Anti-bacterial effects, and metabolites derived from bifidobacterial fermentation of an exopolysaccharide of Cs-HK1 medicinal fungus.

This study was to investigate the antibacterial effects and metabolites derived from bifidobacterial fermentation of an exopolysaccharide EPS-LM produced by a medicinal fungus Cordyceps sinensis, Cs-HK1. EPS-LM was a partially purified polysaccharide fraction which was mainly composed of Man, Glc and Gal at 7.31:12.95:1.00 mol ratio with a maximum molecular weight of 360 kDa. After fermentation of EPS-LM in two bifidobacterial cultures, B. breve and B. longum, the culture digesta showed significant antibacterial activities, inhibiting the proliferation and biofilm formation of Escherichia coli. Based on untargeted metabolomic profiling of the digesta, the levels of short chain fatty acids, carboxylic acids, benzenoids and their derivatives were all increased significantly (p < 0.01), which probably contributed to the enhanced antibacterial activity by EPS-LM. Since EPS-LM was only slightly consumed for the bifidobacterial growth, it mainly stimulated the biosynthesis of bioactive metabolites in the bifidobacterial cells. The results also suggested that EPS-LM polysaccharide may have a regulatory function on the bifidobacterial metabolism leading to production of antibacterial metabolites, which may be of significance for further exploration.

Inverted U-Shaped relationship Between Systemic Immune-Inflammation Index and Pulmonary Function: A Large Population-Based Study in US Adults.

Background: Systemic immune-inflammation index (SII) is a novel comprehensive inflammatory marker. Inflammation is associated with impaired lung function. We aimed to explore the possible relationship between SII and lung function to examine the potential of SII in predicting lung function decline. Methods: A cross-sectional survey was conducted using the data of the NHANES from 2007 to 2012. Multiple linear regression models were used to analyze the linear relationship between SII and pulmonary functions. Sensitivity analyses, subgroup analyses, and interaction tests were used to examine the robustness of this relationship across populations. Fitted smooth curves and threshold effect analysis were used to describe the nonlinear relationships. Results: A total of 10,125 patients were included in this study. After adjusting for all covariates, multiple linear regression model analysis showed that high Log2-SII level was significantly associated with decreased FVC(ß, -23.4061; 95% CI, -42.2805- -4.5317), FEV1(ß, -46.7730; 95% CI, -63.3371- -30.2089), FEV1%(ß, -0.7923; 95% CI, -1.1635- -0.4211), FEV1/FVC(ß, -0.6366; 95% CI, -0.8328- -0.4404) and PEF(ß, -121.4468; 95% CI,-164.1939- -78.6998). The negative correlation between Log2-SII and pulmonary function indexes remained stable in trend test and stratified analysis. Inverted U-shaped relationships between Log2-SII and FVC, FEV1, FEV1%, and PEF were observed, while a negative linear correlation existed between FEV1/FVC and Log2-SII. The cutoff values of the nonlinear relationship between Log2-SII and FVC, FEV1, FEV1%, PEF were 8.3736, 8.0688, 8.3745, and 8.5255, respectively. When SII exceeded the critical value, the lung function decreased significantly. Conclusion: This study found a close correlation between SII and pulmonary function indicators. This study investigated the SII threshold when lung functions began to decline in the overall population. SII may become a promising serological indicator for predicting lung function decline. However, prospective studies were needed further to establish the causal relationship between these two factors.

Identification of genomic alteration and prognosis using pathomics-based artificial intelligence in oral leukoplakia and head and neck squamous cell carcinoma: A multicenter experimental study.

