Search

Background: The dead space fraction (VD/VT) has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome (ARDS). However, its measurement relies on expired carbon dioxide, limiting its widespread application in clinical practice. Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT. In this study, we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation. Methods: This retrospective observational study was conducted using data from the Chinese database in intensive care (CDIC). Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021. We collected data during the first 7 days of ventilation to calculate various dead space estimates, including ventilatory ratio (VR), corrected minute ventilation (V˙Ecorr), VD/VT (Harris–Benedict), VD/VT (Siddiki estimate), and VD/VT (Penn State estimate) longitudinally. A time-dependent Cox model was used to handle these time-varying estimates. Results: A total of 392 patients (median age 66 [interquartile range: 55–77] years, median SOFA score 9 [interquartile range: 7–12]) were finally included in our analysis, among whom 132 (33.7%) patients died within 28 days of admission. VR (hazard ratio [HR]=1.04 per 0.1 increase, 95% confidence interval [CI]: 1.01 to 1.06; P=0.013), V˙Ecorr (HR=1.08 per 1 increase, 95% CI: 1.04 to 1.12; P < 0.001), VD/VT (Harris–Benedict) (HR=1.25 per 0.1 increase, 95% CI: 1.06 to 1.47; P=0.006), and VD/VT (Penn State estimate) (HR=1.22 per 0.1 increase, 95% CI: 1.04 to 1.44; P=0.017) remained significant after adjustment, while VD/VT (Siddiki estimate) (HR=1.10 per 0.1 increase, 95% CI: 1.00 to 1.20; P=0.058) did not. Given a large number of negative values, VD/VT (Siddiki estimate) and VD/VT (Penn State estimate) were not recommended as reliable substitutes. Long-term exposure to VR >1.3, V˙Ecorr >7.53, and VD/VT (Harris–Benedict) >0.59 was independently associated with an increased risk of mortality in ARDS patients. These findings were validated in the fluid and catheter treatment trial (FACTT) database. Conclusions: In cases where VD/VT cannot be measured directly, early time-varying estimates of VD/VT such as VR, V˙Ecorr, and VD/VT (Harris–Benedict) can be considered for predicting mortality in ARDS patients, offering a rapid bedside application.

Abstract Background A triplet chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) is used to treat head and neck squamous cell carcinoma; however, it is toxic to bone marrow mesenchymal stem cells (BMSCs). We previously demonstrated that Ganoderma spore lipid (GSL) protect BMSCs against cyclophosphamide toxicity. In this study, we investigated the protective effects of GSL against TPF-induced BMSCs and hematopoietic damage. Methods BMSCs and C57BL/6 mice were divided into control, TPF, co-treatment (simultaneously treated with GSL and TPF for 2 days), and pre-treatment (treated with GSL for 7 days before 2 days of TPF treatment) groups. In vitro, morphology, phenotype, proliferation, senescence, apoptosis, reactive oxygen species (ROS), and differentiation of BMSCs were evaluated. In vivo, peripheral platelets (PLTs) and white blood cells (WBCs) from mouse venous blood were quantified. Bone marrow cells were isolated for hematopoietic colony-forming examination. Results In vitro, GSL significantly alleviated TPF-induced damage to BMSCs compared with the TPF group, recovering their morphology, phenotype, proliferation, and differentiation capacity (p

Abstract It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.

Abstract Mesenchymal stem cells (MSCs) are widely distributed pluripotent stem cells with powerful immunomodulatory capacity. MSCs transplantation therapy (MSCT) is widely used in the fields of tissue regeneration and repair, and treatment of inflammatory diseases. Apoptosis is an important way for tissues to maintain cell renewal, but it also plays an important role in various diseases. And many studies have shown that MSCs improves the diseases by regulating cell apoptosis. The regulation of MSCs on apoptosis is double-sided. On the one hand, MSCs significantly inhibit the apoptosis of diseased cells. On the other hand, MSCs also promote the apoptosis of tumor cells and excessive immune cells. Furthermore, MSCs regulate apoptosis through multiple molecules and pathways, including three classical apoptotic signaling pathways and other pathways. In this review, we summarize the current evidence on the regulation of apoptosis by MSCs.

Abstract Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein‐Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV‐ (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC‐associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene‐edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV‐coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV‐ and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

PurposeWhile strengthening exercises are recommended for knee osteoarthritis (KOA) treatment, the optimal type of muscle contraction remains unclear, with current research showing conflicting results. This network meta-analysis (NMA) aims to evaluate the efficacy of lower limb strengthening exercises based on different muscle contraction characteristics for KOA patients and provide clinical references.MethodsWe conducted the NMA following the PRISMA-NMA. A comprehensive search of five databases (PubMed, Web of Science, CENTRAL, Embase, and SPORTDiscus) up to August 2024 identified randomized controlled trials (RCTs) investigating lower limb strengthening exercises in KOA patients. Control groups included receiving usual care, only providing health education, or no intervention at all. Outcomes analyzed included pain, physical function, quality of life, and muscle strength.ResultsForty-one studies (2,251 participants) were included. Twenty-eight studies used rigorous randomization; eighteen reported allocation concealment. All had high performance bias risk due to exercise interventions. Regarding efficacy, isokinetic exercise ranked highest in pain relief (SMD = 0.70, 95% CI: 0.50–0.91, SUCRA = 82.6%), function improvement (SMD = 0.75, 95% CI: 0.57–0.92, SUCRA = 96.1%), and enhancement in muscle strength (SMD = 0.56, 95% CI: 0.34–0.78, SUCRA = 90.1%). Isometric exercise ranked highest in improving quality of life (SMD = 0.80, 95% CI: 0.28–1.31, SUCRA = 90.5%). Mixed strengthening exercise ranked lowest across all outcomes. High-frequency interventions (≥5 times/week) showed superior pain relief compared with low-frequency (≤3 times/week) for isotonic, isometric, and isokinetic exercise.ConclusionThis NMA suggests isokinetic exercise may be most effective for pain, function, and muscle strength in KOA patients, while isometric exercise benefits quality of life most. Mixed strengthening exercise ranked lowest across all outcomes. High-frequency interventions appear more effective than low-frequency ones. These findings support personalized KOA treatment, considering efficacy, accessibility, and patient-specific factors. Study biases, heterogeneity, and other limitations may affect result reliability. Future research should focus on high-quality studies with standardized protocols and analyze dose–response relationships to refine KOA treatment strategies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024582525, identifier: CRD42024582525.

