Chiral kagome superconductivity modulations with residual Fermi arcs.

Superconductivity involving finite-momentum pairing1 can lead to spatial-gap and pair-density modulations, as well as Bogoliubov Fermi states within the superconducting gap. However, the experimental realization of their intertwined relations has been challenging. Here we detect chiral kagome superconductivity modulations with residual Fermi arcs in KV3Sb5 and CsV3Sb5 using normal and Josephson scanning tunnelling microscopy down to 30 millikelvin with a resolved electronic energy difference at the microelectronvolt level. We observe a U-shaped superconducting gap with flat residual in-gap states. This gap shows chiral 2a × 2a spatial modulations with magnetic-field-tunable chirality, which align with the chiral 2a × 2a pair-density modulations observed through Josephson tunnelling. These findings demonstrate a chiral pair density wave (PDW) that breaks time-reversal symmetry. Quasiparticle interference imaging of the in-gap zero-energy states reveals segmented arcs, with high-temperature data linking them to parts of the reconstructed vanadium d-orbital states within the charge order. The detected residual Fermi arcs can be explained by the partial suppression of these d-orbital states through an interorbital 2a × 2a PDW and thus serve as candidate Bogoliubov Fermi states. In addition, we differentiate the observed PDW order from impurity-induced gap modulations. Our observations not only uncover a chiral PDW order with orbital selectivity but also show the fundamental space-momentum correspondence inherent in finite-momentum-paired superconductivity.

Functional activities of three Rehmannia glutinosa enzymes: Elucidation of the Rehmannia glutinosa salidroside biosynthesis pathway in Saccharomyces cerevisiae.

Rehmannia glutinosa produces many phenylethanoid glycoside (PhG) compounds, including salidroside, which not only possesses various biological activities but also is a core precursor of some medicinal PhGs, so it is very important to elucidate the species' salidroside biosynthesis pathway to enhance the production of salidroside and its derivations. Although some plant copper-containing amine oxidases (CuAOs), phenylacetaldehyde reductases (PARs) and UDP-glucose glucosyltransferases (UGTs) are thought to be vital catalytic enzymes involved in the downstream salidroside biosynthesis pathways, to date, none of these proteins or the associated genes in R. glutinosa have been characterized. To verify a postulated R. glutinosa salidroside biosynthetic pathway starting from tyrosine, this study identified and characterized a set of R. glutinosa genes encoding RgCuAO, RgPAR and RgUGT enzymes for salidroside biosynthesis. The functional activities of these proteins were tested in vitro by heterologous expression of these genes in Escherichia coli, confirming these catalytic abilities in these corresponding reaction steps of the biosynthetic pathway. Importantly, four enzyme-encoding genes (including the previously reported RgTyDC2 encoding tyrosine decarboxylase and the RgCuAO1, RgPAR1 and RgUGT2 genes) were cointegrated into Saccharomyces cerevisiae to reconstitute the R. glutinosa salidroside biosynthetic pathway, achieving an engineered strain that produced salidroside and validating these enzymes' catalytic functions. This study elucidates the complete R. glutinosa salidroside biosynthesis pathway from tyrosine metabolism in S. cerevisiae, establishing a basic platform for the efficient production of salidroside and its derivatives.

Sludge bound-EPS solubilization enhance CH4 bioconversion and membrane fouling mitigation in electrochemical anaerobic membrane bioreactor: Insights from continuous operation and interpretable machine learning algorithms.