BACKGROUND: Loss of chromosome 9p is an important biomarker in the malignant transformation of oral leukoplakia (OLK) to head and neck squamous cell carcinoma (HNSCC), and is associated with the prognosis of HNSCC patients. However, various challenges have prevented 9p loss from being assessed in clinical practice. The objective of this study was to develop a pathomics-based artificial intelligence (AI) model for the rapid and cost-effective prediction of 9p loss (9PLP). MATERIALS AND METHODS: 333 OLK cases were retrospectively collected with hematoxylin and eosin (H&E)-stained whole slide images and genomic alteration data from multicenter cohorts to develop the genomic alteration prediction AI model. They were divided into a training dataset (n=217), a validation dataset (n=93), and an external testing dataset (n=23). The latest Transformer method and XGBoost algorithm were combined to develop the 9PLP model. The AI model was further applied and validated in two multicenter HNSCC datasets (n=42, n=365, respectively). Moreover, the combination of 9PLP with clinicopathological parameters was used to develop a nomogram model for assessing HNSCC patient prognosis. RESULTS: 9PLP could predict chromosome 9p loss rapidly and effectively using both OLK and HNSCC images, with the area under the curve achieving 0.890 and 0.825, respectively. Furthermore, the predictive model showed high accuracy in HNSCC patient prognosis assessment (the area under the curve was 0.739 for 1-year prediction, 0.705 for 3-year prediction, and 0.691 for 5-year prediction). CONCLUSION: To the best of our knowledge, this study developed the first genomic alteration prediction deep learning model in OLK and HNSCC. This novel AI model could predict 9p loss and assess patient prognosis by identifying pathomics features in H&E-stained images with good performance. In the future, the 9PLP model may potentially contribute to better clinical management of OLK and HNSCC.

Network pharmacology screening, in vitro and in vivo evaluation of antianxiety and antidepressant drug-food analogue.

BACKGROUND: Depression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties. PURPOSE: This study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs. STUDY DESIGN: Screening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments. METHODS: Utilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations. RESULTS: Ten medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes. CONCLUSION: Our formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue.

CD248-expressing cancer-associated fibroblasts induce non-small cell lung cancer metastasis via Hippo pathway-mediated extracellular matrix stiffness.

Metastasis is a crucial stage in tumour progression, and cancer-associated fibroblasts (CAFs) support metastasis through their participation in extracellular matrix (ECM) stiffness. CD248 is a possible biomarker for non-small cell lung cancer (NSCLC)-derived CAFs, but its role in mediating ECM stiffness to promote NSCLC metastasis is unknown. We investigated the significance of CD248+ CAFs in activating the Hippo axis and promoting connective tissue growth factor (CTGF) expression, which affects the stromal collagen I environment and improves ECM stiffness, thereby facilitating NSCLC metastasis. In this study, we found that higher levels of CD248 in CAFs induced the formation of collagen I, which in turn increased extracellular matrix stiffness, thereby enabling NSCLC cell infiltration and migration. Hippo axis activation by CD248+ CAFs induces CTGF expression, which facilitates the formation of the collagen I milieu in the stromal matrix. In a tumour lung metastasis model utilizing fibroblast-specific CD248 gene knockout mice, CD248 gene knockout mice showed a significantly reduced ability to develop tumour lung metastasis compared to that of WT mice. Our findings demonstrate that CD248+ CAFs activate the Hippo pathway, thereby inducing CTGF expression, which in turn facilitates the collagen I milieu of the stromal matrix, which promotes NSCLC metastasis.

Facile Preparation and Study of Self-healing Water-absorbing Expanding Elastomers.

The absorbent expansion elastomer plays a crucial role in engineering sealing and holds a promising future in this field as infrastructure continues to develop. Traditional materials have their limitations, especially when used in large construction projects where the integrity and reliability of the material are of utmost importance. In this work, a self-healing water-absorbing expansion elastomer was developed for continuous production at a large scale to monitor the sealing conditions of massive infrastructure projects. At room temperature, the material exhibited a repairing efficiency of 57.77% within 2 h, which increased to 84.02% after 12 h. This extended reaction time allowed for effective repairs when defects were detected. The material's strength reached approximately 3 MPa, making it suitable for a wide range of applications. The volume expansion rate of the material reached 200-400% for effective sealing, and the fictionalization of the packing made it have a good external force sensing effect and prevent heat build-up effect. The conductive detection performance of the absorbent expansion elastomer was improved by utilizing triple self-healing strategies, including dipole-dipole interaction, ion cross-linked network, and externally-aided restoration materials.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Association of angiogenesis-associated genes with atherosclerotic plaque progression, intraplaque hemorrhage, and immune infiltration.

