Construction of prognostic markers for gastric cancer and comprehensive analysis of pyroptosis-related long non-coding RNAs.

BACKGROUND: China's most frequent malignancy is gastric cancer (GC), which has a very poor survival rate, and the survival rate for patients with advanced GC is dismal. Pyroptosis has been connected to the genesis and development of cancer. The function of pyroptosis-related long non-coding RNAs (PRLs) in GC, on the other hand, remains uncertain. AIM: To explore the construction and comprehensive analysis of the prognostic characteristics of long non-coding RNA (lncRNA) related to pyroptosis in GC patients. METHODS: The TCGA database provided us with 352 stomach adenocarcinoma samples, and we obtained 28 pyroptotic genes from the Reactome database. We examined the correlation between lncRNAs and pyroptosis using the Pearson correlation coefficient. Prognosis-related PRLs were identified through univariate Cox analysis. A predictive signature was constructed using stepwise Cox regression analysis, and its reliability and independence were assessed. To facilitate clinical application, a nomogram was created based on this signature. we analyzed differences in immune cell infiltration, immune function, and checkpoints between the high-risk group (HRG) and low-risk group (LRG). RESULTS: Five hundred and twenty-three PRLs were screened from all lncRNAs (absolute correlation coefficient > 0.4, P < 0.05). Nine PRLs were included in the risk prediction signature that was created through stepwise Cox regression analysis. We determined the risk score for GC patients and employed the median value as the dividing line between HRG and LRG. The ability of the risk signature to predict the overall survival (OS) of GC is demonstrated by the Kaplan-Meier analysis, risk curve, receiver operating characteristic curve, and decision curve analysis curve. The risk signature was shown to be an independent prognostic factor for OS in both univariate and multivariate Cox regression analyses. HRG showed a more efficient local immune response or modulation compared to LRG, as indicated by the predicted signal pathway analysis and examination of immune cell infiltration, function, and checkpoints (P < 0.05). CONCLUSION: In general, we have created a brand-new prognostic signature using PRLs, which may provide ideas for immunotherapy in patients with GC.

The Ability of Different Tea Tree Germplasm Resources in South China to Aggregate Rhizosphere Soil Characteristic Fungi Affects Tea Quality.

It is generally recognized that the quality differences in plant germplasm resources are genetically determined, and that only a good "pedigree" can have good quality. Ecological memory of plants and rhizosphere soil fungi provides a new perspective to understand this phenomenon. Here, we selected 45 tea tree germplasm resources and analyzed the rhizosphere soil fungi, nutrient content and tea quality. We found that the ecological memory of tea trees for soil fungi led to the recruitment and aggregation of dominant fungal populations that were similar across tea tree varieties, differing only in the number of fungi. We performed continuous simulation and validation to identify four characteristic fungal genera that determined the quality differences. Further analysis showed that the greater the recruitment and aggregation of Saitozyma and Archaeorhizomyces by tea trees, the greater the rejection of Chaetomium and Trechispora, the higher the available nutrient content in the soil and the better the tea quality. In summary, our study presents a new perspective, showing that ecological memory between tea trees and rhizosphere soil fungi leads to differences in plants' ability to recruit and aggregate characteristic fungi, which is one of the most important determinants of tea quality. The artificial inoculation of rhizosphere fungi may reconstruct the ecological memory of tea trees and substantially improve their quality.

Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity.

Nucleophosmin 1 (NPM1) is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Concurrent inflammatory bowel diseases (IBD) and MDS are common, indicating a close relationship between IBD and MDS. Here we examined the function of NPM1 in IBD and colitis-associated colorectal cancer (CAC). NPM1 expression was reduced in patients with IBD. Npm1+/- mice were more susceptible to acute colitis and experimentally induced CAC than littermate controls. Npm1 deficiency impaired the function of interleukin-22 (IL-22)-producing group three innate lymphoid cells (ILC3s). Mice lacking Npm1 in ILC3s exhibited decreased IL-22 production and accelerated development of colitis. NPM1 was important for mitochondrial biogenesis and metabolism by oxidative phosphorylation in ILC3s. Further experiments revealed that NPM1 cooperates with p65 to promote mitochondrial transcription factor A (TFAM) transcription in ILC3s. Overexpression of Npm1 in mice enhanced ILC3 function and reduced the severity of dextran sulfate sodium-induced colitis. Thus, our findings indicate that NPM1 in ILC3s protects against IBD by regulating mitochondrial metabolism through a p65-TFAM axis.

