomes are rarely the result of a single risk factor. ObjectiveThis study aimed to identify and characterize SDoH phenotypes based on patient-reported and neighborhood-level data from the institutional electronic medical record and evaluate the prevalence of diabetes, obesity, and other cardiometabolic diseases by phenotype status. MethodsPatient-reported SDoH were collected (January to December 2020) and neighborhood-level social vulnerability, neighborhood socioeconomic status, and rurality were linked via census tract to geocoded patient addresses. Diabetes status was coded in the electronic medical record using International Classification of Diseases2 ResultsComplete data were available for analysis for 2380 patients (mean age 53, SD 16 years; n=1405, 59% female; n=1198, 50% non-White). Roughly 8% (n=179) reported housing insecurity, 30% (n=710) reported resource needs (food, health care, or utilities), and 49% (n=1158) lived in a high-vulnerability census tract. We identified 3 patient SDoH phenotypes: (1) high social risk, defined largely by self-reported SDoH (n=217, 9%); (2) adverse neighborhood SDoH (n=1353, 56%), defined largely by adverse neighborhood-level measures; and (3) low social risk (n=810, 34%), defined as low individual- and neighborhood-level risks. Patients with an adverse neighborhood SDoH phenotype had higher prevalence of diagnosed type 2 diabetes (PR 1.19, 95% CI 1.06‐1.33), hypertension (PR 1.14, 95% CI 1.02‐1.27), peripheral vascular disease (PR 1.46, 95% CI 1.09‐1.97), and heart failure (PR 1.46, 95% CI 1.20‐1.79). ConclusionsPatients with the adverse neighborhood SDoH phenotype had higher prevalence of poor cardiometabolic conditions compared to phenotypes determined by individual-level characteristics, suggesting that neighborhood environment plays a role, even if individual measures of socioeconomic status are not suboptimal.

ObjectivesAn increasing number of studies have shown that third (CB3)- and fourth-generation cryoballoons (CB4) have been used to treat various types of atrial fibrillation (AF), but previous research regarding the safety and efficacy of CB3 or CB4 ablation remains controversial. Therefore, a meta-analysis was performed to further evaluate the safety and efficacy of pulmonary vein isolation (PVI) using the CB3 and CB4 in the treatment of AF.MethodsWe searched PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Clinicaltrials.gov up to December 2023 for qualified trials and data extraction according to inclusion and exclusion criteria. All analyses were carried out using Review Manager 5.3 software.ResultsThe meta-analysis included 13 observational studies consisting of 3,281 subjects and did not include a randomized controlled trial. Overall analyses indicated that the CB3 significantly reduced total procedure time [weighted mean difference (WMD) = −8.69 min, 95% confidence interval (CI) = −15.45 to −1.94 min, I2 = 93%], increased the PVI recording [relative risk (RR) = 1.24, 95% CI = 1.03–1.49, I2 = 90%], and increased the mean nadir temperature of overall PVs (WMD = 2.80°C, 95% CI = 1.08–4.51°C, I2 = 89%) compared with the CB2. Moreover, the CB4 significantly reduced the total procedure time (WMD = −14.50 min, 95% CI = −20.89 to −8.11 min, I2 = 95%), reduced the fluoroscopy time (WMD = −2.37 min, 95% CI = −4.28 to −0.46 min, I2 = 95%), increased the PVI recording (RR = 1.40, 95% CI = 1.15–1.71, I2 = 90%) compared with the CB2. Time-to-isolation, the success rate of PVI, AF recurrence, and complications in the CB3 and CB4 were not significantly different compared with the CB2.ConclusionThese findings demonstrated that the CB3 and CB4 tended to be more effective than the CB2 in the treatment of AF, with shorter procedure times, more PVI recording, and similar safety endpoints.

Introduction Approximately, 50% of stroke survivors experience impaired walking ability 6 months after conventional rehabilitation and standard care. However, compared with upper limb motor function, research on lower limbs rehabilitation through non-invasive neuromodulation like repetitive transcranial magnetic stimulation (rTMS) has received less attention. Limited evidence exists regarding the effectiveness of intermittent theta-burst stimulation (iTBS), an optimised rTMS modality, on lower limbs rehabilitation after stroke. This study aims to evaluate the effects of iTBS on gait, balance and lower limbs motor function in stroke recovery while also exploring the underlying neural mechanisms using longitudinal analysis of multimodal neuroimaging data.Methods and analysis In this double-blinded randomised controlled trial, a total of 46 patients who had a stroke will be randomly assigned in a 1:1 ratio to receive either 15 sessions of leg motor area iTBS consisting of 600 pulses or sham stimulation over the course of 3 weeks. Additionally, conventional rehabilitation therapy will be administered following the (sham) iTBS intervention. The primary outcome measure will be the 10 m walking test. Secondary outcomes include the Fugl-Meyer assessment of the lower extremity, Timed Up and Go Test, Functional Ambulation Category Scale, Berg Balance Scale, modified Barthel Index, Mini-Mental State Examination, montreal cognitive assessment, tecnobody balance assessment encompassing both static and dynamic stability evaluations, surface electromyography recording muscle activation of the lower limbs, three-dimensional gait analysis focusing on temporal and spatial parameters as well as ground reaction force measurements, corticomotor excitability tests including resting motor threshold, motor evoked potential and recruitment curves and multimodal functional MRI scanning. Outcome measures will be collected prior to and after the intervention period with follow-up at 3 weeks.Ethics and dissemination The study has received approval from the Medical Research Ethics Committee of Wuxi Mental Health Center/Wuxi Central Rehabilitation Hospital (no. WXMHCCIRB2023LLky078). Results will be disseminated through peer-reviewed journals and scientific conferences.Trial registration number ChiCTR2300077431.