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Objective To explore the efficacy and safety of intracranial-intracranial bypass for the treatment of complex intracranial aneurysms. Methods and Results A total of 32 patients with complex intracranial aneurysms who were hospitalized for treatment at Huashan Hospital, Fudan University from January 2015 to December 2023 were included. Surgical methods included in-situ bypass, reimplantation, reanastomosis and bypass with interposition graft. For middle cerebral artery (MCA) aneurysms (n = 16), there were 5 cases of in-situ bypass, one case of reimplantation, 3 cases of reanastomosis, and 7 cases of bypass with interposition graft. For anterior cerebral artery (ACA) aneurysms (n = 8), there were 5 cases of in-situ bypass and 3 cases of reimplantation. For anterior communicating artery (ACoA) aneurysms (n = 2), both cases were in-situ bypass. For posterior circulation aneurysms (n = 6), there were 3 cases of in-situ bypass, 2 cases of reanastomosis, and one case of bypass with interposition graft. The intraoperative graft vessels patency rate was 100%. Among the 23 patients who participated in follow-up imaging for more than 6 months postoperatively, no obvious recurrence was indicated by imaging. Among the 28 patients who participated in modified Rankin Scale (mRS) follow-up, there was one case of 5, 5 cases of 3, 2 cases of 2, one case of 1, and 19 cases of 0. Postoperative hemorrhagic complications occurred in 3 cases (9.37%), and ischemic complications occurred in 10 cases (31.25%), with no patients requiring unplanned secondary surgery for complication treatment. Conclusions Intracranial-intracranial bypass has good efficacy and safety for the treatment of complex intracranial aneurysms and has unique advantages in the microsurgical treatment of complex intracranial aneurysms.

Background: Cereal crops are a primary energy source for humans. Grain size and weight affect both evolutionary fitness and grain yield of cereals. Although studies on gene mining and molecular mechanisms controlling grain size and weight are constantly emerging in cereal crops, only a few systematic reviews on the underlying molecular mechanisms and their breeding applications are available so far. Aim of review: This review provides a general state-of-the-art overview of molecular mechanisms and targeted strategies for improving grain size and weight of cereals as well as insights for future yield-improving biotechnology-assisted breeding. Key scientific concepts of review: In this review, the evolution of research on grain size and weight over the last 20 years is traced based on a bibliometric analysis of 1158 publications and the main signaling pathways and transcriptional factors involved are summarized. In addition, the roles of post-transcriptional regulation and photosynthetic product accumulation affecting grain size and weight in maize and rice are outlined. State-of-the-art strategies for discovering novel genes related to grain size and weight in maize and other cereal crops as well as advanced breeding biotechnology strategies being used for improving yield including marker-assisted selection, genomic selection, transgenic breeding, and genome editing are also discussed.

AbstractContext Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota.Objective This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation.Methods We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD.Results Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD.Conclusion This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.

Abstract Background The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. Methods A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. Results Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). Conclusion In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.

The Western Route of the South-to-North Water Diversion Project is the final link to be constructed for the four-horizontal three-vertical framework of China’s national water network. The adjustable water volume in the water source areas is a focal and challenging issue in the planning and demonstration of the Western Route. This study raised ten questions related to the adjustable water volume in the water source areas of the Western Route from the aspects of water resource background conditions and evolution trends, ecological and socio-economic water demands, scales of reservoirs and water conveyance projects, as well as impacts of water diversion on water resource development and utilization, aquatic ecological environment, hydropower, and navigation in the water source areas and their lower reaches. Based on a distributed hydrological model of the upper reaches of the Yangtze River, a simulation and analysis model for calculating the adjustable water volume in water source areas of the Western Route is established to quantitatively answer the ten questions raised. The main conclusions are as follows. First, under the premise of solely satisfying ecological and socio-economic water demands within and outside the river channels of the water source areas, a plan that combines upper and lower routes presents an average adjustable water volume of 1.59×1010 m³ over multiple years, while a plan for solely constructing a lower route can reach an average adjustable water volume of 1.74×1010 m³ by constructing the Gangtuo Reservoir for coordinated operation. Second, comprehensively considering the impacts of water diversion on water balance, hydropower, and navigation, as well as their acceptability in the water source areas, the adjustable water volume is between 1.22×1010 and 1.26×1010 m³. Third, in the long term, the plan should focus on connecting and integrating the water network in the southwestern region with the main framework and major streams of the national water network of China. This will reduce the impacts of water diversion by the Western Route Project, increase the overall water supply capacity of the project, and promote its adaptability to external conditions such as climate change.