Changes in the growth and physiological property of tea tree after aviation mutagenesis and screening and functional verification of its characteristic hormones.

Aerospace breeding is a breeding technique that utilizes a spacecraft to position plants in a space environment for mutagenesis, which is conducive to rapid mutagenesis for the screening of superior plant varieties. In this study, tea trees with aviation mutagenesis (TM) and those without aviation mutagenesis (CK) were selected as research subjects to analyze the effects of aviation mutagenesis on the growth, physiological properties, and hormone metabolism of tea trees, and to further screen the characteristic hormones and validate their functions. The results showed that the leaf length, leaf width, and leaf area of TM tea trees were significantly larger than those of CK. The growth indexes, the photosynthetic physiological indexes (i.e., chlorophyll content, intercellular CO2 concentration, stomatal conductance, transpiration rate, and photosynthetic rate), and the resistance physiological indexes (i.e., superoxide dismutase, peroxidase, catalase, and soluble sugar) were significantly higher in TM than in CK. Hormone metabolome analysis showed that four characteristic hormones distinguished CK from TM, namely, l-tryptophan, indole, salicylic acid, and salicylic acid 2-O-ß-glucoside, all of which were significantly more abundant in TM than in CK. These four characteristic hormones were significantly and positively correlated with the growth indexes, tea yield, and the photosynthetic and resistance physiological indexes of tea trees. The leaf area, chlorophyll content, photosynthetic rate, and superoxide dismutase activity of tea tree seedlings after spraying with the four characteristic hormones were significantly increased, in which salicylic acid and salicylic acid 2-O-ß-glucoside were more favorable to increase the leaf area and superoxide dismutase activity, while l-tryptophan and indole were more favorable to increase the leaf chlorophyll content and photosynthetic rate. It can be observed that aviation mutagenesis improves the accumulation of the characteristic hormones of tea trees, enhances their photosynthetic capacity, improves their resistance, promotes their growth, and then improves the tea yield.

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure.

BACKGROUND: When massive necrosis occurs in acute liver failure (ALF), rapid expansion of HSCs called liver progenitor cells (LPCs) in a process called ductular reaction is required for survival. The underlying mechanisms governing this process are not entirely known to date. In ALF, high levels of retinoic acid (RA), a molecule known for its pleiotropic roles in embryonic development, are secreted by activated HSCs. We hypothesized that RA plays a key role in ductular reaction during ALF. METHODS: RNAseq was performed to identify molecular signaling pathways affected by all-trans retinoid acid (atRA) treatment in HepaRG LPCs. Functional assays were performed in HepaRG cells treated with atRA or cocultured with LX-2 cells and in the liver tissue of patients suffering from ALF. RESULTS: Under ALF conditions, activated HSCs secreted RA, inducing RARα nuclear translocation in LPCs. RNAseq data and investigations in HepaRG cells revealed that atRA treatment activated the WNT-ß-Catenin pathway, enhanced stemness genes (SOX9, AFP, and others), increased energy storage, and elevated the expression of ATP-binding cassette transporters in a RARα nuclear translocation-dependent manner. Further, atRA treatment-induced pathways were confirmed in a coculture system of HepaRG with LX-2 cells. Patients suffering from ALF who displayed RARα nuclear translocation in the LPCs had significantly better MELD scores than those without. CONCLUSIONS: During ALF, RA secreted by activated HSCs promotes LPC activation, a prerequisite for subsequent LPC-mediated liver regeneration.

Structurally diverse diterpenoids from the leaves of Croton mangelong and their anti-diabetic activity.

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.

The HPE1 RNA-binding protein modulates chloroplast RNA editing to promote photosynthesis under cold stress in Arabidopsis.

Cold stress has severe negative consequences for plant growth and crop yield. Here, we report that an Arabidopsis thaliana mutant that lacks the HPE1 gene, which encodes an RNA-binding protein, maintains higher photosynthetic activity under cold stress, together with higher accumulation of thylakoid proteins. We showed that HPE1 interacts with MORF2 and MORF9 and thereby mediates RNA editing in chloroplasts. Loss of HPE1 function increased the editing efficiency at four RNA editing sites, rpoC-488, ndhB-149, ndhB-746 and matK-706, under cold stress and altered the expression of nuclear photosynthesis-related genes and cold-responsive genes. We propose that HPE1-mediated RNA editing acts as a trigger for retrograde signaling that affects photosynthesis under cold stress.

