Structural biology of flavivirus NS1 protein and its antibody complexes.

The genus of flavivirus includes many mosquito-borne human pathogens, such as Zika (ZIKV) and the four serotypes of dengue (DENV1-4) viruses, that affect billions of people as evidenced by epidemics and endemicity in many countries and regions in the world. Among the 10 viral proteins encoded by the viral genome, the nonstructural protein 1 (NS1) is the only secreted protein and has been used as a diagnostic biomarker. NS1 has also been an attractive target for its biotherapeutic potential as a vaccine antigen. This review focuses on the recent advances in the structural landscape of the secreted NS1 (sNS1) and its complex with monoclonal antibodies (mAbs). NS1 forms an obligatory dimer, and upon secretion, it has been reported to be hexametric (trimeric dimers) that could dissociate and bind to the epithelial cell membrane. However, high-resolution structural information has been missing about the high-order oligomeric states of sNS1. Several cryoEM studies have since shown that DENV and ZIKV recombinant sNS1 (rsNS1) are in dynamic equilibrium of dimer-tetramer-hexamer states, with tetramer being the predominant form. It was recently revealed that infection-derived sNS1 (isNS1) forms a complex of the NS1 dimer partially embedded in a High-Density Lipoprotein (HDL) particle. Structures of NS1 in complexes with mAbs have also been reported which shed light on their protective roles during infection. The biological significance of the diversity of NS1 oligomeric states remains to be further studied, to inform future research on flaviviral pathogenesis and the development of therapeutics and vaccines. Given the polymorphism of flavivirus NS1 across sample types with variations in antigenicity, we propose a nomenclature to accurately define NS1 based on the localization and origin.

3D printed VEGF-CPO biomaterial scaffold to promote subcutaneous vascularization and survival of transplanted islets for the treatment of diabetes.

Diabetes is a complex metabolic disease and islet transplantation is a promising approach for the treatment of diabetes. Unfortunately, the transplanted islets at the subcutaneous site are also affected by various adverse factors such as poor vascularization and hypoxia. In this study, we utilize biocompatible copolymers l-lactide and D,l-lactide to manufacture a biomaterial scaffold with a mesh-like structure via 3D printing technology, providing a material foundation for encapsulating pancreatic islet cells. The scaffold maintains the sustained release of vascular endothelial growth factor (VEGF) and a slow release of oxygen from calcium peroxide (CPO), thereby regulating the microenvironment for islet survival. This helps to improve insufficient subcutaneous vascularization and reduce islet death due to hypoxia post-transplantation. By pre-implanting VEGF-CPO scaffolds subcutaneously into diabetic rats, a sufficiently vascularized site is formed, thereby ensuring early survival of transplanted islets. In a word, the VEGF-CPO scaffold shows good biocompatibility both in vitro and in vivo, avoids the adverse effects on the implanted islets, and displays promising clinical transformation prospects.

A UDP-glycosyltransferase gene PcUGT202A9 was associated with abamectin resistance in Panonychus citri (McGregor).

Panonychus citri (McGregor) strains have developed a high level of resistance to abamectin, but the underlying molecular mechanism is unknown. Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are critical for the removal of a variety of exogenous and endogenous substances. In this study, an enzyme activity assay revealed that UGTs potentially contribute to P. citri abamectin resistance. Spatiotemporal expression profiles showed that only PcUGT202A9 was significantly overexpressed in the abamectin-resistant strain (AbR) at all developmental stages. Moreover, UGT activity decreased significantly, whereas abamectin susceptibility increased significantly, in AbR after PcUGT202A9 was silenced. Three-dimensional modeling and molecular docking analyses revealed that PcUGT202A9 can bind stably to abamectin. Recombinant PcUGT202A9 activity was detected when α-naphthol was used, but the enzymatic activity was inhibited by abamectin (50 % inhibitory concentration: 803.3 ±â€¯14.20 µmol/L). High-performance liquid chromatography and mass spectrometry analyses indicated that recombinant PcUGT202A9 can effectively degrade abamectin and catalyze the conjugation of UDP-glucose to abamectin. These results imply PcUGT202A9 contributes to P. citri abamectin resistance.