Bound extracellular polymeric substances (EPS) are complex, high-molecular-weight polymer mixtures that play a critical role in pore clogging, foulants adhesion, and fouling layer formation during membrane filtration, owing to their adhesive properties and gelation tendencies. In this study, a novel electrochemical anaerobic membrane bioreactor (EC-AnMBR) was constructed to investigate the effect of sludge bound-EPS solubilization on methane bioconversion and membrane fouling mitigation. During the 150-days' operation, the EC-AnMBR demonstrated remarkable performance, characterized by an exceptionally low fouling rate (transmembrane pressure (TMP) < 4.0 kPa) and high-quality effluent (COD removal > 98.2 %, protein removal > 97.7 %, and polysaccharide removal > 98.5 %). The highest methane productivity was up to 38.0 ± 3.1 mL/Lreactor/d at the applied voltage of 0.8 V with bound-EPS solubilization, 107.6 % higher than that of the control stage (18.3 ± 2.4 mL/Lreactor/d). Morphological and multiplex fluorescence labeling analyses revealed higher fluorescence intensities of proteins, polysaccharides, total cells and lipids on the surface of the fouling layer. In contrast, the interior exhibited increased compression density and reduced activity, likely attributable to compression effect. Under the synergistic influence of the electric field and bound-EPS solubilization, biomass characteristics exhibited a reduced propensity for membrane fouling. Furthermore, the bio-electrochemical regulation enhanced the electroactivity of microbial aggregates and enriched functional microorganisms, thereby promoting biofilm growth and direct interspecies electron transfer. Additionally, the potential hydrogenotrophic and methylotrophic methanogenesis pathways were enhanced at the cathode and anode surfaces, thereby increasing CH4 productivity. The random forest-based machine learning model analyzed the nonlinear contributions of EPS characteristics on methane productivity and TMP values, achieving R² values of 0.879 and 0.848, respectively. Shapley additive explanations (SHAP) analysis indicated that S-EPSPS and S-EPSPN were the most critical factors affecting CH4 productivity and membrane fouling, respectively. Partial dependence plot analysis further verified the marginal and interaction effects of different EPS layers on these outcomes. By combining continuous operation with interpretable machine learning algorithms, this study unveils the intricate impacts of EPS characteristics on methane productivity and membrane fouling behaviors, and provides new insights into sludge bound-EPS solubilization in EC-AnMBR.

De novo transcriptome analysis identifies RpMYB1 as an activator of anthocyanin biosynthesis in Rehmannia piasezkii.

Rehmannia piasezkii is a kind of medicinal plants, of the Orobanchaceae family, and well known for its large pink or purple corolla. However, no research on the molecular mechanism of flower color formation in R. piasezkii has been conducted so far. In this study, we investigated the transcriptome of root, stem, leaf and corollas of R. piasezkii using transcriptome sequencing technology and assembled 144,582 unigenes. A total of 58 anthocyanin biosynthetic genes were identified in the R. piasezkii transcriptome, fourteen of which were highly correlated with anthocyanin content, especially RpF3H2, RpDFR2, RpANS1, RpANS2 and RpUFGT. Totally, 35 MYB genes with FPKM values greater than 5 were identified in the R. piasezkii transcriptome, including an R2R3 MYB transcriptional factor RpMYB1, which belongs to subgroup 6 of the R2R3 MYB family. Agrobacterium-mediated transient expression of Nicotiana benthamiana revealed that overexpression of RpMYB1 could activate the expression of structural genes in anthocyanin synthesis pathway and promote the accumulation of anthocyanins in N. benthamiana leaves, indicating that RpMYB1 is a positive regulator of anthocyanin synthesis. Furthermore, combined transient overexpression of RpMYB1 with RpANS1, RpMYB1+RpANS1 with other structural genes all could further enhance the accumulation of anthocyanins in N. benthamiana leaves. Permanent overexpression of RpMYB1 in R. glutinosa promoted anthocyanin accumulation and expression levels of RgCHS, RgF3H, RgDFR and RgANS. Further evidence from dual-luciferase assay suggested that RpMYB1 could bind to the promoter of RpDFR2 and hence activating its expression. These findings provide insight into the molecular regulation in anthocyanin biosynthesis in R. piasezkii and provide valuable genetic resources for the genetic improvement of flower color.

Progress on the effects and underlying mechanisms of evodiamine in digestive system diseases, and its toxicity: A systematic review and meta-analysis.