Effects of levetiracetam on bone mineral density and bone metabolism in patients with epilepsy: A systematic review and meta-analysis.

PURPOSE: The effects of levetiracetam (LEV) on bone mineral density (BMD) and bone metabolism are currently inconclusive, and this study was designed to answer this question. METHODS: Citations from PubMed, Embase, Cochrane Library, and Web of Science databases (up to February 4, 2024) were reviewed. The effects of LEV on BMD as well as bone metabolism indicators were measured by calculating the standardized mean difference (SMD) with a 95% confidence interval (CI). This study was registered with PROSPERO (CRD42024509560). RESULTS: A total of 612 individuals from 13 studies were included in the present analysis. Of the items related to bone metabolism, LEV was found to be associated significantly with decreased serum calcium with an SMD of -0.47 (95 % CI, -0.77- -0.16; p = 0.04). However, changes in other markers (including serum phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and parathyroid hormone) were not statistically significantly correlated with the use of LEV (p > 0.05). Also, when compared to the control groups, the changes in BMD of the observation groups were not significant (p > 0.05). CONCLUSIONS: The use of LEV may significantly reduce serum calcium in patients with epilepsy, and regular monitoring of bone metabolism-related indicators is recommended.

Astrocyte-specific activation of sigma-1 receptors in mPFC mediates the faster onset antidepressant effect by inhibiting NF-κB-induced neuroinflammation.

Major depressive disorder (MDD) is a global health burden characterized by persistent low mood, deprivation of pleasure, recurrent thoughts of death, and physical and cognitive deficits. The current understanding of the pathophysiology of MDD is lacking, resulting in few rapid and effective antidepressant therapies. Recent studies have pointed to the sigma-1 (σ-1) receptor as a potential rapid antidepressant target; σ-1 agonists have shown promise in a variety of preclinical depression models. Hypidone hydrochloride (YL-0919), an independently developed antidepressant by our institute with faster onset of action and low rate of side effects, has recently emerged as a highly selective σ-1 receptor agonist; however, its underlying astrocyte-specific mechanism is unknown. In this study, we investigated the effect of YL-0919 treatment on gene expression in the prefrontal cortex of depressive-like mice by single-cell RNA sequencing. Furthermore, we knocked down σ-1 receptors on astrocytes in the medial prefrontal cortex of mice to explore the effects of YL-0919 on depressive-like behavior and neuroinflammation in mice. Our results demonstrated that astrocyte-specific knockdown of σ-1 receptor resulted in depressive-like behavior in mice, which was reversed by YL-0919 administration. In addition, astrocytic σ-1 receptor deficiency led to activation of the NF-κB inflammatory pathway, and crosstalk between reactive astrocytes and activated microglia amplified neuroinflammation, exacerbating stress-induced neuronal apoptosis. Furthermore, the depressive-like behavior induced by astrocyte-specific knockdown of the σ-1 receptor was improved by a selective NF-κB inhibitor, JSH-23, in mice. Our study not only reaffirms the σ-1 receptor as a key target of the faster antidepressant effect of YL-0919, but also contributes to the development of astrocytic σ-1 receptor-based novel drugs.

Risk factor evaluation of cuff pressure of >30 cmH2O to stop air leakage during mechanical ventilation: A prospective observational study.