ObjectiveThe goal of this study is to assess the clinical attributes exhibited by patients aged 85 years and older who present different manifestations of COVID-19, and to examine the factors influencing the classification of the disease severity.MethodThis retrospective study was conducted at a single center, encompassing an analysis of clinical data obtained from patients with COVID-19 admitted to a general geriatric hospital in Hangzhou, Zhejiang, China, during the period from December 20, 2022, to February 1, 2023. The study focused on 91 eligible patients whose disease severity was compared based on the imaging findings.ResultsA total of 91 patients aged 85 years and older, with a median age of 92, including 46 males, 10 exhibiting mild symptoms, 48 moderate cases, and 33 severe cases met the inclusion criteria. Notably, disease severity displayed a significant correlation with age (p

Background: The extensive community of gut microbiota significantly influences various biological functions throughout the body, making its characterization a focal point in biomedicine research. Over the past few decades, studies have revealed a potential link between specific gut bacteria, their associated metabolic pathways, and influenza. Bacterial metabolites can communicate directly or indirectly with organs beyond the gut via the intestinal barrier, thereby impacting the physiological functions of the host. As the microbiota increasingly emerges as a ‘gut signature’ in influenza, gaining a deeper understanding of its role may offer new insights into its pathophysiological relevance and open avenues for novel therapeutic targets. In this Review, we explore the differences in gut microbiota between healthy individuals and those with influenza, the relationship between gut microbiota metabolites and influenza, and potential strategies for preventing and treating influenza through the regulation of gut microbiota and its metabolites, including fecal microbiota transplantation and microecological preparations. Methods: We utilized PubMed and Web of Science as our search databases, employing keywords such as “influenza,” “gut microbiota,” “traditional Chinese medicine,” “metabolites,” “prebiotics,” “probiotics,” and “machine learning” to retrieve studies examining the potential therapeutic connections between the modulation of gut microbiota and its metabolites in the treatment of influenza. The search encompassed literature from the inception of the databases up to December 2023. Results: Fecal microbiota transplantation (FMT), microbial preparations (probiotics and prebiotics), and traditional Chinese medicine have unique advantages in regulating intestinal microbiota and its metabolites to improve influenza outcomes. The primary mechanism involves increasing beneficial intestinal bacteria such as Bacteroidetes and Bifidobacterium while reducing harmful bacteria such as Proteobacteria. These interventions act directly or indirectly on metabolites such as short-chain fatty acids (SCFAs), amino acids (AAs), bile acids, and monoamines to alleviate lung inflammation, reduce viral load, and exert anti-influenza virus effects. Conclusion: The gut microbiota and its metabolites have direct or indirect therapeutic effects on influenza, presenting broad research potential for providing new directions in influenza research and offering references for clinical prevention and treatment. Future research should focus on identifying key strains, specific metabolites, and immune regulation mechanisms within the gut microbiota to accurately target microbiota interventions and prevent respiratory viral infections such as influenza.

Background: Research underscores the significant influence of histone lactylation pathways in the progression of Alzheimer's disease (AD), though the molecular mechanisms associated with histone lactylation-related genes (HLRGs) in AD are still insufficiently investigated. Methods: This study employed datasets GSE85426 and GSE97760 to identify candidate genes by intersecting weighted gene co-expression network analysis (WGCNA) module genes with AD-control differentially expressed genes (DEGs). Subsequently, machine learning refined key genes, validated by receiver operating characteristic (ROC) curve performance. Gene-set enrichment analysis (GSEA) explored the molecular mechanisms of these diagnostic markers. Concurrently, the association between the diagnostic genes and both differential immune cells and immune responses was examined. Furthermore, a ceRNA and gene-drug network was developed. Finally, the expression of the selected genes was validated using brain tissues from AD model mice. Results: This study identified five genes (ARID5B, NSMCE4A, SESN1, THADA, and XPA) with significant diagnostic utility, primarily enriched in olfactory transduction and N-glycan biosynthesis pathways. Correlation analysis demonstrated a strong positive association between all diagnostic genes and naive B cells. The ceRNA regulatory network comprised 7 miRNAs, 2 mRNAs, and 25 lncRNAs. Additionally, 33 drugs targeting the diagnostic genes were predicted. Following expression validation through training and validation sets, three genes (ARID5B, SESN1, XPA) were ultimately confirmed as biomarkers for this study. RT-qPCR and Western blot analyses revealed upregulated expression of ARID5B, SESN1, and XPA in the cerebral tissue of AD model mice. Conclusion: Three histone lactylation-linked genes (ARID5B, SESN1, XPA) were identified as potential AD biomarkers, indicating a strong association with disease progression.

Rationale and objectives: To describe MRI characteristics of ureteral endometriosis (UE) in identifying intrinsic involvement of the ureteric wall and predicting complex procedures. Methods: Thirty-three UE lesions in 30 patients treated for UE over a 20-year period were reviewed. A systematic analysis of 13 MRI (ureteric wall thickening, circumference, T1 signal, T2 signal, ureterectasis, lateral parametrial endometriosis (LPE), rectal endometriosis, the foregoing three-characteristic diameter, ovarian endometriomas, adenomyosis, paraurethral endometriosis) and 5 clinical (age, BMI, CA125, creatinine and rAFS stage) characteristics was performed. MRI results were compared to histology and surgical procedure performed (simple versus complex ureteral procedures). Results: Twenty-five extrinsic and 8 intrinsic UE were pathologically identified. Twenty lesions underwent a simple procedure, and 12 underwent a complex procedure, with 1 ureteroscopic biopsy. There were significant differences in the characteristics of ureteric wall thickening, the diameter of dilated ureter and LPE, rectal endometriosis and adenomyosis between extrinsic and intrinsic UE (p

SAPHO syndrome is a complex inflammatory disorder affecting the skin and bones, characterized by osteomyelitis, acne, and pustulosis. Cytokines play a pivotal role in the pathogenesis of SAPHO syndrome, especially in inflammatory responses and immune regulation. This article reviews the cytokines involved in the pathogenesis of SAPHO syndrome, such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, IL-10, and transforming growth factor-β (TGF-β), and discusses their potential as intervention points for treatment. These findings elucidate the intricate immune regulatory network of SAPHO syndrome and provide a theoretical foundation for the development of new targeted therapeutic strategies.

Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, and there are no effective drug treatments. Low-intensity pulsed ultrasound (LIPUS) has garnered attention as a promising noninvasive neuromodulation method. In this study, we investigate its effects on the motor cortex and underlying mechanisms using the SOD1G93A mouse model of ALS. Our results show that LIPUS treatment delays disease onset and prolongs lifespan in ALS mice. LIPUS significantly increases cerebral blood flow in the motor cortex by preserving vascular endothelial cell integrity and increasing microvascular density, which may be mediated via the ion channel TRPV4. RNA sequencing analysis reveals that LIPUS substantially reduces the expression of genes associated with neuroinflammation. These findings suggest that LIPUS applied to the motor cortex may represent a potentially effective therapeutic tool for the treatment of ALS.

Environmental pollutants are considered as a cause of tumorigenesis, but approaches to assess their risk of causing tumors remain insufficient. As an alternative approach, the adverse outcome pathway (AOP) framework is used to assess the risk of tumors caused by environmental pollutants. Arsenic is a pollutant associated with lung cancer, but early assessment of lung cancer risk is lacking. Therefore, we applied the AOP framework to arsenic-induced lung cancer. A systematic review revealed increased risks of lung cancer following exposure to a range of arsenic concentrations in drinking water (OR = 1.83, 95 % CI = 1.46–2.30). We obtained, from public databases, genes related to risk of arsenic-induced lung cancer. Then, Cox and LASSO regressions were used to screen target genes from the risk genes. Subsequently, target genes, phenotypes, and pathways were used to construct the computational AOP network, which was determined by Cytoscape to have 156 edges and 45 nodes. Further, target genes, phenotypes, and pathways were used as molecular initiating events and key events to construct the AOP framework depending on upstream and downstream relationships. In the AOP framework, by Weight of Evidence, arsenic exposure increased levels of EGFR, activated the PI3K/AKT pathway, regulated cell proliferation by promoting the G1/S phase transition, and caused generation of lung cancers. External validation was achieved through arsenite-induced, malignant transformed human bronchial epithelial (HBE) cells. Overall, these results, by integration into existing data to construct an AOP framework, provide insights into the assessment of lung cancer risk for arsenic exposure. Special attention needs to be focused on populations with low-dose arsenic exposure.