BACKGROUND: Evodiamine (EVO) is one of the primary components of Evodia rutaecarpa and has been found to have a positive therapeutic effect on various digestive system diseases. However, no systematic review has been conducted on the research progress and mechanisms of EVO in relation to digestive system diseases, and its toxicity. PURPOSE: This study aimed to provide a reference for future research in this field. STUDY DESIGN: A systematic review and meta-analysis of the research progress, mechanisms, and toxicity of EVO in the treatment of digestive system diseases. METHODS: Five electronic databases were utilized to search for relevant experiments. We conducted a comprehensive review and meta-analysis of the pertinent literature following the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). RESULTS: EVO's animal experiments in digestive system diseases primarily focus on colorectal cancer, gastric ulcers, liver cancer, liver fibrosis, ulcerative colitis, colitis-associated cancer, and functional gastrointestinal disorders. EVO also has positive effects on pancreatic cancer, radiation enteritis, gastric cancer, tongue squamous cancer, hepatitis B, oral cancer, and esophageal cancer in vivo. EVO's in cellular experiments primarily focus on SGC7901, HT29, HCT-116, and HepG2 cells. EVO also exhibits positive effects on SW480, LoVo, BGC-823, AGS, COLO-205, MKN45, SMMC-7721, Bel-7402, QGY7-701, PANC-1, SW1990, BxPC-3, HSC4, MC3, HONE1, and CNE1 cells in vitro. The potential common pathways include TGF-ß, PI3K-AKT, Wnt, ErbB, mTOR, MAPK, HIF-1, NOD-like receptor, NF-κB, VEGF, JAK-STAT, AMPK, Toll-like receptor, EGFR, Ras, TNF, AGE-RAGE, Relaxin, FoxO, IL-17, Hippo, and cAMP. The mechanisms of EVO on ulcerative colitis, gastric cancer, and HCT116 cells are still controversial in vivo. EVO may have a bidirectional regulatory effect on functional gastrointestinal disorders through calcium signaling. The mechanisms of EVO on HCT116, HT29, SW480, AGS, COLO-205, and SW1990 cells are still controversial in vitro. The question of whether EVO has obvious toxicity is controversial. CONCLUSION: In both cellular and animal experiments, EVO has demonstrated positive impacts on digestive system diseases. Nevertheless, additional in vivo and in vitro research is required to confirm the beneficial effects and mechanisms of EVO on digestive system diseases, as well as its potential toxicity.

Crohn's disease in hemophilic arthropathy patient: a case report.

Crohn's disease (CD) is an inflammatory bowel disease affecting the digestive tract, the incidence of which is on the rise worldwide. The most common clinical manifestation of hemophilia is arthropathy secondary to recurrent joint effusions and chronic synovitis. This article reports on a rare 25-year-old male patient with both hemophilic arthropathy and Crohn's disease who was at risk for pathogenic gastrointestinal bleeding. After undergoing endoscopic pathologic testing and genetic testing, a multidisciplinary expert work-up of a treatment and nutritional plan was performed. The patient improved clinically and adhered to conservative treatment. This case report is the first report of this rare co-morbidity, demonstrating the highly pathogenic mutation locus and summarizing the clinical experience of early diagnosis and treatment.

Clinical Efficacy of Intra-articular Tranexamic Acid Injection in the Management of Hemophilia with Total Hip Arthroplasty: A 24-month Retrospective Cohort Study.