AIM: The commonly recommended endotracheal tube cuff pressure is 20-30 cmH2O. However, some patients require a cuff pressure of >30 cmH2O to prevent air leakage. The study aims to determine the risk factors that contribute to the endotracheal tube cuff pressure of >30 cmH2O to prevent air leakage. DESIGN: A multi-centre prospective observational study. METHODS: Eligible patients undergoing mechanical ventilation in the intensive care unit of three hospitals between March 2020 and July 2022 were included. The endotracheal tube cuff pressure to prevent air leakage was determined using the minimal occlusive volume technique. The patient demographics and clinical information were collected. RESULTS: A total of 284 patients were included. Among these patients, 55 (19.37%) patients required a cuff pressure of >30 cmH2O to prevent air leakage. The multivariate logistic regression results revealed that the surgical operation (odds ratio [OR]: 8.485, 95% confidence interval [CI]: 1.066-67.525, p = 0.043) was inversely associated with the endotracheal tube cuff pressure of >30 cmH2O, while the oral intubation route (OR: 0.127, 95% CI: 0.022-0.750, p = 0.023) and cuff inner diameter minus tracheal area (OR: 0.949, 95% CI: 0.933-0.966, p < 0.001) were negatively associated with the endotracheal tube cuff pressure of >30 cmH2O. Therefore, a significant number of patients require an endotracheal tube cuff pressure of ＞30 cmH2O to prevent air leakage. Several factors, including the surgical operation, intubation route, and difference between the cuff inner diameter and tracheal area at the T3 vertebra, should be considered when determining the appropriate cuff pressure during mechanical ventilation.

Cell-free DNA methylation patterns in aging and their association with inflamm-aging.

Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.

Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called 'cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age ­ essentially, how old their body seems based on various health factors, which can differ from their actual age.We also found that these DNA changes could indicate how aging might make the body's defense system ­ which fights off diseases ­ react more intensely. Understanding this could be crucial for managing health as we get older.Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.

Fatigue crack-based strain sensors achieving flow detection and motion monitoring for reconnaissance robot applications.

Crack-based flexible strain sensors with ultra-high sensitivity under tiny strain are highly desired for environmental perception and motion detection of novel flexible and miniature robots. However, previously reported methods for fabricating crack patterns have often sacrificed the cyclic stability of the sensor, leading to a trade-off relationship between the sensitivity and the cyclic stability. Here, a universal and simple strategy based on fatigue loading with an ultra-large cumulative strain of up to ∼1.2 × 107%, rather than the traditionally quasi-static pre-overloading methods, is proposed to introduce channel cracks in the sensing layer without sacrificing the cyclic stability. The developed flexible strain sensors exhibit high strain-sensitivity (gauge factor = 5798) under tiny strain (< 3%), high cyclic stability (15 000 cycles) and a low strain detecting limit (0.02%). Furthermore, a leaf-like mechanosensor is developed using the fatigue crack-based strain sensor for the realization of multifunctional applications in environment perception and micro-motion detection. Brilliant airflow sensing performance with a wide sensing range (0.93-11.93 m s-1) and a fast response time (0.28 s) for amphibious applications is demonstrated. This work provides a new strategy for overcoming limits of crack-based flexible strain sensors and the developed leaf-like mechanosensor shows great application potential in miniature and flexible reconnaissance robots.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Recruitment and Aggregation Capacity of Tea Trees to Rhizosphere Soil Characteristic Bacteria Affects the Quality of Tea Leaves.

There are obvious differences in quality between different varieties of the same plant, and it is not clear whether they can be effectively distinguished from each other from a bacterial point of view. In this study, 44 tea tree varieties (Camellia sinensis) were used to analyze the rhizosphere soil bacterial community using high-throughput sequencing technology, and five types of machine deep learning were used for modeling to obtain characteristic microorganisms that can effectively differentiate different varieties, and validation was performed. The relationship between characteristic microorganisms, soil nutrient transformation, and tea quality formation was further analyzed. It was found that 44 tea tree varieties were classified into two groups (group A and group B) and the characteristic bacteria that distinguished them came from 23 genera. Secondly, the content of rhizosphere soil available nutrients (available nitrogen, available phosphorus, and available potassium) and tea quality indexes (tea polyphenols, theanine, and caffeine) was significantly higher in group A than in group B. The classification result based on both was consistent with the above bacteria. This study provides a new insight and research methodology into the main reasons for the formation of quality differences among different varieties of the same plant.

Effect of varying cuff sizes with identical inner diameter on endotracheal intubation in critically ill adults: A sealed tracheal controlled trial.

