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This study demonstrates the feasibility and effectiveness of utilizing native soils as a resource for inocula to produce n-caproate through the chain elongation (CE) platform, offering new insights into anaerobic soil processes. The results reveal that all five of the tested soil types exhibit CE activity when supplied with high concentrations of ethanol and acetate, highlighting the suitability of soil as an ideal source for n-caproate production. Compared with anaerobic sludge and pit mud, the native soil CE system exhibited higher selectivity (60.53%), specificity (82.32%), carbon distribution (60.00%), electron transfer efficiency (165.00%), and conductivity (0.59 ms∙cm−1). Kinetic analysis further confirmed the superiority of soil in terms of a shorter lag time and higher yield. A microbial community analysis indicated a positive correlation between the relative abundances of Pseudomonas, Azotobacter, and Clostridium and n-caproate production. Moreover, metagenomics analysis revealed a higher abundance of functional genes in key microbial species, providing direct insights into the pathways involved in n-caproate formation, including in situ CO2 utilization, ethanol oxidation, fatty acid biosynthesis (FAB), and reverse beta-oxidation (RBO). The numerous functions in FAB and RBO are primarily associated with Pseudomonas, Clostridium, Rhodococcus, Stenotrophomonas, and Geobacter, suggesting that these genera may play roles that are involved or associated with the CE process. Overall, this innovative inoculation strategy offers an efficient microbial source for n-caproate production, underscoring the importance of considering CE activity in anaerobic soil microbial ecology and holding potential for significant economic and environmental benefits through soil consortia exploration.

Abstract Background Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. Methods We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. Results There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P

Abstract Exploring catalytic reaction mechanisms is crucial for understanding chemical processes, optimizing reaction conditions, and developing more effective catalysts. We present a reaction-agnostic framework based on high-throughput deep reinforcement learning with first principles (HDRL-FP) that offers excellent generalizability for investigating catalytic reactions. HDRL-FP introduces a generalizable reinforcement learning representation of catalytic reactions constructed solely from atomic positions, which are subsequently mapped to first-principles-derived potential energy landscapes. By leveraging thousands of simultaneous simulations on a single GPU, HDRL-FP enables rapid convergence to the optimal reaction path at a low cost. Its effectiveness is demonstrated through the studies of hydrogen and nitrogen migration in Haber-Bosch ammonia synthesis on the Fe(111) surface. Our findings reveal that the Langmuir-Hinshelwood mechanism shares the same transition state as the Eley-Rideal mechanism for H migration to NH2, forming ammonia. Furthermore, the reaction path identified herein exhibits a lower energy barrier compared to that through nudged elastic band calculation.

Abstract Background Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China. Results A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus’s adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus. Conclusions This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks.

Abstract Early identification of IDH mutation status is of great significance in clinical therapeutic decision-making in the treatment of glioma. We demonstrate a technological solution to improve the accuracy and reliability of IDH mutation detection by combining MRI-based prediction and a CRISPR-based automatic integrated gene detection system (AIGS). A model was constructed to predict the IDH mutation status using whole slices in MRI scans with a Transformer neural network, and the predictive model achieved accuracies of 0.93, 0.87, and 0.84 using the internal and two external test sets, respectively. Additionally, CRISPR/Cas12a-based AIGS was constructed, and AIGS achieved 100% diagnostic accuracy in terms of IDH detection using both frozen tissue and FFPE samples in one hour. Moreover, the feature attribution of our predictive model was assessed using GradCAM, and the highest correlations with tumor cell percentages in enhancing and IDH-wildtype gliomas were found to have GradCAM importance (0.65 and 0.5, respectively). This MRI-based predictive model could, therefore, guide biopsy for tumor-enriched, which would ensure the veracity and stability of the rapid detection results. The combination of our predictive model and AIGS improved the early determination of IDH mutation status in glioma patients. This combined system of MRI-based prediction and CRISPR/Cas12a-based detection can be used to guide biopsy, resection, and radiation for glioma patients to improve patient outcomes.

This paper explores the use of digital footprints data to improve on the limited information available on the size and distribution of the residential housing stock in the United Kingdom over the past two decades. We use a subset of a large dataset consisting of the names and addresses of more than one billion individuals dating back to 1997 (LCRs: Linked Consumer Registers) to calibrate property lifecycle information within an authoritative geolocated address and property dataset. We validate the results of our novel calibration method against official estimates by the UK government covering the same period. We further show that our calibration method, based on individual level data, captures a much larger share of the residential housing stock since 1997 than would have been possible with other available data sources. We argue that these housing stock estimates are fundamental to the development of a comprehensive digital footprints data infrastructure that has the potential to significantly enhance population, migration, and other social statistics in the UK. More generally, this study highlights the benefits of using digital footprints data in refining, calibrating, and extending existing datasets.