OBJECTIVE: Total hip arthroplasty (THA) effectively treats end-stage hemophilic hip arthropathy. Given hemophilia's unique characteristics, perioperative bleeding remains a significant risk for patients undergoing THA. Tranexamic acid (TXA), an efficient antifibrinolytic agent, may benefit the outcomes of THA for patients with hemophilia (PWH). This study aims to explore the clinical efficacy of intra-articular injection of TXA in treating perioperative bleeding in PWH and assess its additional clinical benefits. METHODS: The retrospective study comprised data of PWH who received THA from January 2015 to December 2021 in the research center. A total of 59 individuals were included in the study, divided into a TXA group (n = 31) and a non-TXA group (n = 28). We compared various parameters, including total blood loss (TBL), visible blood loss (VBL), occult blood loss (OBL), intraoperative coagulation factor VIII (FVIII) consumption, perioperative total FVIII consumption, hemoglobin (HB), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), length of hospital stay, hospitalization costs, length of surgery, total protein, activated partial thromboplastin time (APTT), D-dimer, rate of joint swelling, hip joint range of motion (ROM), visual analogue scale (VAS), and Harris hip joint function scale (HHS) between the two groups. Follow-up assessments were conducted for up to 24 months. A Student's t test was utilized for the statistical analysis. RESULTS: This study demonstrated that intra-articular TXA effectively reduced TBL (1248.19 ± 439.88 mL, p < 0.001), VBL (490.32 ± 344.34 mL, p = 0.003), and OBL (757.87 ± 381.48 mL, p = 0.004) in PWH who underwent THA. TXA demonstrated effectiveness in reducing VAS scores on POD1, POD7, and POD14 and joint swelling rates on POD1, POD7, POD14, and at discharge (p < 0.05). Additionally, the TXA group achieved higher HHS ratings at all follow-up time points (p < 0.05), showing superior hip joint mobility, lower postoperative inflammation levels, reduced factor VIII consumption during surgery, and less postoperative nutritional loss. No statistically significant differences were observed between the two groups in terms of hospital stay, hospitalization costs, surgery duration, and coagulation indicators. CONCLUSION: Intra-articular injection of TXA reduces perioperative bleeding in PWH undergoing THA while also improving joint mobility, post-operative rehabilitation, and quality of life. This may provide value for the future application of TXA in PWH.

Integrated multi-omics analysis reveals genes involved in flavonoid biosynthesis and trichome development of Artemisia argyi.

Artemisia argyi is an herbaceous plant of the genus Artemisia. Its young and mature leaves are used as food and medicine, respectively. Glandular trichomes (GTs) are distributed on the leaf surface in A. argyi and are generally considered the location of flavonoid biosynthesis and accumulation. However, the mechanism of flavonoid biosynthesis and accumulation in A. argyi remains unclear. In this study, the coregulatory genes involved in flavonoid biosynthesis and trichome development in this species were screened and evaluated, and the biosynthetic pathways for key flavonoids in A. argyi were uncovered. AaMYB1 and AaYABBY1 were screened using weighted gene co-expression network analysis, and both genes were then genetically transformed into Nicotiana tabacum L. cv. K326 (tobacco). Simultaneously, AaYABBY1 was also genetically transformed into Arabidopsis thaliana. The total flavonoid and rutin contents were increased in tobacco plants overexpressing AaMYB1 and AaYABBY1, and the expression levels of genes participating in the flavonoid synthesis pathway, such as PAL, FLS, and F3H, were significantly up-regulated in plants overexpressing these genes. These results indicated that AaMYB1 and AaYABBY1 promote flavonoid biosynthesis in tobacco. Furthermore, compared to that in the wild-type, the trichome density was significantly increased in tobacco and A. thaliana plants overexpressing AaYABBY1. These results confirm that AaYABBY1 might be involved in regulating trichome formation in A. argyi. This indicates the potential genes involved in and provides new insights into the development of trichome cellular factories based on the "development-metabolism" interaction network and the cultivation of high-quality A. argyi.

Multimode Ultrasound Model for Predicting the Early Treatment Response of Anti-VEGF Agents Plus Anti-PD-1 Antibody in Patients with Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. METHODS: A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. RESULTS: On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. CONCLUSION: Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.

Body Composition in Advanced Non-Small Cell Lung Cancer Treated With Immunotherapy.