Mounting evidence suggests that intraplaque angiogenesis is associated with the progression of atherosclerotic plaques and the development of intraplaque hemorrhage. The specificity of intraplaque immune cell infiltration may be associated with abnormalities in the structure and function of the nascent capillaries. Here, we analyzed expression levels of angiogenesis-associated genes in early and advanced carotid atheromatous plaque tissues as well as in stable and intraplaque hemorrhage plaques. Expression profiles of advanced arterial plaques based on angiogenesis-associated genes were classified into subtypes by performing a consensus clustering analysis. The correlation between the immune microenvironment of plaques and expression of angiogenesis-associated genes was also explored using the single sample gene set enrichment analysis method and the CIBERSORT algorithm. We identified hub angiogenesis-associated genes showing similar expression patterns throughout plaque adverse progression, and constructed a prediction model using the random forest algorithm. Receiver operating curves were constructed to evaluate efficacy in identification of intraplaque hemorrhage in a plaque. Our results suggest that heterogeneity of angiogenesis-related genes may promote the malignant development of plaques and cause plaque rupture. In conclusion, we propose a model based on expression of angiogenesis-related genes to predict the risk of plaque rupture.

Effects of potassium diformate on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora in Cherry Valley ducks.

This study was performed to investigate the effects of potassium diformate (KDF) on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora of Cherry Valley ducks. In total, 144 female healthy 1-day-old Cherry Valley ducks were divided into 3 groups with 6 replicates per group and 8 ducks per replicate according to the principle of similar body weight. The control group was fed a basic diet. In the 2 experimental groups, 0.8% and 1.2% KDF was added to the basic diet, respectively. The trial period was 6 wk and the pretrial period was 3 wk. The final weight and ADG were significantly higher in the 0.8% KDF group than in the control group (P < 0.05). The feed-to-gain ratio was significantly lower in both KDF groups than in the control group (P < 0.05). The apparent digestibility of CP was significantly higher in both KDF groups than in the control group (P < 0.05). The apparent digestibility of calcium was also significantly higher in the 0.8% KDF group (P < 0.05). The serum levels of alkaline phosphatase, cholesterol, and total protein were significantly lower in the 0.8% KDF group than in the control group (P < 0.05), the IgM content was significantly higher (P < 0.05), the low-density lipoprotein cholesterol, triglyceride, and urea levels were significantly lower (P < 0.01), and the glucose level was significantly higher (P < 0.01). The serum total protein level was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of Firmicutes and Patescibacteria in the gut of ducks was significantly higher in the 0.8% KDF group than in the control group (P < 0.05), the relative abundance of unclassified Erysipelotrichaceae and Lactobacillus was significantly higher (P < 0.01), and the relative abundance of Fusobacteriota was significantly lower (P < 0.05). However, the relative abundance of Firmicutes in the gut of ducks was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of unclassified Erysipelotrichaceae and Clostridium sensu stricto 1 was significantly higher (P < 0.01), as was the relative abundance of Fusobacteriota and Proteobacteria (P < 0.05). These findings indicate that the addition of 0.8% KDF to the diet can improve the growth performance of Cherry Valley ducks, promote the absorption of nutrients, change the structure of the microflora in the cecum, and increase the relative abundance of dominant bacteria. It was also shown that there was a significant difference between the 0.8% and 1.2% KDF levels which suggest that the safety margin for overdosing is quite low.

Rational Design of Oil-Resistant and Electrically Conductive Fluorosilicone Rubber Foam Nanocomposites for Sensitive Detectability in Complex Solvent Environments.