The effect of self-designed metabolic equivalent exercises on cancer-related fatigue in patients with gastric cancer: A randomized controlled trial.

AIMS: To investigate the effect of Self-designed Metabolic Equivalent Exercises (SMEE) on cancer-related fatigue in patients with gastric cancer. METHODS: 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ-C30 Quality of Life Scale were used to measure cancer-caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. RESULTS: After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow-up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ-C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p < 0.001) subscales; in the SMEE group, QLQ-C30 scores in somatic (2.00 ± 0.27 vs. 1.31 ± 0.26, p < 0.001), emotional (2.67 ± 0.58 vs. 2.07 ± 0.48, p < 0.001), and social (3.23 ± 0.58 vs. 1.64 ± 0.51, p < 0.001) functioning were significantly higher than those in the control group, with significant improvements in fatigue (p < 0.001), nausea/vomiting (p = 0.014), shortness of breath (p < 0.001), constipation (p < 0.001), and diarrhea (p = 0.001) dimensions. CONCLUSION: The self-programmed metabolic equivalent manipulation as an exercise intervention could effectively reduce the degree of cancer-caused fatigue and improve quality of life in patients with gastric cancer.

Psychological status and related factors of resident physicians during the release of COVID-19 pandemic restrictions in China.

Background: Resident physicians at the standardized training stage had undergone significant physical and mental stress during the release of the COVID-19 pandemic restrictions at the end of 2022 in China. This study aimed to investigate the psychological status (including anxiety, depression, somatic symptoms, job burnout, and vicarious trauma) of resident physicians and identify its influencing factors under these special periods. Methods: Survey was conducted one month after the release of the COVID-19 pandemic restrictions on resident training physicians from a tertiary first-class hospital in Zhejiang, China. Resident physicians completed the psychological status questionnaire. Chi-square tests, Mann-Whitney U tests, and logistic regression analyses were used to estimate the group differences and variable associations. Results: The prevalence of anxiety, depression, and somatic discomfort in this study was 20.88, 28.53, and 41.47%, respectively. Female resident physicians were more likely to experience somatic symptoms [adjusted odds ratio (OR) = 2.36, 95% confidence interval (CI): 1.33-4.18]. Resident physicians with problem-focused coping styles were less prone to psychological health issues [depression (adjusted OR = 0.92, 95% CI: 0.88-0.96), anxiety (adjusted OR = 0.94, 95% CI: 0.90-0.98), somatic symptoms (adjusted OR = 0.93, 95% CI: 0.89-0.97), job burnout (adjusted OR = 0.91, 95% CI: 0.87-0.96) and vicarious trauma (adjusted OR = 0.94, 95% CI: 0.90-0.98)]. Inversely, resident physicians with emotion-focused coping styles and experienced negative life events were more prone to psychological health issues. Conclusion: Resident training physicians had a high risk of anxiety, depression, and somatic symptoms under the special COVID-19 pandemic restriction release period. Females, with lower training stages, degrees, negative life events, and emotion-focused coping styles had a disadvantaged effect on psychological status. The medical teaching management department needs to monitor and reduce the workload and working hours of resident physicians, ensure sufficient sleep time, and pay attention to the psychological status of resident physicians. By strengthening regular communication and mental health education or intervention, which can help them improve their ability to cope with complex tasks.

Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters.

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, the simultaneous construction of acyclic 1,3-nonadjacent stereocenters via a single catalyst in an enantioselective and diastereoselective manner remains a formidable challenge. Here, we demonstrate the enantioselective and diastereodivergent construction of 1,3-nonadjacent stereocenters through Ni-catalyzed reductive cyclization/cross-coupling of alkene-tethered aryl bromides and α-bromoamides, which represents the major remaining stereochemical challenge of cyclization/difunctionalization of alkenes. Using Ming-Phos as ligand, a diverse set of oxindoles containing 1,3-nonadjacent stereocenters were obtained with high levels of enantio- and diastereoselectivity. Mechanistic experiments and density functional theory calculations indicate that magnesium salt plays a key role in controlling the diastereoselectivity. Furthermore, another set of complementary stereoisomeric products were constructed from the same set of starting materials using Ph-Phox as ligand.

Endosymbionts of citrus leafminer Phyllocnistis citrella Stainton among different citrus orchards in China.