Importance: The association between body composition (BC) and cancer outcomes is complex and incompletely understood. Previous research in non-small-cell lung cancer (NSCLC) has been limited to small, single-institution studies and yielded promising, albeit heterogeneous, results. Objectives: To evaluate the association of BC with oncologic outcomes in patients receiving immunotherapy for advanced or metastatic NSCLC. Design, Setting, and Participants: This comprehensive multicohort analysis included clinical data from cohorts receiving treatment at the Dana-Farber Brigham Cancer Center (DFBCC) who received immunotherapy given alone or in combination with chemotherapy and prospectively collected data from the phase 1/2 Study 1108 and the chemotherapy arm of the phase 3 MYSTIC trial. Baseline and follow-up computed tomography (CT) scans were collected and analyzed using deep neural networks for automatic L3 slice selection and body compartment segmentation (skeletal muscle [SM], subcutaneous adipose tissue [SAT], and visceral adipose tissue). Outcomes were compared based on baseline BC measures or their change at the first follow-up scan. The data were analyzed between July 2022 and April 2023. Main Outcomes and Measures: Hazard ratios (HRs) for the association of BC measurements with overall survival (OS) and progression-free survival (PFS). Results: A total of 1791 patients (878 women [49%]) with NSCLC were analyzed, of whom 487 (27.2%) received chemoimmunotherapy at DFBCC (DFBCC-CIO), 825 (46.1%) received ICI monotherapy at DFBCC (DFBCC-IO), 222 (12.4%) were treated with durvalumab monotherapy on Study 1108, and 257 (14.3%) were treated with chemotherapy on MYSTIC; median (IQR) ages were 65 (58-74), 66 (57-71), 65 (26-87), and 63 (30-84) years, respectively. A loss in SM mass, as indicated by a change in the L3 SM area, was associated with worse oncologic outcome across patient groups (HR, 0.59 [95% CI, 0.43-0.81] and 0.61 [95% CI, 0.47-0.79] for OS and PFS, respectively, in DFBCC-CIO; HR, 0.74 [95% CI, 0.60-0.91] for OS in DFBCC-IO; HR, 0.46 [95% CI, 0.33-0.64] and 0.47 [95% CI, 0.34-0.64] for OS and PFS, respectively, in Study 1108; HR, 0.76 [95% CI, 0.61-0.96] for PFS in the MYSTIC trial). This association was most prominent among male patients, with a nonsignificant association among female patients in the MYSTIC trial and DFBCC-CIO cohorts on Kaplan-Meier analysis. An increase of more than 5% in SAT density, as quantified by the average CT attenuation in Hounsfield units of the SAT compartment, was associated with poorer OS in 3 patient cohorts (HR, 0.61 [95% CI, 0.43-0.86] for DFBCC-CIO; HR, 0.62 [95% CI, 0.49-0.79] for DFBCC-IO; and HR, 0.56 [95% CI, 0.40-0.77] for Study 1108). The change in SAT density was also associated with PFS for DFBCC-CIO (HR, 0.73; 95% CI, 0.54-0.97). This was primarily observed in female patients on Kaplan-Meier analysis. Conclusions and Relevance: The results of this multicohort study suggest that loss in SM mass during systemic therapy for NSCLC is a marker of poor outcomes, especially in male patients. SAT density changes are also associated with prognosis, particularly in female patients. Automated CT-derived BC measurements should be considered in determining NSCLC prognosis.

Deep-learning segmentation to select liver parenchyma for categorizing hepatic steatosis on multinational chest CT.