The molecular mechanisms driving the onset and metastasis of prostate cancer remain poorly understood. Actin, under the control of actin-binding proteins (ABPs), plays a crucial role in shaping the cellular cytoskeleton, which in turn supports the morphological alterations in normal cells, as well as the invasive spread of tumor cells. Previous research indicates that ABPs of various types serve distinct functions, and any disruptions in their activities could predispose individuals to prostate cancer. These ABPs are intricately implicated in the initiation and advancement of prostate cancer through a complex array of intracellular processes, such as severing, linking, nucleating, inducing branching, assembling, facilitating actin filament elongation, terminating elongation, and promoting actin molecule aggregation. As such, this review synthesizes existing literature on several ABPs linked to prostate cancer, including cofilin, filamin A, and fascin, with the aim of shedding light on the molecular mechanisms through which ABPs influence prostate cancer development and identifying potential therapeutic targets. Ultimately, this comprehensive examination seeks to contribute to the understanding and management of prostate diseases.

Background/purpose(s)The continuously increasing carbapenem resistance within Enterobacterales and Pseudomonas poses a threat to public health, nevertheless, the molecular characteristics of which in southern China still remain limited. And carbapenemase identification is a key factor in effective early therapy of carbapenem-resistant bacteria infections. We aimed to determine the molecular characteristics of these pathogens and compare commercial combined disc tests (CDTs) with the modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) in detecting and distinguishing carbapenemases using whole genome sequencing (WGS).MethodsA total of 78 Enterobacterales, 30 Pseudomonas were obtained from two tertiary hospitals in southern China. Susceptibility tests were conducted using an automated VITEK2 compact system with confirmation via the Kirby–Bauer method. The WGS was conducted on all clinical isolates and the molecular characteristics were analyzed by screening the whole genome sequences. CDTs with or without cloxacillin, mCIM, and eCIM, were performed and compared by taking WGS results as the benchmark.ResultsA total of 103 carbapenem non-susceptible and 5 carbapenem susceptible bacteria were determined, with Klebsiella pneumoniae (42.7%), Pseudomonas aeruginosa (23.3%) and Escherichia coli (18.4%) being most prevalent. Carbapenemase genes were detected in 58 (56.3%) of the 103 carbapenem-non-susceptible clinical isolates, including 46 NDM, 6 KPC, 3 IMP, 1 IPM+VIM,1NDM+KPC, and 1 OXA-181. Carbapenemase-producing isolates were detected more frequently in Enterobacterales (76.3%). Among K. pneumoniae, the major sequence types were st307 and st11, while among E. coli and P. aeruginosa, the most prevalent ones were st410 and st242 respectively. For carbapenemase detection in Enterobacterales, the mCIM method achieved 100.00% (95% CI, 92.13–100.00%) sensitivity and 94.44% (70.63–99.71%) specificity (kappa, 0.96); for Pseudomonas, detection sensitivity was 100% (5.46–100.00%), and 100% (84.50–100.00%) specificity (kappa, 0.65). Commercial CDT carbapenemase detection sensitivity for Enterobacterales was 96.49% (86.84–99.39%), and 95.24% (74.13–99.75%) specificity (kappa, 0.90); for Pseudomonas, carbapenemase detection sensitivity was 100.00% (5.46–100.00%) and 37.93% (21.30–57.64%) specificity (kappa, 0.04). When cloxacillin testing was added, CDT specificity reached 84.61% (64.27–94.95%).ConclusionThe molecular epidemiology of carbapenem-non-susceptible isolates from pediatric patients in Southern China exhibited distinctive characteristics. Both the mCIM–eCIM combination and CDT methods effectively detected and differentiated carbapenemases among Enterobacterales isolates, and the former performed better than CDT among Pseudomonas.