BACKGROUND: The present study aims to determine the impact of different cuff diameters on the cuff pressure of endotracheal tubes (ETTs) when the trachea is adequately sealed. METHODS: In the present single-center clinical trial, adult patients who underwent cardiothoracic surgery were assigned to use ETTs from 2 brands (GME and GZW). The primary endpoint comprised of the following: cuff diameter, inner diameter of the ETT, manufacturer, and the number of subjects with tracheal leakage when the cuff pressure was 30 cm H2O. RESULTS: A total of 298 patients were assigned into 2 groups, based on the 2 distinct brands of ETTs: experimental group (n = 122, GME brand) and control group (n = 176, GZW brand). There were no significant differences in baseline characteristics. However, the cuff diameter was significantly smaller in the control group, when compared to the experimental group (P = .001), and the incidence of tracheal leakage was significantly higher in the control group (P = .001). Furthermore, the GME brand ETT had a significantly larger cuff diameter, when compared to the GZW brand ETT. CONCLUSION: The cuff size would mismatch the tracheal area in clinical practice. Therefore, chest computed tomography is recommended to routinely evaluate the tracheal cross-sectional area during anesthesia, in order to ensure the appropriate cuff size selection.

GPR160 regulates the self-renewal and pluripotency of mouse embryonic stem cells via JAK1/STAT3 signal pathway.

G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and regulate various physiological and pathological processes. Despite extensive studies, the roles of GPCRs in mouse embryonic stem cells (mESCs) remain poorly understood. Here, we show that GPR160, a class A member of GPCRs, is dramatically downregulated concurrent with mESC differentiation into embryoid bodies in vitro. Knockdown of Gpr160 leads to downregulation of the expression of pluripotency-associated transcription factors and upregulation of the expression of lineage markers, accompanying with the arrest of the mESC cell-cycle in the G0/G1 phase. RNA-seq analysis shows that GPR160 participates in the JAK/STAT signaling pathway crucial for maintaining ESC stemness, and the knockdown of GPRGpr160 results in the downregulation of STAT3 phosphorylation level, which in turn is partially rescued by colivelin, a STAT3 activator. Consistent with these observations, GPR160 physically interacts with JAK1, and cooperates with leukemia inhibitory factor receptor (LIFR) and gp130 to activate the STAT3 pathway. In summary, our results suggest that GPR160 regulates mESC self-renewal and pluripotency by interacting with the JAK1-LIFR-gp130 complex to mediate the JAK1/STAT3 signaling pathway.

Prediction of the Effects of Pulsating Hydraulic Fracturing on the Porous Structure and Permeability of Coal Based on NMR and AE Spectra.

Pulsating hydraulic fracturing has been an environmentally friendly method to improve the permeability of rock formations to stimulate gas production and reduce hazard risks. It has the advantage of fracturing the reservoir with lower cracking pressure and less water volume, as the mechanical strength of rock materials has been reduced by the hydraulic pulse pressure. Many researchers have found significant changes in hard rocks after cyclic loading. However, the existing work still cannot clearly explain the mechanism of the rock damage by pulsating hydraulic fracturing within a short-time experiment. To solve the issue, an investigation of the effects of pulsating hydraulic fracturing on CBM production has been carried out in lab and field applications. Results indicate that the long-term hydraulic pulse pressure can cause a linear decline in cracking pressure directly measured in the lab. It plays an essential role in the permeability enhancement by generating more flow channels for CBM production. The low-field NMR quantitatively evaluates the increase in porosity, which reveals significant incremental ratios of over 20% in the porosity of macropores, mesopores, and micropores of coal caused by fatigue damage. It is first proven that hydraulic pulse pressure has a significant influence on the porosity components of macropores, mesopores, and micropores. To validate the effectiveness of the technique on the field scale, a field application of pulsating hydraulic fracturing has been carried out in a coal mine. It shows that gas production has been largely enhanced with a long and stable production stage and higher gas flux after the applied pulsating load. The gas concentration and gas flux of the fractured boreholes are about 2 times that of the nonfractured boreholes. This work provides an investigation of the effects of pulsating hydraulic fracturing on CBM production, which gives a better understanding of the mechanism for the engineers in the field.

Serum IgA as a Prognostic Beacon: Anticipating Systemic Therapy Efficacy in Metastatic Clear Cell Renal Cell Carcinoma.