The synergistic development of ecosystem services (ESs) and human well-being (HWB) is of utmost importance for the construction of sustainable development. In this study, we focus on the provinces of Qinghai and Tibet as our research area. To measure the value of ESs and HWB, we employ the per unit area value equivalence method and the Human Development Index method, respectively. Based on the feedback relationship between ESs and HWB, we establish a system dynamics model that considers economic, social, ecological, land use, and policy influencing factors. This model enables us to conduct multiscenario simulation predictions and system dynamics sensitivity analysis, aiming to explore the main factors driving the coupled relationship between ESs and HWB. The results show that: (1) From 2010 to 2020, the value of ESs in the Qinghai-Tibet Plateau generally increased, from 6049.49 billion CNY in 2010 to 6210.65 billion CNY in 2020, with generally higher in the southeast and lower in the northwest, and local high-high and high-low aggregation patterns. (2) From 2010 to 2020, the HWB index in the Qinghai-Tibet Plateau exhibited a continuous rise, from 0.19 in 2010 to 0.53 in 2020, indicating substantial development potential. (3) The system dynamics model established in this study demonstrates effectiveness with high fitting accuracy. From 2021 to 2050, the HWB index in the Qinghai-Tibet Plateau displays an upward trend in all five scenarios, while the value of ESs shows a declining trend under the economic development priority scenario and an upward trend under the status quo, ecological protection priority, social development priority, and integrated development scenarios. Among these, the integrated development scenario proves optimal as it satisfies economic development needs, basic social security, and environmental protection requirements. (4) Grasslands, water areas, and environmental protection investment are identified as the main driving factors in the synergistic improvement of ESs and HWB. And the influence of different driving factors will change dynamically with time. Our study can guide the search for the optimal development model for the synergistic improvement of ESs and HWB in the Qinghai-Tibet Plateau, providing a theoretical foundation for future development planning.

Copper is one of the predominant water pollutants. Excessive exposure to copper can cause harm to animal health, affecting the central nervous system and causing blood abnormalities. Cuproptosis is a novel form of cell death that differs from previous programmed cell death methods. However, the impact of copper on the intestines remains unclear. Therefore, we investigated the effects of different concentrations of copper exposure on the intestinal proteome of Takifugu rubripes (T. rubripes). Relevant biomarkers were used to detect cuproptosis. We revealed the crosstalk relationship between cuproptosis and self-rescue at different concentrations, and discussed the feasibility of using potential cuproptosis indicators as anti-infection factors. We observed intestinal damage in the three copper exposure groups, especially in T. rubripes treated with 100 and 500 μg/L copper, with shedding and breakage of intestinal villus and fuzzy and loose structure of intestinal mucosa. The presence of copper stress not only causes cuproptosis but also oxidative damage caused by reactive oxygen species (ROS). The results of quantitative proteomics by TMT showed that compared to the 50 and 100 μg/L copper exposure groups, the expression of glutaminase, pyruvate kinase, and skin mucus lectin in the 500 μg/L group was significantly increased. The positive mediators COX5A and CTNNB1, as well as the negative mediators CD4 and FDXR, were found to be differentially expressed. Using the protein expression trends of cuproptosis indicator factors FDX1 and DLAT to indicate the concentration of copper ions in the environment. In addition, we found a new effect of promoting ferroptosis: providing additional copper ions can activate the phenomenon of ferroptosis. Our results expand our understanding of the potential health risks of copper in T. rubripes. At the same time, it is of great significance for the process of copper poisoning and the development of new environmental toxicology detection reagents.

Abstract Background Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV‐related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)‐negative HBV‐related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. Methods This historical cohort study involved 1232 NA‐treated HBeAg‐negative patients who underwent curative hepatectomy for HBV‐related HCC from 2014 to 2019. The recurrence‐free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. Results Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348–3.109, p

Tigecycline is a last-resort drug used to treat serious infections caused by multidrug-resistant bacteria. tet(X4) is a recently discovered plasmid-mediated tigecycline resistance gene that confers high-level resistance to tigecycline and other tetracyclines. Since the first discovery of tet(X4) in 2019, it has spread rapidly worldwide, and as a consequence, tigecycline has become increasingly ineffective in the clinical treatment of multidrug-resistant infections. In this study, we identified and analyzed tet(X4)-positive Escherichia coli isolates from duck farms in Hunan Province, China. In total, 976 samples were collected from nine duck farms. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed to establish the phenotypes and genotypes of tet(X4)-positive isolates. In addition, the genomic characteristics and transferability of tet(X4) were determined based on bioinformatics analysis and conjugation. We accordingly detected an E. coli strain harboring tet(X4) and seven other resistance genes in duck feces. Multi-locus sequence typing analysis revealed that this isolate belonged to a new clone, and subsequent genetic analysis indicated that tet(X4) was carried in a 4608-bp circular intermediate, flanked by ISVsa3-ORF2-abh elements. Moreover, it exhibited transferability to E. coli C600 with a frequency of 10-5. The detection of tet(X4)-harboring E, coli strains on duck farms enhances our understanding of tigecycline resistance dynamics. The transferable nature of the circular intermediate of tet(X4) contributing to the spread of tigecycline resistance genes poses a substantial threat to healthcare. Consequently, vigilant monitoring and proactive measures are necessary to prevent their spread.

BackgroundPrenatal anxiety and depression exert a significant influence on the physiological and psychological health outcomes of both expectant mothers and their infants. The aim of this study was to explore the intrinsic relationships between maternal anxiety, depression in early pregnancy, and their influencing factors. The findings of this study provide scientific basis for developing targeted preventive interventions.MethodsThe study involved 887 expectant mothers in the early stages of pregnancy residing in Changsha City from March to August 2022. The sociodemographic characteristics, health and lifestyle factors, and pregnancy-related factors of participants were collected. The Edinburgh Postnatal Depression Scale and the Self-Rating Anxiety Scale were used to assess depression and anxiety, respectively. Chi-square tests and multivariate logistic regression models using SPSS 26.0 were used to assess factors impacting early pregnancy anxiety and depression. Amos 23.0 was used to construct a path model to determine the potential pathways of the influencing factors.ResultsIn early pregnancy, the prevalence of depression and anxiety were 17.4% and 15.8%, respectively. Path analysis showed that early pregnancy anxiety and illness during pregnancy had a direct effect on early pregnancy depression. Anxiety had the greatest overall impact on early pregnancy depression. Education, maternal comorbidities, symptoms of pregnancy, electronic device usage time, work stress, active smoking in the 6 months before pregnancy, and sleep quality were found to solely exert indirect effects on early pregnancy depression. Sleep quality had the greatest overall impact on early pregnancy anxiety. Active smoking in the 6 months before pregnancy, sleep quality, and work stress only had a direct impact on early pregnancy anxiety. Additionally, electronic device usage duration and monthly per capita household income exclusively indirectly impacted symptoms of early pregnancy anxiety.ConclusionThe study highlights the importance of targeted interventions in early screening. Avoiding excessive use of electronic devices and active smoking in the 6 months before pregnancy, alleviating work stress and symptoms of pregnancy, increasing education levels and monthly per capita household income, improving sleep quality, and actively preventing illnesses during pregnancy and maternal comorbidities might reduce anxiety and depression in early pregnancy.