Summary: The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Autoencoder frameworks have received attention for graph embedding, particularly those utilizing generative adversarial networks (GAN). However, GAN-based frameworks do not fully utilize the original graph information and lack stable updates in the GAN component. To bridge this gap, we propose a dual-adversarial framework for graph embedding that expands mutual information (MI) in positive and negative samples for adversarial training using GAN. We further improve model performance by incorporating reinforcement learning ideas. Our framework includes two variants: a pessimistic adversarial graph autoencoder (PAGAE), and a pessimistic adversarial graph autoencoder with PO loss (PAGAEPO). Essentially, we present a pessimistic module to negative sample generator to boost original discriminator, thereby reinforcing the generator’s ability. Additionally, we designed a PO loss function on discriminator to stabilize the learning process and it will further improve the ability of model. Experimental results show that our models are competitive with state-of-the-art GAEs on benchmark datasets.

Abstract Sparganii Rhizoma-Curcumae Rhizoma (SR-CR) is a classic drug pair for the treatment of castration-resistant prostate cancer (CRPC), but its mechanism has not been clarified. The study aims to elucidate the potential mechanism of SR-CR in the management of CRPC. The present study employed the TCMSP as well as the SwissTargetPrediction platform to retrieve the chemical composition and targets of SR-CR. The therapeutic targets of CRPC were identified through screening the GeneCards, Disgenet, and OMIM databases. Subsequently, the Venny online platform was utilized to identify the shared targets between the SR-CR and CRPC. The shared targets were enrichment analysis using the Bioconductor and Kyoto encyclopedia of genes and genomes (KEGG) databases. The active ingredients and core targets were verified through molecular docking and were validated using PC3 cells in the experimental validation phase. A total of 7 active ingredients and 1126 disease targets were screened from SR-CR, leading to a total of 59 shared targets. Gene Ontology (GO) analysis resulted in 1309 GO entries. KEGG pathways analysis yielded 121 pathways, primarily involving cancer-related signaling pathways. The results from molecular docking revealed stable binding interactions between the core ingredients and the core targets. In vitro cellular assays further demonstrated that SR-CR effectively suppressed the activation of the Prostate cancer signaling pathway in PC3 cells, leading to the inhibition of cell proliferation and promotion of apoptosis. The SR-CR exert therapeutic effects on CRPC by inhibiting cell proliferation and promoting apoptosis through the Prostate cancer signaling pathway.

Abstract Background The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. Results Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids’ deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. Conclusions Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract

Abstract Background Alzheimer’s disease (AD), affecting many elders worldwide, is characterized by A-beta and tau-related cognitive decline. Accumulating evidence suggests that brain iron accumulation is an important characteristic of AD. However, the function and mechanism of the iron-mediated gut-brain axis on AD is still unclear. Methods A Caenorhabditis elegans model with tau-overexpression and a high-Fe diet mouse model of cognitive impairment was used for probiotic function evaluation. With the use of qPCR, and immunoblotting, the probiotic regulated differential expression of AD markers and iron related transporting genes was determined. Colorimetric kits, IHC staining, and immunofluorescence have been performed to explore the probiotic mechanism on the development of gut-brain links and brain iron accumulation. Results In the present study, a high-Fe diet mouse model was used for evaluation in which cognitive impairment, higher A-beta, tau and phosphorylated (p)-tau expression, and dysfunctional phosphate distribution were observed. Considering the close crosstalk between intestine and brain, probiotics were then employed to delay the process of cognitive impairment in the HFe mouse model. Pediococcus acidilactici (PA), but not Bacillus subtilis (BN) administration in HFe-fed mice reduced brain iron accumulation, enhanced global alkaline phosphatase (AP) activity, accelerated dephosphorylation, lowered phosphate levels and increased brain urate production. In addition, because PA regulated cognitive behavior in HFe fed mice, we used the transgenic Caenorhabditis elegans with over-expressed human p-tau for model, and then PA fed worms became more active and longer lived than E.coli fed worms, as well as p-tau was down-regulated. These results suggest that brain iron accumulation influences AD risk proteins and various metabolites. Furthermore, PA was shown to reverse tau-induced pathogenesis via iron transporters and AP-urate interaction. Conclusions PA administration studies demonstrate that PA is an important mediator of tau protein reduction, p-tau expression and neurodegenerative behavior both in Caenorhabditis elegans and iron-overload mice. Finally, our results provide candidates for AP modulation strategies as preventive tools for promoting brain health. Video Abstract