OBJECTIVE: Immunotherapy-tyrosine kinase inhibitor (IO-TKI) therapy has revolutionized the treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC); however, the absence of effective biomarkers poses a challenge in predicting the efficacy of these regimens. This study aims to explore the predictive and prognostic value of serum immunoglobulin A (IgA) in mccRCC patients undergoing IO-TKI therapy. METHODS: Ninety-six mccRCC patients treated with IO-TKI therapy from 2019 to 2023 were enrolled and serum IgA levels were assessed at the pretreatment baseline and after 3 months of treatment. RESULTS: Notably, baseline levels of IgA showed no correlation with the objective response rate. However, patients achieving complete or partial responses exhibited a remarkable decrease in IgA levels, while those with stable or progressive disease displayed an increase in IgA levels after 3 months of treatment. Furthermore, the dynamic alteration in IgA levels after 3 months of treatment demonstrated predictive value for both progression-free survival (PFS) and overall survival (OS). The time-dependent receiver operating characteristic curves exhibited outstanding performance in predicting PFS (AUC 0.793) and OS (AUC 0.738). CONCLUSION: Taken together, this study demonstrates that dynamic alteration of serum IgA after 3 months of treatment was significantly correlated with prognosis and therapeutic efficacy in mccRCC patients.

Artemisia annua L. polysaccharide improves the growth performance and intestinal barrier function of broilers challenged with Escherichia coli.

With the high intensification of poultry breeding, a series of diseases caused by pathogenic bacteria threaten the health of poultry and human. Among them, poultry diseases induced by Escherichia coli cause significant economic loss every year. The aim of this study was to investigate the effects of dietary supplementation with Artemisia annua L. polysaccharide (AAP) on the growth performance and intestinal barrier function of broilers with Escherichia coli (E. coli) challenge. A total of 256 one-day-old chicks were randomly assigned to four treatment groups: control group (fed basal diet), AAP group (fed basal diet supplemented with AAP), E. coli group (fed basal diet and orally administered E. coli), AAP + E. coli group (fed basal diet supplemented with AAP and orally administered E. coli). Dietary AAP supplementation elevated the BW, ADG and ADFI in non-challenged broilers. AAP also increased the apparent metabolic rate of EE and Ca in E. coli-challenged broilers. Moreover, AAP not only enhanced the serum IgA content but also decreased the serum and jejunum content of IL-6, as well as the jejunum level of IL-1ß in non-challenged broilers. AAP also down-regulates the mRNA level of inflammatory factors (IL-1ß, IL-6, and TNF-α) by inhibiting the mRNA expression of TLR4 and MyD88 in intestinal NF-κB signaling pathway of E. coli-challenged broilers. Meanwhile, AAP up-regulates the activity and mRNA level CAT by down-regulating the mRNA level of Keap1 in intestinal Nrf2 signaling pathway of E. coli-challenged broilers, and decreased serum MDA concentration. AAP significantly elevated the mRNA level of CAT, SOD and Nrf2 in jejunal of non-challenged broilers. Interestingly, AAP can improve intestinal physical barrier by down-regulating serum ET content, increasing the jejunal villus height/crypt depth (VH/CD) and ZO-1 mRNA level in broilers challenged by E. coli. AAP also elevated the VH/CD and the mRNA level of Occludin, ZO-1, Mucin-2 in non-challenged broilers. Importantly, AAP reshaped the balance of jejunum microbiota in E. coli-challenged broilers by altering α diversity and community composition. In summary, AAP ameliorated the loss of growth performance in broilers challenged with E. coli, probably by regulating the intestinal permeability and mucosa morphology, immune function, antioxidant ability, and microbiota.

Secondary metabolites with fungicide potentials from the deep-sea seamount-derived fungus Talaromyces scorteus AS-242.

Marine natural products play an important role in biopesticides. Seven new secondary metabolites with different structural classes, including two cycloheptapeptides, scortide A (1) and scortide B (2), two 19-nor-diterpenoids, talascortene H (3) and talascortene I (4), two diterpenoid acids, talascortene J (5) and talascortene K (6), and one triterpenoid, talascortene L (7) were isolated and identified from the sea-anemone-derived endozoic fungus Talaromyces scorteus AS-242. Their structures were comprehensively assigned by spectroscopic data analysis, single-crystal X-ray diffraction, tandem mass spectrometry, and electronic circular dichroism (ECD) calculations. The result of the antimicrobial assay demonstrated that compounds 1 - 6 have inhibitory activity against several human, aquatic, and plant pathogens with minimum inhibitory concentration (MIC) values ranging from 1 to 64 µg/mL. Specially, compounds 2 and 4 showed significant activities against the pathogenic fungus Curvularia spicifera with the MIC value of 1 µg/mL, providing an experimental basis of 2 and 4 with the potential as lead compounds to be developed into biopesticides.