IntroductionEndometriosis is delineated as a benign yet steroid-dependent disorder characterized by the ectopic presence of endometrial glandular and stromal cells outside the uterine cavity, affecting estimated 10%–15% of women of reproductive age, 20%–50% of all women with infertility and costing a great economic burden per-patient. Endometriosis exerts pervasive influence on multiple facets of female reproductive physiology. Given its characterization as a chronic inflammatory disorder, escalated levels of pro-inflammatory cytokines were unequivocally recognized as well-established characteristics of endometriosis, which might attribute to mechanisms like retrograde menstruation, progesterone receptor resistance, and immune dysregulation. Therapeutic utilization of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, analgesic agent for reducing pain, inflammation, and fever, could be holding promise in augmenting reproductive outcomes of endometriosis women. Therefore, the objective of this comprehensive review is to elucidate the intricate interplay between endometriosis and aspirin, both within the context of infertility and beyond. We meticulously explore potential pharmacological agents targeting endometriosis, which may concurrently optimize the efficacy of reproductive interventions, while also delving into the underlying mechanistic pathways linking endometriosis with inflammatory processes.MethodsWe conducted a comprehensive search in the data available in PubMed and the Web of Science using the terms ‘endometriosis’ and ‘aspirin’. Then analyzed the identified articles based on established inclusion and exclusion criteria independently by three reviewers.ResultsThe survey of the chosen terms revealed 72 articles, only 10 of which were considered for review.DiscussionBased on the research available currently, it is not substantial enough to address the conclusion that aspirin shall be an effective therapeutic choice for endometriosis, further studies are needed to elucidate the efficacy, safety profile, and optimal dosing regimens of aspirin in the context of endometriosis treatment.

Vibration control is extremely important for countless mechanical systems. Inerter is a two-terminal dynamic element proposed in 2002, based on analogy between mechanical system and electric system. Dynamic characteristic of an ideal inerter is pure inertia. Force applied on each terminal of an inerter is directly proportional to relative acceleration of two terminals. Since inerter was put forward, it has made significant progress in vibration control systems. The paper is a review about physical realizations of inerter as well as inerter-based vibration control. Physical realizations and applications in vibration control of inerter are focused. First, the develop of inerter and typical physical realizations of inerter are introduced. The normative derivation processes based on Lagrange equation method of the dynamic relationships in the different inerters are summarized. And then, three categories of common inerter-based vibration control systems are explained. Finally, research trend of physical realizations of inerter are summarized, and the possible researches on inerter-based vibration control are discussed.

Abstract The factors driving glioma progression remain poorly understood. Here, the epigenetic regulator TRIM24 is identified as a driver of glioma progression, where TRIM24 overexpression promotes HRasV12 anaplastic astrocytoma (AA) progression into epithelioid GBM (Ep‐GBM)‐like tumors. Co‐transfection of TRIM24 with HRasV12 also induces Ep‐GBM‐like transformation of human neural stem cells (hNSCs) with tumor protein p53 gene (TP53) knockdown. Furthermore, TRIM24 is highly expressed in clinical Ep‐GBM specimens. Using single‐cell RNA‐sequencing (scRNA‐Seq), the authors show that TRIM24 overexpression impacts both intratumoral heterogeneity and the tumor microenvironment. Mechanically, HRasV12 activates phosphorylated adaptor for RNA export (PHAX) and upregulates U3 small nucleolar RNAs (U3 snoRNAs) to recruit Ku‐dependent DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs). Overexpressed TRIM24 is also recruited by PHAX to U3 snoRNAs, thereby facilitating DNA‐PKcs phosphorylation of TRIM24 at S767/768 residues. Phosphorylated TRIM24 induces epigenome and transcription factor network reprogramming and promotes Ep‐GBM‐like transformation. Targeting DNA‐PKcs with the small molecule inhibitor NU7441 synergizes with temozolomide to reduce Ep‐GBM tumorigenicity and prolong animal survival. These findings provide new insights into the epigenetic regulation of Ep‐GBM‐like transformation and suggest a potential therapeutic strategy for patients with Ep‐GBM.

Background Beat‐to‐beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure‐receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat‐to‐beat BPV within 24 hours of acute ischemic stroke onset. Methods and Results This study prospectively monitored beat‐to‐beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat‐to‐beat BPV, heart rate variability, and the cross‐correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat‐to‐beat BPV to the traditional model for predicting prognosis. Beat‐to‐beat BPV increased significantly in the unfavorable outcome group (P0.05). Furthermore, beat‐to‐beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P

ObjectiveFew comparisons have been implemented between different prenatal care utilization indices and their effects on adverse outcomes. This study investigated the appropriateness of Chinese antenatal care (ANC) regulations and compared Chinese and American adequacy of prenatal care utilization (APNCU) scores.MethodsFrom 2010 to 2022, the medical records of 60,114 pregnant women were collected from the electronic medical record system (EMRS) in Zhoushan, China. ANC utilization was measured using the APNCU score and five times antenatal care (ANC5). Birth weight outcomes, including small for gestational age (SGA) and large for gestational age (LGA), low birth weight (LBW), macrosomia, birth weight, and preterm birth (PTB), were utilized as outcomes. Multinomial, linear, and logistic regression were used to analyze the association of ANC5 and APNCU with outcomes, respectively. Crossover analysis was implemented to compare the interaction between ANC5 and APNCU on the outcomes.ResultsWomen who received inadequate prenatal care had increased odds for PTB (ANC5: odds ratio (OR) = 1.12, 95% confidence interval (95%CI) = 1.03–1.21; APNCU: OR = 1.18, 95%CI: 1.07–1.29), delivering SGA infants (ANC5: OR = 1.13, 95%CI = 1.07–1.21; APNCU: OR = 1.11, 95%CI = 1.03–1.20). Crossover analysis revealed that inadequate prenatal care in APNCU only was significantly associated with an increased risk of PTB (OR = 1.48, 95%CI: 1.26–1.73).ConclusionWomen with inadequate prenatal care in ANC5 or APNCU were more likely to suffer from adverse birth outcomes, including PTB, birth weight loss, SGA, and LBW. It indicated that adequate prenatal care is necessary for pregnant women. However, there were interactions between ANC5 and APNCU on PTB, with inadequate prenatal care use by APNCU showing the highest risk of PTB. This indicates that APNCU would be a better tool for evaluating prenatal care use.

Ginseng, the dried root of Panax ginseng C.A. Mey., is widely used in Chinese herbal medicine. Ginsenosides, the primary active components of ginseng, exhibit diverse anticancer functions through various mechanisms, such as inhibiting tumor cell proliferation, promoting apoptosis, and suppressing cell invasion and migration. In this article, the mechanism of action of 20 ginsenoside subtypes in tumor therapy and the research progress of multifunctional nanosystems are reviewed, in order to provide reference for clinical prevention and treatment of cancer.