Endosymbionts regulate the behavior of pest species, which could provide insights into their control. The citrus leafminer (Phyllocnistis citrella Stainton) is a widely distributed pest associated with diseases of citrus, especially of young trees. Here, we determined the endosymbiont composition of P. citrella in citrus orchards across China. The resulting dataset comprised average 50,430 high-quality reads for bacterial 16S rRNA V3-V4 regions of endosymbionts from 36 P. citrella larvae sampled from 12 citrus orchards across China. The sequencing depth and sampling size of this dataset were sufficient to reveal most of the endosymbionts of P. citrella. In total, 2,875 bacterial amplicon sequence variants were obtained; taxonomic analysis revealed a total of 372 bacterial genera, most of which were Proteobacteria phylum with Undibacterium being the most abundant genus. This dataset provides the first evidence of P. citrella endosymbionts that could support the development of pest management approaches in citrus orchards.

The chromosome-level genome and functional database accelerate research about biosynthesis of secondary metabolites in Rosa roxburghii.

Rosa roxburghii Tratt, a valuable plant in China with long history, is famous for its fruit. It possesses various secondary metabolites, such as L-ascorbic acid (vitamin C), alkaloids and poly saccharides, which make it a high nutritional and medicinal value. Here we characterized the chromosome-level genome sequence of R. roxburghii, comprising seven pseudo-chromosomes with a total size of 531 Mb and a heterozygosity of 0.25%. We also annotated 45,226 coding gene loci after masking repeat elements. Orthologs for 90.1% of the Complete Single-Copy BUSCOs were found in the R. roxburghii annotation. By aligning with protein sequences from public platform, we annotated 85.89% genes from R. roxburghii. Comparative genomic analysis revealed that R. roxburghii diverged from Rosa chinensis approximately 5.58 to 13.17 million years ago, and no whole-genome duplication event occurred after the divergence from eudicots. To fully utilize this genomic resource, we constructed a genomic database RroFGD with various analysis tools. Otherwise, 69 enzyme genes involved in L-ascorbate biosynthesis were identified and a key enzyme in the biosynthesis of vitamin C, GDH (L-Gal-1-dehydrogenase), is used as an example to introduce the functions of the database. This genome and database will facilitate the future investigations into gene function and molecular breeding in R. roxburghii.

The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution.

Flaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on several low-resolution structures, thus hindering the development of drugs and vaccines against flaviviruses. Here, we revealed that recombinant sNS1 from flaviviruses exists in a dynamic equilibrium of dimer-tetramer-hexamer states. Two DENV4 hexameric NS1 structures and several tetrameric NS1 structures from multiple flaviviruses were solved at atomic resolution by cryo-EM. The stacking of the tetrameric NS1 and hexameric NS1 is facilitated by the hydrophobic ß-roll and connector domains. Additionally, a triacylglycerol molecule located within the central cavity may play a role in stabilizing the hexamer. Based on differentiated interactions between the dimeric NS1, two distinct hexamer models (head-to-head and side-to-side hexamer) and the step-by-step assembly mechanisms of NS1 dimer into hexamer were proposed. We believe that our study sheds light on the understanding of the NS1 oligomerization and contributes to NS1-based therapies.

Dual-responsive nanocarriers for efficient cytosolic protein delivery and CRISPR-Cas9 gene therapy of inflammatory skin disorders.

Developing protein drugs that can target intracellular sites remains a challenge due to their inadequate membrane permeability. Efficient carriers for cytosolic protein delivery are required for protein-based drugs, cancer vaccines, and CRISPR-Cas9 gene therapies. Here, we report a screening process to identify highly efficient materials for cytosolic protein delivery from a library of dual-functionalized polymers bearing both boronate and lipoic acid moieties. Both ligands were found to be crucial for protein binding, endosomal escape, and intracellular protein release. Polymers with higher grafting ratios exhibit remarkable efficacies in cytosolic protein delivery including enzymes, monoclonal antibodies, and Cas9 ribonucleoprotein while preserving their activity. Optimal polymer successfully delivered Cas9 ribonucleoprotein targeting NLRP3 to disrupt NLRP3 inflammasomes in vivo and ameliorate inflammation in a mouse model of psoriasis. Our study presents a promising option for the discovery of highly efficient materials tailored for cytosolic delivery of specific proteins and complexes such as Cas9 ribonucleoprotein.