Investigating the influences of different sterilization methods on overall juice quality is essential for the production of high-quality juice. The effects of ultra-high temperature instantaneous sterilization (UHT), thermosonication (TS), high hydrostatic pressure sterilization (HHP), and irradiation sterilization (IS) on the physicochemical properties, functional components, and color of Aronia melanocarpa juice (AMJ) were investigated. In addition, anthocyanin target metabolomics were used to explore the influences of different sterilization methods on the AMJ anthocyanin profile. All sterilization treatments effectively ensured the microbial safety of AMJ, and the AMJ viscosity was noticeably declined after sterilization (p < 0.05). Except for HHP, the other treatments aggravated AMJ browning (p < 0.05). Both TS and HHP treatments significantly enhanced or preserved the total polyphenols, flavonoids, and anthocyanins in AMJ and retained the original juice color, whereas UHT and IS treatments were not conducive to maintaining these characteristics. TS treatment significantly increased cyanidin-3-O-galactoside (C-3-O-gal) and cyanidin-3-O-arabinoside (C-3-O-ara) contents in AMJ by 7.98% and 5.90%, while IS resulted in a significant decrease of 15.74% and 10.46% (p < 0.05). C-3-O-gal and C-3-O-ara were the major reasons for the significant upregulation and downregulation of the total monomeric anthocyanins contents (TMAC) in the AMJ after TS and IS treatment, respectively. Malvidin-3-O-glucoside (M-3-O-glu), Cyanidin-3-O-(6-O-malonyl-β-D-glucoside) and Kaempferol-3-O-rutinoside (K-3-O-rut) might be markers of differential metabolites produced by the TS, HHP, and IS treatments, respectively. Correlation analysis indicated that Cyanidin-3-O-xyloside (C-3-O-xyl), C-3-O-ara, and Pelargonidin-3-O-arabinoside (P-3-O-ara) might be the principal contributed to the antioxidant capacity of AMJ. The research results are anticipated to supply technical reference for AMJ processing.

Abstract Background Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus, contributing to end-stage renal disease with limited treatment options. The development of DKD is attributed to podocyte injury resulting from abnormal podocyte autophagy. Consequently, the restoration of podocyte autophagy is deemed a practicable approach in the treatment of DKD. Methods Diabetic mice were induced by streptozotocin and high-fat diet feeding. Following 8 weeks of “QN” agarwood treatment, metrics such as albuminuria, serum creatinine (Scr), and blood urea nitrogen (BUN) were evaluated. Renal histological lesions were evaluated by H&E, PAS, Masson, and Sirius red staining. Evaluation of the effects of “QN” agarwood on renal inflammation and fibrosis in DKD mice through WB, q-PCR, and IHC staining analysis. Cytoscape 3.7.1 was used to construct a PPI network. With the DAVID server, the gene ontology (GO) functional annotation and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the target enrichment were performed. Molecular docking and binding affinity calculations were conducted using AutoDock, while PyMOL software was employed for visualizing the docking results of active compounds and protein targets. Results The results of this study show that “QN” agarwood reduced albuminuria, Scr, and BUN in DKD mice, and improved the renal pathological process. Additionally, “QN” agarwood was observed to downregulate the mRNA and protein expression levels of pro-inflammatory and pro-fibrotic factors in the kidneys of DKD mice. Network pharmacology predicts that “QN” agarwood modulates the epidermal growth factor receptor (EGFR) signaling pathway. “QN” agarwood can increase the expression of LC3B and Nphs1 in DKD mice while reducing the expression of EGFR. Conclusion The present study demonstrated that “QN” agarwood ameliorated renal injury in DKD by targeting EGFR and restoring podocyte autophagy. Graphical Abstract

Abstract Background With the increasing prevalence of colorectal cancer (CRC), optimizing perioperative management is of paramount importance. This study investigates the potential of stellate ganglion block (SGB), known for its stress response-mediating effects, in improving postoperative recovery. We postulate that preoperative SGB may enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. Methods We conducted a randomized controlled trial of 57 patients undergoing laparoscopic colorectal cancer surgery at a single center. Patients, aged 18–70 years, were randomly assigned to receive either preoperative SGB or standard care. SGB group patients received 10 mL of 0.2% ropivacaine under ultrasound guidance prior to surgery. Primary outcome was time to flatus, with secondary outcomes encompassing time to defecation, lying in bed time, visual analog scale (VAS) pain score, hospital stays, patient costs, intraoperative and postoperative complications, and 3-year mortality. A per-protocol analysis was used. Results Twenty-nine patients in the SGB group and 28 patients in the control group were analyzed. The SGB group exhibited a significantly shorter time to flatus (mean [SD] hour, 20.52 [9.18] vs. 27.93 [11.69]; p = 0.012), accompanied by decreased plasma cortisol levels (mean [SD], postoperatively, 4.01 [3.42] vs 7.75 [3.13], p = 0.02). Notably, postoperative pain was effectively managed, evident by lower VAS scores at 6 h post-surgery in SGB-treated patients (mean [SD], 4.70 [0.91] vs 5.35 [1.32]; p = 0.040). Furthermore, patients in the SGB group experienced reduced hospital stay length (mean [SD], day, 6.61 [1.57] vs 8.72 [5.13], p = 0.042). Conclusions Preoperative SGB emerges as a promising approach to enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. Clinical trial registration ChiCTR1900028404, Principal investigator: Xia Feng, Date of registration: 12/20/2019.