Abstract Past studies have shown that the Gelsolin-like actin-capping protein (CAPG) regulates cell migration and proliferation and is strongly associated with tumor progression. We present the first study of the mechanism of action of CAPG in early gastric cancer (EGC). We demonstrate that CAPG expression is upregulated in gastric cancer (GC) especially EGC. CAPG promotes GC proliferation, migration, invasion, and metastasis in vivo and in vitro. More importantly, CAPG plays a role in GC by involving the Wnt/β-catenin signaling pathway. Our findings suggest that CAPG may function as a novel biomarker for EGC.

ABSTRACT: Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/μL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.

Objective: Prostate cancer, marked by a high incidence and mortality rate, presents a significant challenge, especially in the context of castration-resistant prostate cancer (CRPC) with limited treatment options due to drug resistance. This study aims to explore the anti-tumor effects of Xihuang Pills (XHP) on CRPC, focusing on metabolic reprogramming and the Wnt/β-catenin pathway. Methods: In vitro and in vivo biofunctional assays were employed to assess the efficacy and mechanisms of XHP. Subcutaneous xenografts of PC3 in mice served as an in vivo model to evaluate XHP's anti-tumor activity. Tumor volume, weight, proliferation, and apoptosis were monitored. Various assays, including CCK8, TUNEL assay, QRT-PCR, and Western Blotting, were conducted to measure metabolic reprogramming, proliferation, apoptosis, and cell cycle in prostate cancer cells. RNA-seq analysis predicted XHP's impact on prostate cancer, validating the expression of Wnt/β-catenin-related proteins and mRNA. Additionally, 58 compounds in XHP were identified via LC-MS/MS, and molecular docking analysis connected these compounds to key genes. Results: In vitro and in vivo experiments demonstrated that XHP significantly inhibited CRPC cell viability, induced apoptosis, and suppressed invasion and migration. mRNA sequencing revealed differentially expressed genes, with functional enrichment analysis indicating modulation of key biological processes. XHP treatment downregulated Wnt signaling pathway-related genes, including CCND2, PRKCG, and CCN4. Moreover, XHP effectively inhibited glucose uptake and lactate production, leading to reduced HIF-1α and glycolytic enzymes (GLUT1, HK2, PKM2), suggesting its potential in attenuating the Warburg effect. Molecular docking analysis suggested a plausible interaction between XHP's active compounds and Wnt1 protein, indicating a mechanism through which XHP modulates the Wnt/β-catenin pathway. Conclusion: XHP demonstrated remarkable efficacy in suppressing the growth, proliferation, apoptosis, migration, and invasiveness of prostate tumors. The interaction between XHP's active constituents and Wnt1 was evident, leading to the inhibition of Wnt1 and downstream anti-carcinogenic factors, thereby influencing the β-catenin/HIF-1α-mediated glycolysis.

Abstract As a unique subclass of metal‐organic frameworks (MOFs), MOFs with open metal site (OMS) are demonstrated efficient gas separation performance through pi complexation with unsaturated hydrocarbons. However, their practical application faces the challenge of humidity that causes structure degradation and completive binding at the OMS. In this work, the effect of linker methylation of a copper MOF (BUT‐155) on the C2H2/CO2 separation performance under humid condition is evaluated. The water adsorption isotherm, adsorption kinetics, and breakthrough under dry and humid conditions are performed. The BUT‐155 with methylated linker exhibits lower water uptake and adsorption kinetics under humid condition (RH = 20%), in comparison with HKUST‐1. Therefore, the C2H2/CO2 separation performance of BUT‐155 is much less affected by water, especially under higher gas flow rate. Moreover, the dynamic C2H2/CO2 separation performance of BUT‐155 can maintain five breakthrough cycles under humid conditions (RH = 20% and RH = 80%) without obvious performance degradation.

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12–1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10–1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.