Corn-soybean rotation is a cropping pattern to optimize crop structure and improve resource use efficiency, and nitrogen (N) fertilizer application is an indispensable tool to increase corn yields. However, the effects of N fertilizer application levels on corn yield and soil N storage under corn-soybean rotation have not been systematically studied. The experimental located in the central part of the Songnen Plain, a split-zone experimental design was used with two planting patterns of continuous corn (CC) and corn-soybean rotations (RC) in the main zone and three N application rates of 0, 180, and 360 kg hm-2 of urea in the secondary zone. The research has shown that RC treatments can enhance plant growth and increase corn yield by 4.76% to 79.92% compared to CC treatments. The amount of N fertilizer applied has a negative correlation with yield increase range, and N application above 180 kg hm-2 has a significantly lower effect on corn yield increase. Therefore, a reduction in N fertilizer application may be appropriate. RC increased soil N storage by improving soil N-transforming enzyme activity, improving soil N content and the proportion of soil organic N fractions. Additionally, it can improve plant N use efficiency by 1.4%-5.6%. Soybeans grown in corn-soybean rotations systems have the potential to replace more than 180 kg hm-2 of urea application. Corn-soybean rotation with low N inputs is an efficient and sustainable agricultural strategy.

Abstract Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one‐third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end‐stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

BackgroundPlatycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5'AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease.MethodsClean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10 mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake in vitro. In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids.ResultsPD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice.ConclusionPD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption.

One of the fundamental processes in nuclear physics is nuclear excitation by electron capture (NEEC). Having been proposed theoretically for almost 50 years, the experimental confirmation of NEEC is still missing, making it imperative to validate this process. In this paper, we propose a new experimental method based on the anti-coincidence principle to search for the long-anticipated NEEC phenomenon, which involve heavy-ion storage rings. Our calculations indicate that the proposed experimental setup, storage ring, have the potential to surmount background noise, particularly Radiative Recombination (RR) and Coulomb Excitation (CE), and offer a high likelihood of discovering the long-awaited NEEC process.

Abstract Understanding soil moisture variability and estimating high‐resolution soil moisture at subfield to field scales is critical for agricultural research and applications. However, systematic investigation of subfield scale soil moisture variability over cropland is still lacking from both measurement and satellite remote sensing. In this study, we aim to investigate (1) the characteristics of within‐field soil moisture distribution over typical cropland in the US Midwest and (2) the capabilities of satellite remote sensing in capturing the spatiotemporal variabilities of soil moisture at subfield scale. Specifically, we conducted soil moisture field experiments in three typical commercial agricultural fields (∼85 acres per field) in central Illinois, representing typical commercial farmlands in the US Midwest, and compared the soil moisture measurements with satellite remote sensing data from optical and active microwave sensors. In each field, dense soil moisture samples (spaced at 50–60 m) were obtained for two dry down events in May and July 2021, and multiple long‐term soil moisture stations were installed. We found prominent time‐invariant spatial structures of soil moisture at within‐field scales both during the dry down period and over longer time scales, and the stability is minimally affected by plant water use during the growing season. Comparing the field campaign measurements with satellite remote sensing data, we found that surface reflectance of shortwave infrared bands, such as SWIR1 (1610 nm) from Sentinel‐2, can capture relative surface soil moisture patterns at within‐field scales, but their relationships with soil moisture are field specific. These findings and the improved understanding of within‐field soil moisture dynamics could potentially help future research on high‐resolution soil moisture estimation with multi‐source remote sensing data.

PurposeTo evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT)MethodsThis retrospective study included patients who received mFOLFOX-based HAIC combined with TKIs and ICIs from January 2021 to January 2023. The primary outcome was the objective response rate of PVTT response, and the secondary outcomes were 6-month, 1-year survival rate, overall survival (OS), and corresponding adverse events and complications were also evaluated. PVTT responses were assessed using ITK-SNAP software.ResultsA total of 37 patients were included in the analysis, 18.92% achieved a complete response and 56.76% achieved a partial response in PVTT response. The objective response rate (ORR) of PVTT was 75.68%. The 6-month survival rate was 89%, the 1-year survival rate was 66%, and the median OS was 15.8 months. In univariate analysis, Child-Pugh score (P=0.010) was important factor for predicting OS; in multivariate analysis, Child-Pugh score (P=0.015, HR= 3.089, 95%CI: 1.250–7.633) was the important factor for predicting OS. In terms of adverse reactions, the most common adverse reactions associated with HAIC are pain and thrombocytopenia associated with oxaliplatin.ConclusionFOLFOX-based HAIC combined with TKIs and ICIs induced an objective response rate of 75.68% in PVTT.Clinical signicanceFOLFOX-based HAIC combined with TKIs and ICIs provides more treatment options for PVTT.

BackgroundThe latest published therapeutic drug monitoring (TDM) guidelines for vancomycin recommend changing trough-based monitoring to area under the concentration-to-time curve (AUC)-based monitoring. This study aimed to evaluate the implementation status and perceptions of vancomycin AUC-based TDM in China and to determine the challenges in performing AUC-based TDM.MethodsA nationwide cross-sectional survey was conducted in China using an online questionnaire. The questionnaire comprised a total of 25 questions with open- and closed-ended answers to collect information about the current implementation of vancomycin TDM and the participants’ perceptions of these practices. The questionnaire responses were collected via the Questionnaire Star platform and analyzed.ResultsA total of 161 questionnaires were completed by 131 hospitals and were included. Approximately 59.5% (78/131) of the surveyed hospitals conducted vancomycin TDM; however, only 10.7% (14/131) of these hospitals performed AUC-based vancomycin TDM. Of the eligible participants, 58.4% (94/161) had experience with vancomycin TDM, and only 37 participants (37/161, 23.0%) had the ability to estimate the AUC, primarily through Bayesian simulation (33/161, 20.5%). The participants considered the following challenges to implementing AUC-based monitoring: (1) the high cost of AUC-based monitoring; (2) inadequate knowledge among pharmacists and/or physicians; (3) the complexity of AUC calculations; (4) difficulty obtaining AUC software; and (5) unclear benefit of AUC-based monitoring.ConclusionThe majority of surveyed hospitals have not yet implemented AUC-based vancomycin TDM. Multiple challenges should be addressed before wide implementation of AUC-based monitoring, and guidance for trough-based monitoring is still needed.