Background: Hepatocellular carcinoma (HCC) is among the most prevalent digestive system malignancies and is associated with a poor prognosis. Necroptosis, a form of regulated death mediated by death receptors, exhibits characteristics of both necrosis and apoptosis. Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in tumor necroptosis. This study aims to identify the necroptosis-related lncRNAs (np-lncRNA) in HCC and investigate their relationships with prognosis. Method: The RNA-sequencing data, along with clinicopathological and survival information of HCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The np-lncRNAs were analyzed to assess their potential in predicting HCC prognosis. Prognostic signatures related to necroptosis were constructed using stepwise multivariate Cox regression analysis. The prognosis of patients was compared using Kaplan-Meier (KM) analysis. The accuracy of the prognostic signature was evaluated using Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Quantitative real-time polymerase chain reaction(qPCR) was employed to validate the lncRNAs expression levels of lncRNAs among samples from an independent cohort. Results: The np-lncRNAs ZFPM2-AS1, AC099850.3, BACE1-AS, KDM4A-AS1 and MKLN1-AS were identified as potential prognostic biomarkers. The prognostic signature constructed from these np-lncRNAs achieved an Area Under the Curve (AUC) of 0.773. Based on the risk score derived from the signature, patients were divided into two groups, with the high-risk group exhibiting poorer overall survival. Gene Set Enrichment Analysis (GSEA) revealed significantly different between the low risk and high risk groups in tumor-related pathways (such as mTOR, MAPK and p53 signaling pathways) and immune-related functions (like T cell receptor signaling pathway and natural killer cell mediated cytotoxicity). The increased expression of np-lncRNAs was confirmed in another independent HCC cohort. Conclusions: This signature offers a dependable method for forecasting the prognosis of HCC patients. Our findings indicate a subset of np-lncRNA biomarkers that could be utilized for prognosis prediction and personalized treatment strategies of HCC patients.

Wolfberry, esteemed as a traditional Chinese medicinal material and functional food, is replete with nutrients and boasts a diverse array of health benefits, including hypoglycemic, antitumor, antioxidant, anti-inflammatory, and immune-enhancing properties. Notably, inflammation is a pivotal factor in the onset and progression of numerous diseases. Despite this, there is a paucity of research on the comprehensive evaluation of the components found in different wolfberries, and the exploration of their primary active components is limited. To address this issue, we conducted a comprehensive targeted metabolomics analysis, employing statistical methods such as principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), KEGG pathway analysis, and volcano plots to delineate the compositional differences among red, black, and yellow wolfberries. Furthermore, we investigated the anti-inflammatory effects of their primary components through in vitro experiments. Our analysis revealed a total of 1,104 chemical compositions in the three wolfberries, with alkaloids, phenolic acids, flavonoids, and lipids being the predominant nutritional components. KEGG enrichment analysis indicated that these compositions were primarily involved in the biosynthesis of secondary metabolites, ABC transport, and galactose metabolism pathway. Moreover, our study demonstrated that quercetin exhibited dose-dependent anti-inflammatory activity in LPS-stimulated HUVECs. It effectively inhibited the production of inflammatory factors such as TNF-α, MCP-1, and IL-1β, while also down-regulating the gene and protein expression levels of ICAM-1 and VCAM-1. In conclusion, our findings indicate that there are variations in compositions among the three wolfberries, with flavonoids being the most abundant, and in vitro studies also confirmed the anti-inflammatory potential of quercetin. It is worth noting that Lycium ruthenicum contains higher levels of antioxidant components and possesses greater nutritional value, providing valuable insights for the future development and utilization of the three wolfberries.

BackgroundObservational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood.MethodsA bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran’s Q statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy.ResultsIn forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032–1.250, p = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086–1.477, p = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630–0.833, p < 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823–0.969, p = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28− CD127− CD25++ CD8+ T cell AC, CD28− CD25++ CD8+ T cell AC, CD28− CD8+ T cell/CD8+ T cell, CD28− CD8+ T cell AC, and CD45 RA− CD28− CD8+ T cell AC.ConclusionOur study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC.