Recent years have witnessed the explosive development of highly sensitive smart sensors based on conductive polymer foam materials. However, the design and development of multifunctional polymeric foam composites as smart sensors applied in complex solvent and oil environments remain a critical challenge. Herein, we design and synthesize vinyl-terminated polytrifluoropropylmethylsiloxane through anionic ring-opening polymerization to fabricate fluorosilicone rubber foam (FSiRF) materials with nanoscale wrinkled surfaces and reactive Si-H groups via a green and rapid chemical foaming strategy. Based on the strong adhesion between FSiRF materials and consecutive oxidized ketjen black (OKB) nano-network, multifunctional FSiRF nanocomposites were prepared by a dip-coating strategy followed by fluoroalkylsilane modification. The optimized F-OKB@FSiRF nanocomposites exhibit outstanding mechanical flexibility in wide-temperature range (100 cycle compressions from -20 to 200 °C), structure stability (no detached particles after being immersed into various aqueous solutions for up to 15 days), surface superhydrophobicity (water contact angle of 154° and sliding angle of ∼7°), and tunable electrical conductivity (from 10-5 to 10-2 S m-1). Additionally, benefiting from the combined actions of multiple lines of defense (low surface energy groups, physical barriers, and "shielding effect"), the F-OKB@FSiRF sensor presents excellent anti-swelling property and high sensitivity in monitoring both large-deformation and tiny vibrations generated by knocking the beaker, ultrasonic action, agitating, and sinking objects in weak-polar or nonpolar solvents. This work conceivably provides a chemical strategy for the fabrication of multifunctional polymeric foam nanocomposite materials as smart sensors for broad applications.

Curcumin Inhibits the Development of Pancreatic Cancer by Targeting the circ_0079440/miR-522-3p/EIF4A1 Pathway.

Pancreatic cancer (PC) is a common gastrointestinal cancer with high invasiveness and high mortality. Curcumin is a natural polyphenol with anti-tumor activity against different cancers, including PC. Curcumin has been verified to mediate the expression of circular RNAs (circRNAs) to inhibit tumor development. This study aimed to explore the function and regulatory mechanism of curcumin on circ_0079440 in PC. PC cells were treated with different concentrations of curcumin (0, 5, 10 or 15 µM) for 24 h. Gene expression in PC cells and tissues was detected using RT-qPCR. Cell malignant phenotypes were determined by functional assays. The levels of EMT-related proteins were tested using western blot. RNA interaction was determined using RNA pulldown assay, luciferase reporter assay and RIP assay. The results showed that curcumin suppressed cell proliferative, migratory, and invasive capabilities, and weakened epithelial-mesenchymal transition (EMT) in a concentration-dependent way. Circ_0079440 was expressed at a high level in PC and its level was reduced via curcumin administration in PC cells. Rescue assays showed that circ_0079440 overexpression reversed the suppressive effects of curcumin on PC cell malignant phenotypes. Furthermore, in the xenograft mouse models, curcumin treatment inhibited tumor growth and metastasis, and circ_0079440 upregulation reversed the function of curcumin. Additionally, circ_0079440 was revealed to bind to miR-522-3p to upregulate eukaryotic initiation factor 4A1 (EIF4A1) expression in PC cells. EIF4A1 expression was also downregulated by curcumin, and EIF4A1 overexpression abolished the suppressive functions of curcumin. Moreover, EIF4A overexpression or miR-522-3p inhibition counteracted the anti-tumor effects of circ_0079440 depletion on PC development. To sum up, curcumin suppresses PC development by targeting the circ_0079440/miR-522-3p/EIF4A1 pathway, which might provide novel therapeutic targets for treatment of PC.

Construction and Preparation of the Novel ADN/CL-20 Cocrystal via Directional Hydrogen Bonding Design for Turning Hygroscopicity.