Background: Job burnout is a worldwide public health problem that has rarely been addressed among rural medical staff, particularly in county-level hospitals. Hence, we conducted a bibliometric study to gain global insights and research trends and a cross-sectional study to assess the current situation among medical staff of county-level hospitals in Southern China. By conducting these studies, we aim to identify factors associated with burnout among medical staff of county-level hospitals in China and provide recommendations for improvement. Methods: Relevant literature on job burnout among medical personnel was searched using the Web of Science Core Collection (WoSCC). CiteSpace was employed for an in-depth cluster analysis to determine research trends and identify the study population. Subsequently, a cross-sectional survey was randomly conducted in three county-level hospitals in Hunan Province of Southern China. Job burnout and satisfaction were assessed using the Maslach Burnout Inventory MBI-Human Services Survey (MBI-HSS) and Job Satisfaction Questionnaire in a total of 362 valid questionnaires collected. The influence factors of the prevalence of job burnout were investigated using logistic regression. Results: In this bibliometric study, 1626 articles were retrieved from 1999 to 2022. China lags behind the United States (US) in both the number and quality of publications in the field of medical staff burnout compared with the US. However, there is a lack of comparative research on job burnout across different job types. County-level medical staff articles are more in line with research hotspots in the field. In total, 362 valid questionnaires were obtained. The total incidence of job burnout among rural medical staff was 27.3 %. Nurses (p

BackgroundSarcopenia is a condition characterized by the age-related loss of skeletal muscle mass and function. The pathogenesis of the disease is influenced by chronic low-grade inflammation. However, the specific changes in the immune landscape changes of sarcopenic muscle are not yet fully understood.MethodsTo gain insights into the immune cell composition and interactions, we combined single-nucleus RNA sequencing data, bulk RNA sequencing dataset, and comprehensive bioinformatic analyses on the skeletal muscle samples from young, aged, and sarcopenic individuals. Histological staining was then performed on skeletal muscles to validate the distribution of immune cells in clinical samples.ResultsWe analyzed the transcriptomes of 101,862 single nuclei, revealing a total of 10 major cell types and 6 subclusters of immune cell types within the human skeletal muscle tissues. Notable variations were identified in the immune microenvironment between young and aged skeletal muscle. Among the immune cells from skeletal muscle microenvironment, macrophages constituted the largest fraction. A specific marker gene LYVE1 for skeletal muscle resident macrophages was further identified. Cellular subclasses included four distinct groups of resident macrophages, which play different roles in physiological or non-physiological conditions. Utilizing bulk RNA sequencing data, we observed a significant enrichment of macrophage-rich inflammation in sarcopenia.ConclusionsOur findings demonstrate age-related changes in the composition and cross-talk of immune cells in human skeletal muscle microenvironment, which contribute to chronic inflammation in aged or sarcopenia muscle. Furthermore, macrophages emerge as a potential therapeutic target, thus advancing our understanding of the pathogenesis of sarcopenia.

Aiming at the problems that the traditional image recognition technology is challenging to extract useful features and the recognition time is extended; the AlexNet model is improved to improve the effect of image classification and recognition. This study focuses on 8 types of tomato leaf diseases and healthy leaves. By using HOG and LBP weighted fusion to extract image features, a tomato leaf disease recognition model based on the AlexNet model is proposed, and transfer learning is used to train the AlexNet model. Transfer the knowledge learned by the AlexNet model on the PlantVillage image dataset to this model while reducing the number of fully connected layers. Keras deep learning framework and programming language Python were used. The model was implemented, and the classification and identification of tomato leaf diseases were carried out. The recognition rate of feature-weighted fusion classification is higher than that of serial and parallel methods, and the recognition time is the shortest. When the weight coefficient ratio of HOG and LBP is 3:7, the image recognition rate is the highest, and its value is 97.2 %. From the model performance curve See, when the number of iterations is more than 150 times, the training set and test accuracy rate both exceed 97 %, the loss rate shows a gradient decline, and the change is relatively stable; compared with the traditional AlexNet model, HOG + LBP + SVM model, and VGG model, improved AlexNet model has the highest recognition rate, and it has high recall value, accuracy, and F1 value; Compared with the latest convolutional neural network disease recognition models, improved AlexNet model recognition accuracy was 98.83 %, and the F1 value was 0.994. It shows that the model has good convergence performance, fast prediction speed, and low loss rate and can effectively identify 8 types of tomato leaf images, which provides a reference for the research on crop disease identification.

BackgroundDisorders of consciousness (DoC) represent a spectrum of neurological conditions that pose significant treatment challenges. Percutaneous short-term spinal cord stimulation (SCS) has emerged as a promising experimental diagnostic treatment to assess and potentially improve consciousness levels. However, the effectiveness of this intervention is frequently compromised by the shift of electrodes, particularly in the cervical region, which can negatively affect therapeutic outcomes.MethodsThis retrospective study aimed to study if electrodes shift in percutaneous short-term SCS in patients with DoC would affect the outcome. We analyzed the relationship between electrode shift length and patient outcome, as well as the correlation with various anatomical parameters, including the actual length of the cervical spine, linear length, spinal canal transverse diameter, spinal canal diameter, and C2 cone height, in a cohort of patients undergoing the procedure.ResultsOur findings revealed that in patients with better outcome, there are significant less patient with electrode shift (p = 0.019). Further, a linear correlation was found between the length of electrode shift and patients’ outcome (Rho = 0.583, p = 0.002), with longer shift lengths associated with poorer outcomes. Contrary to our expectations, there was no significant association between the measured anatomical parameters and the extent of electrode shift. However, a trend was found between the actual length of the cervical spine and the shift of the electrode (p = 0.098). Notably, the shorter spinal canal transverse diameter was found to be significantly associated with better outcome in patients with DoC receiving percutaneous short-term SCS (p = 0.033).ConclusionThese results highlight the clinical importance of electrode stability in the cervical region during SCS treatment for patients with DoC. Ensuring secure placement of electrodes may play a crucial role in enhancing patients’ outcome and minimize postoperative complications. Given the lack of association with expected anatomical parameters, future research should investigate other factors that could impact electrode stability to optimize this therapeutic intervention.

ObjectiveTo explore the mediating roles of activities of daily living (ADL) and economic burden of diseases in the relationship between chronic diseases and depressive symptoms of older adults.MethodsThe data were sourced from China Health and Retirement Longitudinal Study (CHARLS). The number of chronic diseases, ADL, out-of-pocket medical expenses and the Center for Epidemiological Studies Depression Scale (CES-D) were selected as measuring indexes. Mediation analysis was conducted to explore the potential mediating roles of ADL and economic burden of diseases in the association between chronic diseases and depressive symptoms.ResultsThe number of chronic diseases, ADL, economic burden of diseases and depressive symptoms of older adults were significantly correlated with each other. ADL and economic burden of diseases individually mediated the relationship between the number of chronic diseases and depressive symptoms, accounting for 31.460% and 5.471% of the total effect, respectively. Additionally, ADL and economic burden of diseases demonstrated a chain mediating effect in this relationship, contributing to 0.759% of the total effect.ConclusionThe chain-mediated model effectively elucidated the mediating roles of ADL and economic burden of diseases in the association between chronic diseases and depressive symptoms among older adults. The study underscores the need for policymakers to focus attentively on the mental health of older adults with chronic diseases. Enhancing the capacity for ADL and strengthening social security to mitigate the economic burden of diseases are recommended strategies to alleviate depressive symptoms in older adults.