Unveiling the hidden impact: Subclinical hypercortisolism and its subtle influence on bone health.

In recent years, advancements in imaging technologies have led to an increased detection rate of adrenal incidentalomas (AI), with age demonstrating a significant correlation with their incidence. Among the various forms of functional adrenal incidentalomas, subclinical hypercortisolism (SH) stands out as a predominant subtype. Despite the absence of typical symptoms associated with Cushing's syndrome, both domestic and international research consistently establishes a robust link between SH and diverse metabolic irregularities, including hypertension, lipid metabolism disorders, glucose metabolism abnormalities, and disruptions in bone metabolism. Individuals with SH face an elevated risk of cardiovascular events and mortality, highlighting the clinical significance of addressing this condition. Prolonged exposure to elevated cortisol levels poses a significant threat to bone health, contributing to bone loss, alterations in bone microstructure, and an increased susceptibility to fractures. However, comprehensive reviews addressing bone metabolism changes and associated mechanisms in SH patients are currently lacking. Furthermore, the profound impact of concurrent SH on the overall health of the elderly cannot be overstated. A comprehensive understanding of the skeletal health status in elderly individuals with concomitant SH is imperative. This article aims to fill this gap by offering a detailed review of bone metabolism changes and associated mechanisms in SH patients arising from AI. Additionally, it provides a forward-looking perspective on research concerning skeletal health in elderly individuals with concurrent SH.

DhuFAP: a platform for gene functional analysis in Dendrobium huoshanense.

BACKGROUND: Dendrobium huoshanense, a traditional medicinal and food plant, has a rich history of use. Recently, its genome was decoded, offering valuable insights into gene function. However, there is no comprehensive gene functional analysis platform for D. huoshanense. RESULT: To address this, we created a platform for gene function analysis and comparison in D. huoshanense (DhuFAP). Using 69 RNA-seq samples, we constructed a gene co-expression network and annotated D. huoshanense genes by aligning sequences with public protein databases. Our platform contained tools like Blast, gene set enrichment analysis, heatmap analysis, sequence extraction, and JBrowse. Analysis revealed co-expression of transcription factors (C2H2, GRAS, NAC) with genes encoding key enzymes in alkaloid biosynthesis. We also showcased the reliability and applicability of our platform using Chalcone synthases (CHS). CONCLUSION: DhuFAP ( www.gzybioinformatics.cn/DhuFAP ) and its suite of tools represent an accessible and invaluable resource for researchers, enabling the exploration of functional information pertaining to D. huoshanense genes. This platform stands poised to facilitate significant biological discoveries in this domain.

Ligand Engineering for Mitigating Exciton-Phonon Coupling in Mixed Halide Perovskite Nanocrystals.

The vulnerability of mixed halide perovskite nanocrystals (NCs) remains challenging because of the weak interaction between commonly employed ligands, oleic acid/oleylamine (OAm/OA) and halide anions, coupled with substantial surface phonon energy. Here, we introduce 3-aminopropyltriethoxysilane (APTES) as a capping ligand to modify CsPbBrI2 NCs to enhance the interactions between them. The optical properties have been significantly enhanced, and halide segregation has been suppressed, both of which can be attributed to the reduced phonon energy and exciton-phonon coupling strength. Moreover, these APTES-CsPbBrI2 NCs exhibit a broad color gamut and sustained color stability during long-term operation, indicating their promising potential in display technologies. This work may offer insights into surface engineering to enhance the properties and band stability of mixed halide perovskite NCs.

Phylogenomics of Afrotherian mammals and improved resolution of extant Paenungulata.