Ammonium dinitramide (ADN), as a novel and environmentally friendly oxidizer, has strong hygroscopicity when exposed to high-humidity air, which seriously hinders its application in solid propellants. Modification of oxidizers by cocrystallization is an effective strategy to improve the hygroscopicity of energetic components. In this paper, the theoretical simulation of ADN/CL-20 cocrystals was developed via a directional hydrogen bonding design to establish a cocrystal with improved hygroscopicity. Intermolecular interaction analyses reveal that hydrogen bonds and van der Waals interactions synergistically lead to the formation of cocrystals. The ADN/CL-20 cocrystal was prepared experimentally by the spray drying self-assembly technique, and the corresponding thermal analysis and sensitivity properties were conducted to illustrate the thermal stability and high safety. Furthermore, the critical relative humidity (CRH) measurement was carried out to evaluate the hygroscopicity of the cocrystal, exhibiting a certain degree of antihygroscopic effect with a CRH of 65%. The hydrogen bonds formed between ADN and CL-20 saturate the ammonium ions of ADN, further preventing ADN from absorbing water molecules in the air. The ADN/CL-20 cocrystal has high specific impulse characteristics (Isp: 272.6 s). Accordingly, this work clearly demonstrates that the ADN/CL-20 cocrystal is expected to be used in a solid propellant to make up for the deficiency of the ADN oxidizer.

Transcriptome combined with single cell to explore hypoxia-related biomarkers in osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative condition among the elderly on a global scale. Research has demonstrated that hypoxia can promote chondrocyte apoptosis and autophagy leading to OA. Hence, it was vital to screen the hypoxia related biomarkers in OA. We introduced transcriptome data to screen out differentially expressed genes (DEGs) in GSE114007 and GSE57218 (OA samples vs control samples). We performed differential expression analysis in key annotated cell to obtain differentially expressed marker genes at the single-cell level (GSE169454). Venn diagram was executed to identify hypoxia related differentially expressed genes (HR-DEGs) associated with OA. Further, feature genes were obtained through the application of least absolute shrinkage and selection operator (LASSO) regression and the Random Forest (RF) algorithm. Receiver operating characteristic (ROC) and expression level analysis were used to identify hypoxia related biomarkers in OA. We further performed immune infiltration and gene set enrichment analysis (GSEA) based on hypoxia related biomarkers. Finally, we analyzed the expression of biomarkers in single-cell level. We identified 2351 DEGs associated with OA. At the single-cell level, 242 differentially expressed marker genes were obtained. 12 HR-DEGs were retained venn diagram. Subsequently, three hypoxia related biomarkers (ADM, DDIT3 and MAFF) were identified. Moreover, we got 15 significantly different immune cells. Finally, we found a lower expression of ADM, DDIT3 and MAFF in OA group compared to the control group in ECs. Overall, we obtained three hypoxia related biomarkers (ADM, DDIT3 and MAFF) associated with OA, which established a theoretical basis for addressing OA.

Association of apolipoprotein A1 levels with lumbar bone mineral density and ß-CTX in osteoporotic fracture individuals: a cross-sectional investigation.

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis. Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (ß-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and ß-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability. Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (ß = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to ß-CTX (ß = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses. Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

The impact of small intestinal bacterial overgrowth on the efficacy of fecal microbiota transplantation in patients with chronic constipation.

To investigate the impact of Small Intestinal Bacterial Overgrowth (SIBO) on the efficacy of Fecal Microbiota Transplantation (FMT) in patients with chronic constipation, our research team included 218 patients with chronic constipation treated with FMT. Based on the results of the SIBO breath test, the patients were divided into two groups: the constipation with SIBO group (SIBO) and the constipation without SIBO group (non-SIBO). The efficacy of the two groups was evaluated using constipation-related scoring scales. At the same time, feces and small intestinal fluid samples were collected from both groups before and after FMT to compare the changes in the intestinal microbiota through 16S rRNA sequencing. In this study, it was found that the clinical efficacy of FMT in the SIBO group was superior to that in the non-SIBO group. After FMT treatment, both groups showed a significant increase in bowel frequency and improvement in stool characteristics. Abdominal symptoms, rectal symptoms, and defecation symptoms were significantly alleviated (P < 0.05), and patients' quality of life was significantly enhanced (P < 0.05). After FMT, except for the Constipation Assessment Scale scores, other scale scores showed significant differences between the two groups, the SIBO group scoring significantly better than the non-SIBO group (P < 0.05). After FMT, there were minor changes in the colonic microbiota but more substantial changes in the small intestinal microbiota. At baseline, the SIBO group had a higher abundance of Veillonella, and lower abundances of Escherichia-Shigella and Acinetobacter compared to the non-SIBO group. Chronic constipation patients with SIBO have a better response to FMT than those without SIBO. IMPORTANCE: Existing studies have rarely considered the impact of the small intestine's microbial state on the efficacy of fecal microbiota transplantation (FMT), nor have they extensively explored the effect of the small intestine's microbial state on the recovery of colonic motility. Therefore, this study investigates the influence of small intestinal bacterial overgrowth (SIBO) on the efficacy of FMT in treating constipation, specifically the impact of the microbial state of the small intestine on the restoration of colonic homeostasis, and consequently on the recovery of colonic motility.