Luteolin, a monomeric substance, is a natural product of the Brucea javanica (BJ) plant. Brucea javanica oil emulsion injection (BJOEI) is a proprietary Chinese medicine purified from BJ that is widely used clinically as an anti-tumor treatment. Although a growing body of research suggests that luteolin and BJOEI have anti-tumor effects, the molecular mechanism of action has not been fully elucidated. In this study, through molecular docking technology, we found that luteolin can interact directly with GPSM2 and regulate the FoxO signaling pathway through GPSM2. In addition, the inhibitory effect of luteolin on colon adenocarcinoma (COAD) cells was found to be offset by knockdown of GPSM2. In contrast, the anti-proliferative effects of luteolin could be notably reversed by overexpression of GPSM2. The results reveal that GPSM2 is crucial in luteolin-mediated anti-proliferative effects. The mediation of anti-proliferative effects by GPSM2 has also been indirectly demonstrated in RKO and SW480 xenograft mice models. In addition, we verified that BJOEI inhibits the progression of COAD by mediating GPSM2 and regulating the FoxO signaling pathway. We also found that BJOEI achieved a better anti-tumor effect when combined with fluorouracil injection. Collectively, our data show that the anti-tumor effects of BJOEI and luteolin on COAD are GPSM2-dependent and downregulating the expression of GPSM2 to regulate the FoxO signaling pathway may be an effective way to treat COAD.

Background: Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment. Methods: We retrospectively analysed patients with stage IIIA–IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST. Findings: The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS. Interpretation: RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.

ABSTRACT: Relationships between texture measurements and meat water properties were investigated in raw intact broiler breast fillets with the wooden breast (WB) condition. Texture measurements included subjective WB scores and blunt Meullenet-Owens Razor Shear (BMORS). Water properties were determined with low-field nuclear magnetic resonance (LF-NMR). Spearman correlation was used to estimate relationships between WB scores and water properties, while Pearson correlation was used for relationships between BMORS force and water properties. LF-NMR measurements exhibited 3 water components: protein-associated or hydration water T2b, intra-myofibrillar water or immobilized water T21, and extra-myofibrillar water or free water T22 in chicken breast meat. Significant and strong Spearman correlations were found between the WB scores and T21 time constant, the abundance (normalized areas) of T22, and the proportion of T21 and T22 (rs > 0.60, P < 0.001). Strong Pearson correlations (r = 0.72) were noted only between the T21 time constant and BMORS force. These results demonstrate that water may contribute to the specific texture characteristics measured with subjective WB scoring (palpable hardness and rigidity) and BMORS (hardness and share force) in raw broiler breast fillets with the WB condition.

Coal is the main energy source in China, and the western region in China is the main coal production area. The protection and utilization of coal mine water is the major technical challenge in the coal mining. The coal green mining research team of China Energy Group has pioneered the technology of underground coal mine reservoirs, which has been widely implemented in the Shendong mining area in Western China, providing over 95% of water needed for mining and ensuring the sustainable development of the mining area. To further enrich and improve the theoretical and technical system of underground coal mine reservoirs, this technology has been promoted and applied under different geological and working conditions in the western coal mining areas to ensure national energy security and water resources protection. The research team has built the original technology experimental platform system for coal mine underground reservoirs, including the comprehensive intelligent experimental platform for underground water transport and protection, the physical modelling platform for coal mine underground reservoirs under multiple coal seams, the dam structure experimental platform for coal mine underground reservoirs, the simulation experimental platform for deep well construction in western areas, the water-rock coupling mechanism experimental platform for underground water reservoirs, the integrated water treatment process experimental platform, and the impact experimental platforms for coal mine underground reservoirs, etc. On these platforms, the researches can be carried out consisting of the transport law of underground water, the optimization of dam structure parameters, the safety and stability of reservoirs, water-rock coupling mechanism, the optimization of mine water treatment, and the impact of caving rock mass on the dam structure under different coal seam occurrence conditions in the western mining areas of China. These platform systems provide a theoretical support and technical verification for the construction, operation, and safety of coal mine underground reservoirs. By utilizing these experimental platforms, various experimental research studies have been conducted, including the stability and seepage of coal mine underground reservoirs under multiple coal seams, the structural safety of coal mine underground reservoirs dam, and the water-rock coupling mechanism of coal mine underground reservoirs. These research results have been applied in actual engineering practice to ensure the safe and stable operation of coal mine underground reservoirs.

Abstract Background Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. Results In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. Conclusions Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.

Residual stress is caused by non–uniform deformation caused by non–uniform force, heat and composition, which is of great significance in engineering applications. It is assumed that the residual stress is always the upper limit of the elastic limit, so the reduction of the flow stress will reduce the residual elastic stress. It is particularly important to control the flow stress in metal materials. Compared with traditional methods, the use of electropulsing treatment (EPT) technology stands out due to its energy–efficient, highly effective, straightforward and pollution–free characteristics. However, there are different opinions about the mechanism of reducing flow stress through EPT due to the conflation of the effects from pulsed currents. Herein, a clear correlation is identified between induced stress levels and the application of pulsed electrical current. It was found that the decrease in flow stress is positively correlated with the current density and the duration of electrical contact and current action time. We first systematically and comprehensively summarize the influence mechanisms of EPT on dislocations, phase, textures and recrystallization. An analysis of Joule heating, electron wind effect, and thermal–induced stress within metal frameworks under the influence of pulsed currents was conducted. And the distribution of electric, thermal and stress fields under EPT are discussed in detail based on a finite element simulation (FES). Finally, some new insights into the issues and challenges of flow stress drops caused by EPT are proposed, which is critically important for advancing related mechanism research and the revision of theories and models.

Abstract Background Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). Methods LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH−). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. Results LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. Conclusions Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.

Abstract Deep learning has achieved a notable success in mass spectrometry-based proteomics and is now emerging in glycoproteomics. While various deep learning models can predict fragment mass spectra of peptides with good accuracy, they cannot cope with the non-linear glycan structure in an intact glycopeptide. Herein, we present DeepGlyco, a deep learning-based approach for the prediction of fragment spectra of intact glycopeptides. Our model adopts tree-structured long-short term memory networks to process the glycan moiety and a graph neural network architecture to incorporate potential fragmentation pathways of a specific glycan structure. This feature is beneficial to model explainability and differentiation ability of glycan structural isomers. We further demonstrate that predicted spectral libraries can be used for data-independent acquisition glycoproteomics as a supplement for library completeness. We expect that this work will provide a valuable deep learning resource for glycoproteomics.

Abstract Identifying key patterns of tactics implemented by rival teams, and developing effective responses, lies at the heart of modern football. However, doing so algorithmically remains an open research challenge. To address this unmet need, we propose TacticAI, an AI football tactics assistant developed and evaluated in close collaboration with domain experts from Liverpool FC. We focus on analysing corner kicks, as they offer coaches the most direct opportunities for interventions and improvements. TacticAI incorporates both a predictive and a generative component, allowing the coaches to effectively sample and explore alternative player setups for each corner kick routine and to select those with the highest predicted likelihood of success. We validate TacticAI on a number of relevant benchmark tasks: predicting receivers and shot attempts and recommending player position adjustments. The utility of TacticAI is validated by a qualitative study conducted with football domain experts at Liverpool FC. We show that TacticAI’s model suggestions are not only indistinguishable from real tactics, but also favoured over existing tactics 90% of the time, and that TacticAI offers an effective corner kick retrieval system. TacticAI achieves these results despite the limited availability of gold-standard data, achieving data efficiency through geometric deep learning.