Molecular investigations have gathered a diverse set of mammals-predominantly African natives like elephants, hyraxes, and aardvarks-into a clade known as Afrotheria. Nevertheless, the precise phylogenetic relationships among these species remain contentious. Here, we sourced orthologous markers and ultraconserved elements to discern the interordinal connections among Afrotherian mammals. Our phylogenetic analyses bolster the common origin of Afroinsectiphilia and Paenungulata, and propose Afrosoricida as the closer relative to Macroscelidea rather than Tubulidentata, while also challenging the notion of Sirenia and Hyracoidea as sister taxa. The approximately unbiased test and the gene concordance factor uniformly recognized the alliance of Proboscidea with Hyracoidea as the dominant topology within Paenungulata. Investigation into sites with extremly high phylogenetic signal unveiled their potential to intensify conflicts in the Paenungulata topology. Subsequent exploration suggested that incomplete lineage sorting was predominantly responsible for the observed contentious relationships, whereas introgression exerted a subsidiary influence. The divergence times estimated in our study hint at the Cretaceous-Paleogene (K-Pg) extinction event as a catalyst for Afrotherian diversification. Overall, our findings deliver a tentative but insightful overview of Afrotheria phylogeny and divergence, elucidating these relationships through the lens of phylogenomics.

Personalized circulating tumor DNA monitoring improves recurrence surveillance and management after curative resection of colorectal liver metastases: a prospective cohort study.

BACKGROUND: Approximately 60% of patients with colorectal liver metastases (CRLM) experience relapse within 2 years after radical resection, previous studies have proven that repeat local treatment (LT) could prolong survival, however, it is difficult to seize the window for LT due to the lack of a high-sensitive surveillance method. In this study, the authors aim to examine the value of longitudinal circulating tumor DNA (ctDNA) in guiding adjuvant chemotherapy, optimizing clinical surveillance strategy, and thereby improving CRLM outcomes. MATERIALS AND METHODS: The authors conducted a prospective clinical trial using a personalized, tumor-informed ctDNA assay to monitor 60 CRLM patients undergoing resection with curative intent. Formalin-fixed paraffin-embedded tumor samples were collected after surgery. Blood samples were collected before surgery, 30 days after surgery (post-OP), and every third month until relapse or up to 2 years. RESULTS: A total of 394 plasma samples from 60 eligible patients were analyzed, with a median follow-up time of 31.3 months. Landmark analyses revealed that detectable ctDNA at post-OP (HR, 4.8), postadjuvant chemotherapy (HR, 6.0), and end-of-treatment (HR, 5.6) were associated with higher recurrence risk ( P <0.001). Post-OP ctDNA positivity served as the only independent prognostic marker in the multivariant analysis (HR, 5.1; P <0.001). Longitudinal ctDNA analysis identified relapsed patients at both sensitivity and specificity of 100%. Most (75%) patients were found with radiological relapse within 6 months after the first detectable ctDNA with a median lead time of 3.5 months. In relapsed patients, 73.2% had oligometastatic disease and 61% were liver-restricted, of which 72.0% received repeat LTs, and 60.0% achieved a secondary no evidence of disease status. CONCLUSIONS: Longitudinal ctDNA monitoring assists in early prediction of relapse, and thereby improves survival of CRLM patients by increased secondary resection rate and secondary no evidence of disease rate.

Identification and Functional Characterization of an Omega-Class Glutathione S-Transferase Gene PcGSTO1 Associated with Cyetpyrafen Resistance in Panonychus citri (McGregor).

Cyetpyrafen is a recently developed acaricide. The citrus red mite, Panonychus citri (McGregor), has developed significant resistance to cyetpyrafen. However, the molecular mechanism underlying the cyetpyrafen resistance in P. citri remains unclear. Glutathione S-transferases (GSTs) play a critical role in arthropod pesticide resistance. This study showed that GSTs were potentially related to the resistance of P. citri to cyetpyrafen through synergistic experiments and enzyme activity analysis. An omega-family GST gene, PcGSTO1, was significantly up-regulated in the egg, nymph, and adult stages of the cyetpyrafen-resistant strain. Additionally, silencing of PcGSTO1 significantly increased the mortality of P. citri to cyetpyrafen and recombinant PcGSTO1 demonstrated the ability to metabolize cyetpyrafen. Our results indicated that the overexpression of PcGSTO1 is associated with cyetpyrafen resistance in P. citri, and they also provided valuable information for managing resistance in P. citri.