Unenhanced CT scans exhibit high specificity in detecting moderate-to-severe hepatic steatosis. Even though many CTs are scanned from health screening and various diagnostic contexts, their potential for hepatic steatosis detection has largely remained unexplored. The accuracy of previous methodologies has been limited by the inclusion of non-parenchymal liver regions. To overcome this limitation, we present a novel deep-learning (DL) based method tailored for the automatic selection of parenchymal portions in CT images. This innovative method automatically delineates circular regions for effectively detecting hepatic steatosis. We use 1,014 multinational CT images to develop a DL model for segmenting liver and selecting the parenchymal regions. The results demonstrate outstanding performance in both tasks. By excluding non-parenchymal portions, our DL-based method surpasses previous limitations, achieving radiologist-level accuracy in liver attenuation measurements and hepatic steatosis detection. To ensure the reproducibility, we have openly shared 1014 annotated CT images and the DL system codes. Our novel research contributes to the refinement the automated detection methodologies of hepatic steatosis on CT images, enhancing the accuracy and efficiency of healthcare screening processes.

Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study.

Purpose: To explore the effect of AFN on knee function and complications in patients after TKA. Methods: We evaluated 150 patients undergoing unilateral TKA, specifically including 102 patients with varying degrees of AFN after selection. They were divided into four groups based on AFN grade. About 48 patients did not produce AFN, 63 patients were grade I, 29 patients were grade II, and 10 patients were grade III. All patients were followed up for 24 months, and knee function, pain, complications, and other indicators were compared between the four groups. Correlation analysis and regression analysis were used to study the relationship between AFN and other indicators. Results: Two cases of periprosthetic fractures (PPF) occurred in our study, with an incidence of 1.35%, which did not show a significant association with AFN. The changes in knee social score (ΔKSS), Western Ontario and McMaster Universities Osteoarthritis Index (ΔWOMAC), and postoperative anterior knee pain visual analog scale (VAS) score were higher in patients with AFN than in those without. Particularly, grades II and III AFN demonstrated superior efficacy. Pearson's correlation analysis showed that AFN grade is positively correlated with both ΔKSS and ΔWOMAC (r = 0.44, P < 0.001), and AFN grade had a negative correlation with the anterior knee pain VAS (r = -0.250, P < 0.05). In linear regression analysis, AFN grade was positively correlated with both ΔKSS (ß = 5.974, 95% CI: 3.968-7.981, P < 0.001) and ΔWOMAC (ß = 6.356, 95% CI: 4.223-8.490, P < 0.001). Besides that, there was a negative correlation between AFN grade and anterior knee pain (ß = 5.974, 95% CI: 3.968-7.981, P < 0.05). Conclusion: Patients with grade II and III AFN who underwent TKA exhibited better knee function and lower levels of anterior knee pain post-surgery.

Molecular transformation of dissolved organic matter in manganese ore-mediated constructed wetlands for fresh leachate treatment.

The organic matter (OM) and nitrogen in Fresh leachate (FL) from waste compression sites pose environmental and health risks. Even though the constructed wetland (CW) can efficiently remove these pollutants, the molecular-level transformations of dissolved OM (DOM) in FL remain uncertain. This study reports the molecular dynamics of DOM and nitrogen removal during FL treatment in CWs. Two lab-scale vertical-flow CW systems were employed: one using only sand as substrates (act as a control, CW-C) and the other employing an equal mixture of manganese ore powder and sand (experimental, CW-M). Over 488 days of operation, CW-M exhibited significantly higher removal rates for chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), and dissolved organic matter (represented by dissolved organic carbon, DOC) at 98.2 ± 2.5%, 99.2 ± 1.4%, and 97.9 ± 1.9%, respectively, in contrast to CW-C (92.8 ± 6.8%, 77.1 ± 28.1%, and 74.7 ± 9.5%). The three-dimensional fluorescence excitation-emission matrix (3D-EEM) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analyses unveiled that the influent DOM was predominantly composed of readily biodegradable protein-like substances with high carbon content and low unsaturation. Throughout treatment, it led to the degradation of low O/C and high H/C compounds, resulting in the formation of DOM with higher unsaturation and aromaticity, resembling humic-like substances. CW-M showcased a distinct DOM composition, characterized by lower carbon content yet higher unsaturation and aromaticity than CW-C. The study also identified the presence of Gammaproteobacteria, reported as Mn-oxidizing bacteria with significantly higher abundance in the upper and middle layers of CW-M, facilitating manganese cycling and improving DOM removal. Key pathways contributing to DOM removal encompassed adsorption, catalytic oxidation by manganese oxides, and microbial degradation. This study offers novel insights into DOM transformation and removal from FL during CW treatment, which will facilitate better design and enhanced performance.