Abstract Background Microbiota are closely associated with human health and disease. Metaproteomics can provide a direct means to identify microbial proteins in microbiota for compositional and functional characterization. However, in-depth and accurate metaproteomics is still limited due to the extreme complexity and high diversity of microbiota samples. It is generally recommended to use metagenomic data from the same samples to construct the protein sequence database for metaproteomic data analysis. Although different metagenomics-based database construction strategies have been developed, an optimization of gene taxonomic annotation has not been reported, which, however, is extremely important for accurate metaproteomic analysis. Results Herein, we proposed an accurate taxonomic annotation pipeline for genes from metagenomic data, namely contigs directed gene annotation (ConDiGA), and used the method to build a protein sequence database for metaproteomic analysis. We compared our pipeline (ConDiGA or MD3) with two other popular annotation pipelines (MD1 and MD2). In MD1, genes were directly annotated against the whole bacterial genome database; in MD2, contigs were annotated against the whole bacterial genome database and the taxonomic information of contigs was assigned to the genes; in MD3, the most confident species from the contigs annotation results were taken as reference to annotate genes. Annotation tools, including BLAST, Kaiju, and Kraken2, were compared. Based on a synthetic microbial community of 12 species, it was found that Kaiju with the MD3 pipeline outperformed the others in the construction of protein sequence database from metagenomic data. Similar performance was also observed with a fecal sample, as well as in silico mixed datasets of the simulated microbial community and the fecal sample. Conclusions Overall, we developed an optimized pipeline for gene taxonomic annotation to construct protein sequence databases. Our study can tackle the current taxonomic annotation reliability problem in metagenomics-derived protein sequence database and can promote the in-depth metaproteomic analysis of microbiome. The unique metagenomic and metaproteomic datasets of the 12 bacterial species are publicly available as a standard benchmarking sample for evaluating various analysis pipelines. The code of ConDiGA is open access at GitHub for the analysis of microbiota samples. Video Abstract

Abstract Background & Aims Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study. Methods Two-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings. Results ABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824–59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013–1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884–0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020–0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743–34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217–51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value

[Objective] The structural reliability of the transmission shaft of guideway rubber-tyred train is crucial to the safety of train operation. During the ice and snow test on a certain urban rail transit line, the guideway rubber-tyred train failed several times resulting from the fracture of the transmission shaft. Therefore, it is necessary to analyze the fracture causes of the transmission shaft and optimize its design. [Method] The causes of the fracture of the transmission shaft are analyzed from two aspects: macroscopic detection of the failure shaft section, physical and chemical detection of the failure material. A wireless torque test system is used to test the real-time load of the transmission shaft between stations 5-6 and stations 5-7 on the line. The test results are analyzed, and the structure of the transmission shaft is optimized. The strength test on the optimized transmission shaft bench and the fatigue test on the optimized transmission shaft are carried out respectively. [Result & Conclusion] The causes of transmission shaft fracture are identified as the overload brittle fracture of cross shaft and fatigue fracture of double coupling bushing. The test results from the above two line sections show that all the maximum torques of the shaft occur when the vehicle is slipping. Though the actual torque of transmission shaft is less than the designed maximum working torque, the impact energy on the shaft is much larger than the torque change value under normal working conditions because the torque changes within a very short time. The measures that are taken to optimize the transmission shaft structure are as follows: increasing the shaft diameter of the cross shaft, increasing the chamfer angle of the cross shaft arc transition, and further reducing the stress concentration. The strength of the shaft shoulder of the double coupling bushing is increased by adding the reinforcing rib on it. The strength test on the optimized transmission shaft bench shows that it meets the design requirements and passes its fatigue test.

Abstract Background The impact of antidepressants on Inflammatory bowel diseases (IBD) has been extensively studied. However, the biological effects and molecular mechanisms of antidepressants in alleviating colitis remain unclear. Methods We systematically assessed how antidepressants (fluoxetine, fluvoxamine and venlafaxine) affected IBD and chose fluoxetine, the most effective one, for mechanism studies. We treated the C56BL/6 mice of the IBD model with fluoxetine and their controls. We initially assessed the severity of intestinal inflammation in mice by body weight loss, disease Activity Index scores and the length of the colon. The H&E staining and immunohistochemical staining of MUC2 of colon sections were performed to observe the pathological changes. RT-qPCR and western blot were conducted to assess the expression level of the barrier and inflammation-associated genes. Then, single-cell RNA sequencing was performed on mouse intestinal mucosa. Seurat was used to visualize the data. Uniform Manifold Approximation and Projection (UMAP) was used to perform the dimensionality reduction. Cell Chat package was used to perform cell–cell communication analysis. Monocle was used to conduct developmental pseudotime analysis. Last, RT-qPCR, western blot and immunofluorescence staining were conducted to test the phenomenon discovered by single-cell RNA sequencing in vitro. Results We found that fluoxetine treatment significantly alleviated colon inflammation. Notably, single-cell RNA sequencing analysis revealed that fluoxetine affected the distribution of different cell clusters, cell–cell communication and KEGG pathway enrichment. Under the treatment of fluoxetine, enterocytes, Goblet cells and stem cells became the dominating cells. The pseudotime analysis showed that there was a trend for M1 macrophages to differentiate into M2 macrophages. Lastly, we tested this phenomenon in vitro, which exhibited anti-inflammatory effects on enterocytes. Conclusions Fluoxetine exhibited anti-inflammatory effects on intestinal mucosa via remodeling of the intestinal cells and macrophages, which reveals that fluoxetine is a promising therapeutic drug for the treatment of IBD and psychiatric comorbidities.

Abstract Previous studies have proved circFN1 is highly expressed in acute myeloid leukemia (AML) patients and AML cell lines. This study aims to investigate the impact of circFN1 on AML and its mechanism. Via real‐time quantitative PCR to detect circFN1, miR‐1294, ARHGEF10L expressions in clinical plasma samples and AML cell lines, AML cells were cultured in vitro and transfected with si‐circFN1, pcDNA3.1‐circFN1, and si‐ARHGEF10L, respectively, or co‐transfected pcDNA3.1‐circFN1 + miR‐1294 mimic and pcDNA3.1‐circFN1 + si‐ARHGEF10L. Using dual luciferase reporter experiment to detect the relationship between circFN1 and miR‐1294, as well as miR‐1294 and ARHGEF10L. CCK‐8 was used to detect cell proliferation, Transwell to cell invasion, TUNEL staining and flow cytometry to detect cell apoptosis, RT‐qPCR to circFN1 RNA, miR‐1294, and ARHGEF10L expression levels in HL‐60 cells, and western blot to ARHGEF10L protein expression level in HL‐60 cells. We found highly expressed circFN1 and ARHGEF10L, as well as low‐expressed miR‐1294 in AML patients and AML cell lines. In contrast to si‐NC group, si‐circFN1 group could signally inhibit HL‐60 cell proliferation and migration, but promote cell apoptosis; compared with mimic NC group, miR‐1294 mimic group could visually inhibit HL‐60 cell proliferation and migration, but promote cell apoptosis. miR‐1294 was the target of circFN1, and ARHGEF10L was the target of miR‐1294. Over‐expressing miR‐1294 or silencing ARHGEF10L could signally inhibit circFN1 promoting HL‐60 cell proliferation and migration and repressing cell apoptosis. circFN1 promotes proliferation and invasion of AML cell and represses cell apoptosis via regulating miR‐1294/ARHGEF10L axis, which provides new insight for molecular targeted‐treatment for AML.