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal. Additionally, ursodeoxycholic acid (UDCA) can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concentration in bile. Despite these treatment options, there are still patients who experience stone recurrence. AIM: To analyze the risk factors for choledocholithiasis recurrence after ERCP retrograde cholangiopancreatography and the effect of UDCA intervention. METHODS: The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People's Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected. According to the post-ERCP treatment plan, 100 patients were classified into UDCA (n = 47) and control (n = 53) groups. We aimed to assess the clinical efficacy and rate of relapse in the two patient populations. We then collected information (basic demographic data, clinical characteristics, and serum biochemical indicators) and determined the factors contributing to relapse using logistic regression analysis. Our secondary goal was to determine the effects of UDCA on liver function after ERCP. RESULTS: Compared to the control group, the UDCA group demonstrated a higher clinical effectiveness rate of 92.45% vs 78.72% (P < 0.05). No significant differences were observed in liver function indices, including total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase, between the two groups before treatment. After treatment, all liver function indices were significantly reduced. Comparing the control vs UDCA groups, the UDCA group exhibited significantly lower levels of all indices (55.39 ± 6.53 vs 77.31 ± 8.52, 32.10 ± 4.62 vs 45.39 ± 5.69, 142.32 ± 14.21 vs 189.63 ± 16.87, 112.52 ± 14.25 vs 149.36 ± 15.36, 122.61 ± 16.00 vs 171.33 ± 22.09, 96.98 ± 10.44 vs 121.35 ± 11.57, respectively, all P < 0.05). The stone recurrence rate was lower in the UDCA group (13.21%) in contrast with the control group (44.68%). Periampullary diverticula (OR: 6.00, 95%CI: 1.69-21.30), maximum stone diameter (OR: 1.69, 95%CI: 1.01-2.85), stone quantity >3 (OR: 4.23, 95%CI: 1.17-15.26), and positive bile culture (OR: 7.61, 95%CI: 2.07-27.91) were independent factors that influenced the relapse of common bile duct stones after ERCP (P < 0.05). Furthermore, postoperative UDCA was identified as a preventive factor (OR: 0.07; 95%CI: 0.08-0.09). CONCLUSION: The intervention effect of UDCA after ERCP for common bile duct stones is adequate, providing new research directions and references for the prevention and treatment of stone recurrence.

Stilbenes-enriched peanut sprouts alleviated physical fatigue via regulating interactions of nutrients-microbiota-metabolites revealed by multi-omics analysis.

In this study, the antifatigue effect and mechanism of peanut sprouts were explored. BALB/c mice divided into three groups (control, dark and UV-C) were respectively supplemented with a normal diet, peanut sprouts (dark germination) added diet and stilbenes-enriched peanut sprouts (UV-C radiated germination) added diet. Results showed that swimming time and levels of blood glucose and antioxidant enzymes significantly increased, while contents of triglyceride and malondialdehyde notably decreased by peanut sprout supplementation. Besides, combined analysis of gut microbiota gene sequencing and targeted metabolomics of fecal metabolites revealed that peanut sprout supplementation up-regulated abundances and metabolic transformations of Catenibacillus, Odoribacter, Prevotellaceae-UCG-001 and Butyricicoccus while it down-regulated the abundance of Parabacteroides. Consequently, contents of sebacic acid, azelaic acid, suberic acid, heptanoic acid, pimelic acid, aminoadipic acid and mono-phenolics notably increased, which were markedly correlated with the antifatigue effect. Compared with the dark group, the swimming time, glutathione peroxidase activity, methylmalonylcarnitine content and abundances of Butyricicoccus, Catenibacillus and Lachnospiraceae NK4A136 were higher in the UV-C group, while opposite results were obtained for the levels of triglyceride, malondialdehyde, alpha-linolenic acid, gamma-linolenic acid, 10Z-heptadecenoic acid and palmitelaidic acid. Overall, peanut sprout supplementation could alleviate fatigue by modulating gut microbiota composition to promote fatty acid oxidation and lysine and stilbene catabolism to increase energy supply and regulate redox balance. UV-C-radiated peanut sprout supplementation could alleviate fatigue more effectively by up-regulating abundances of Butyricicoccus, Catenibacillus and Lachnospiraceae NK4A136 to promote long-chain fatty acid oxidation and catabolism of flavonoids and stilbenes efficiently.