GPR39 Agonist TC-G 1008 Promoted Mitochondrial Biogenesis and Improved Antioxidative Capability via CREB/PGC-1α Pathway Following Intracerebral Hemorrhage in Mice.

Mitochondrial dysfunction and excessive reactive oxygen species production due to impaired mitochondrial biogenesis have been proven to exacerbate secondary brain injury after intracerebral hemorrhage (ICH). The G-protein-coupled receptor 39 (GPR39) agonist TC-G 1008 has been shown to exert anti-oxidative stress effect in acute hypoxic brain injury. Herein, our study aimed to investigate the potential effects of TC-G 1008 on neuronal mitochondrial biogenesis and antioxidative stress in a mouse model of ICH and explore the underlying mechanisms. A total of 335 male C57/BL6 mice were used to establish an autologous blood-induced ICH model. Three different dosages of TC-G 1008 were administered via oral gavage at 1 h, 25 h, and 49 h post-ICH. The GPR39 siRNA and cAMP response element-binding protein (CREB) inhibitor 666-15 were administered via intracerebroventricular injection before ICH insult to explore the underlying mechanisms. Neurobehavioral function tests, Western blot, quantitative polymerase chain reaction, immunofluorescence staining, Fluoro-Jade C staining, TUNEL staining, dihydroethidium staining, transmission electron microscopy, and enzyme-linked immunosorbent assay were performed. Expression of endogenous GPR39 gradually increased in a time-dependent manner in the peri-hematoma tissues, peaking between 24 and 72 h after ICH. Treatment with TC-G 1008 significantly attenuated brain edema, hematoma size, neuronal degeneration, and neuronal death, as well as improved neurobehavioral deficits at 72 h after ICH. Moreover, TC-G 1008 upregulated the expression of mitochondrial biogenesis-related molecules, including PGC-1α, NRF1, TFAM, and mitochondrial DNA copy number, associated with antioxidative stress markers, such as Nrf2, HO-1, NQO1, SOD, CAT, and GSH-Px. Furthermore, treatment with TC-G 1008 preserved neuronal mitochondrial function and structure post-ICH. Mechanistically, the protective effects of TC-G 1008 on neuronal mitochondrial biogenesis and antioxidative stress were partially reversed by GPR39 siRNA or 666 -15. Our findings indicated that GPR39 agonist TC-G 1008 promoted mitochondrial biogenesis and improved antioxidative capability after ICH, partly through the CREB/PGC-1α signaling pathway. TC-G 1008 may be a potential therapeutic agent for patients with ICH.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Pseudostellaria heterophylla improves intestinal microecology through modulating gut microbiota and metabolites in mice.

BACKGROUND: Pseudostellaria heterophylla is a Chinese medicine and healthy edible that is widely used to for its immunomodulatory, antioxidant, antidiabetic and antitussive properties. However, the potential function of P. heterophylla in intestinal microecology remains unclear. In this study, we investigated the impact of P. heterophylla on immune functions and evaluated its potential to regulate the gut microbiota and metabolome. RESULTS: The results showed that P. heterophylla significantly increased the content of red blood cells, total antioxidant capacity and expression of immune factors, and decreased platelet counts when compared to the control under cyclophosphamide injury. In addition, P. heterophylla altered the diversity and composition of the gut bacterial community; increased the abundance of potentially beneficial Akkermansia, Roseburia, unclassified Clostridiaceae, Mucispirillum, Anaeroplasma and Parabacteroides; and decreased the relative abundance of pathogenic Cupriavidus and Staphylococcus in healthy mice. Metabolomic analyses showed that P. heterophylla significantly increased the content of functional oligosaccharides, common oligosaccharides, vitamins and functional substances. Probiotics and pathogens were regulated by metabolites across 11 pathways in the bacterial-host co-metabolism network. CONCLUSION: We demonstrated that P. heterophylla increased the abundance of probiotics and decreased pathogens, and further stimulated host microbes to produce beneficial secondary metabolites for host health. Our studies highlight the role of P. heterophylla in gut health and provide new insights for the development of traditional Chinese medicine in the diet. © 2024 Society of Chemical Industry.

[Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

A novel nomogram for prediction of intrahepatic recurrence-free survival in patients with HCC followed by radiofrequency ablation.

OBJECTIVE: Although radiofrequency ablation (RFA) has been considered as the favourable treatment option for hepatocellular carcinoma (HCC), there still exist some challenges for new recurrence after RFA. The present study aims to determine the factors affecting recurrence and develop an effective model to predict intrahepatic recurrence-free survival (RFS). METHODS: Patients with HCC followed by RFA between 2000 and 2021 were included in this study. Multivariable Cox regression analysis was used to determine the independent prognostic factors and establish the nomogram predicting intrahepatic RFS after RFA. The predictive performance of the nomogram was assessed according to the C-index, calibration plots, and Kaplan-Meier curves stratified by the tertiles. RESULTS: A total of 801 sessions in 660 patients (including 1155 lesions) were enrolled into this study. Intrahepatic new recurrence was observed in all patients during the follow-up, and the mean intrahepatic RFS was 21.9 months in the present cohort. According to multivariate COX regression analysis, five independent prognostic factors affecting intrahepatic RFS were determined, including age, Child-Pugh class, tumour distribution, number of tumours, and a-fetoprotein (AFP). Based on all independent prognostic factors, the nomogram model was developed and evaluated, which achieved favourable discrimination and calibration. CONCLUSION: This study established five independent prognostic factors and constructed a nomogram model to predict intrahepatic RFS for HCC patients followed by RFA. It could better help clinicians select RFA candidates, as well as offering the important information about whether patients need receive comprehensive treatment to prevent new recurrence after RFA. ADVANCES IN KNOWLEDGE: (1) In this study, 5 preoperative clinic-pathological variables were determined as the independent prognostic factors affecting RFS after RFA in the current largest sample size. (2) Based on these independent prognostic factors, a prognostic nomogram predicting RFS after RFA was established, which may be used to select patients who benefit from RFA and could help both surgeons and patients provide useful information for choosing the personalized treatment.

Radical relay cyclization/C-C bond formation of allyloxy-tethered aryl iodides with quinoxalin-2(1H)-ones via polysulfide anion photocatalysis.

A visible-light-induced radical relay cyclization/C-C bond formation of quinoxalin-2(1H)-ones with allyloxy-tethered aryl iodides using polysulfide anions as a photocatalyst is described. This protocol allows efficient access to a variety of complicated molecules bearing both quinoxalin-2(1H)-one and 2,3-dihydrobenzofuran motifs in high yields under mild reaction conditions with a broad range of substrates.

Extending the Cycle Lifetime of Solid-State Zinc-Air Batteries by Arranging Stable Zinc Species Channels.

The solid-state zinc-air batteries have attracted extensive attention due to their high theoretical energy density, high safety, and the compact structure. In this work, a novel hydrogel solid-state electrolyte was developed that was equipped with an interpenetrating network of zinc polyacrylate (PAZn) and polyacrylamide (PAM). At the same time, a cyclodextrin derivative with sulfonate groups was introduced as an additive. From the design of anionic groups in the network, effective and stable channels for zinc species have been established. The unique structure of the additives regulates the uniform deposition of zinc. After using this solid-state electrolyte, the cycle lifetime of solid-state zinc-air batteries assembled have been significantly extended. The byproducts were greatly suppressed and generated the smooth zinc electrode surface after the charge-discharge cycling.