Behavioral Animal Models and Neural-Circuit Framework of Depressive Disorder.

Depressive disorder is a chronic, recurring, and potentially life-endangering neuropsychiatric disease. According to a report by the World Health Organization, the global population suffering from depression is experiencing a significant annual increase. Despite its prevalence and considerable impact on people, little is known about its pathogenesis. One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression. Furthermore, the neural circuit mechanism of depression induced by various factors is particularly complex. Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression, a comparison between the neural circuits of depression induced by various factors is essential for its treatment. In this review, we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression, aiming to provide a theoretical basis for depression prevention.

Targeting Neuraminidase 4 Attenuates Kidney Fibrosis in Mice.

Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial-to-mesenchymal transition, reduces the production of pro-fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4254-388aa interacts with Yes-associated protein (YAP) at WW2 domain (231-263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3',4'-Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4-dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.

Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer.

BACKGROUND: The development of laparoscopic technology has provided a new choice for surgery of gastric cancer (GC), but the advantages and disadvantages of laparoscopic total gastrectomy (LTG) and laparoscopic-assisted total gastrectomy (LATG) in treatment effect and safety are still controversial. The purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC, and to provide a basis for clinical decision-making. AIM: To compare the efficacy of totally LTG (TLTG) and LATG in the context of radical gastrectomy for GC. Additionally, we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy technique. METHODS: Literature on comparative studies of the above two surgical methods for GC (TLTG group and LATG group) published before September 2022 were searched in the PubMed, Web of Science, Wanfang Database, CNKI, and other Chinese and English databases. In addition, the following search keywords were used: Gastric cancer, total gastrectomy, total laparoscopy, laparoscopy-assisted, esophagojejunal anastomosis, gastric/stomach cancer, total gastrectomy, totally/completely laparoscopic, laparoscopic assisted/laparoscopy assisted/laparoscopically assisted, and esophagojejunostomy/esophagojejunal anastomosis. Review Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. RESULTS: After layer-by-layer screening, 258 pieces of literature were recovered, and 11 of those pieces were eventually included. This resulted in a sample size of 2421 instances, with 1115 cases falling into the TLTG group and 1306 cases into the LATG group. Age or sex differences between the two groups were not statistically significant, according to the meta-analysis, however the average body mass index of the TLTG group was considerably higher than that of the LATG group (P = 0.01). Compared with those in the LATG group, the incision length in the TLTG group was significantly shorter (P < 0.001), the amount of intraoperative blood loss was significantly lower (P = 0.003), the number of lymph nodes removed was significantly greater (P = 0.04), and the time of first postoperative feeding and postoperative hospitalization were also significantly shorter (P = 0.03 and 0.02, respectively). There were no significant differences in tumor size, length of proximal incisal margin, total operation time, anastomotic time, postoperative pain score, postoperative anal exhaust time, postoperative anastomosis-related complications (including anastomotic fistula, anastomotic stenosis, and anastomotic hemorrhage), or overall postoperative complication rate (P > 0.05). CONCLUSION: TLTG and esophagojejunostomy are safe and feasible. Compared with LATG, TLTG has the advantages of less trauma, less bleeding, easier access to lymph nodes, and faster postoperative recovery, and TLTG is also suitable for obese patients.

DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.