This study investigated the storage characteristics of probiotic fermented kiwifruit juice under 4 ℃ refrigeration. The research focused on the changes in the viable lactic acid bacteria count physicochemical properties, sensory quality, nutritional quality and functional properties of the juice during 14 days storage period. Additionally, preliminary shelf-life prediction was made based on the changes in ascorbic acid during the storage. The results showed that the fermented kiwifruit juice maintained good probiotic activity throughout the entire storage process with a consistently higher viable bacterial count of over 8.7 lg CFU/mL. Meanwhile, the fermented juice maintained stable physicochemical properties and color and odor characteristics during storage. Compared to unfermented juice, probiotic fermentation contributed to retaining and maintaining ascorbic acid, total phenols and antioxidant activity of juice during storage. In particular, the unfermented juice experienced a 67.98% loss in ascorbic acid after storage, while fermented juice only lost 23.94%. Moreover, based on the zero-order kinetic model, the study effectively predicted the changes in ascorbic acid in kiwifruit juice during storage. The prediction results indicated that fermented juice could be stored at 4 ℃ for 50 d, while unfermented juice could only be stored for 15 d, based on whether ascorbic acid could be effectively supplemented. This showed that fermented kiwifruit juice could maintain high nutritional quality for an extended period during cold storage, further providing the possibility for the commercialization of fermented kiwifruit juice.

Abstract Background The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta‐analysis. Methods Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO‐FC), six‐minute walk distance (6MWD), N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2), were included. Results Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20 m, 95% CI: 10.74–37.67), NT‐proBNP (SMD: −0.41, 95% CI: −0.79–0.04), CI (MD: 0.47 L/min/m2, 95% CI: 0.17–0.77) and WHO‐FC (OR: 0.564, 95% CI: 0.457–0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30 L/min/m2, 95% CI: 0.15–0.46) and WHO‐FC (OR: 0.589, 95% CI: 0.376–0.922). Within 6 months of treatment, only the WHO‐FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380–0.993; MD: 0.30 L/min/m2, 95% CI: 0.16–0.45, respectively). More than 6 months of treatment significantly improved the 6MWD, WHO‐FC and NT‐proBNP (MD: 40.87 m, 95% CI: 10.97–70.77; OR: 0.557, 95% CI: 0.440–0.705; SMD: −0.61, 95% CI: −1.17–0.05, respectively). Conclusions Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6 months, selexipag exerted obvious effects, even in the low‐dosage group. This finding is important for guiding individualized treatments.

Abstract Traditional Chinese medicine (TCM) has been widely used for several centuries for metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). At present, NAFLD has become the most prevalent form of chronic liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. However, there is still a lack of effective treatment strategies in Western medicine. The development of NAFLD is driven by multiple mechanisms, including genetic factors, insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, gut microbiota dysbiosis, and adipose tissue dysfunction. Currently, certain drugs, including insulin sensitizers, statins, vitamin E, ursodeoxycholic acid and betaine, are proven to be beneficial for the clinical treatment of NAFLD. Due to its complex pathogenesis, personalized medicine that integrates various mechanisms may provide better benefits to patients with NAFLD. The holistic view and syndrome differentiation of TCM have advantages in treating NAFLD, which are similar to the principles of personalized medicine. In TCM, NAFLD is primarily classified into five types based on clinical experience. It is located in the liver and is closely related to spleen and kidney functions. However, due to the multi-component characteristics of traditional Chinese medicine, its application in the treatment of NAFLD has been considerably limited. In this review, we summarize the advances in the pathogenesis and treatment of NAFLD, drawn from both the Western medicine and TCM perspectives. We highlight that Chinese and Western medicine have complementary advantages and should receive increased attention in the prevention and treatment of NAFLD.

Digital transformation has become an inevitable choice for enterprises to survive and compete. This article aims to investigate mechanisms and impacts of peer effects in digital transformation within supply chain networks. Using a sample of listed companies in China from 2011 to 2020, the findings suggest the existence of peer effects in the digital transformation of enterprises within supply chain networks. These effects become more significant as the perception of uncertainty and environmental uncertainty increase. Further analysis reveals that the greater the disparity in discourse power and the degree of digital transformation among peer enterprises within the supply chain, the stronger the peer effects. The study also examines various scenarios in which enterprises operate, finding that greater supply chain stability significantly enhances the peer effects of digital transformation. Heterogeneity tests indicate that peer effects in digital transformation are more evident when peer enterprises within the supply chain are located in different regions, operate in different industries, are non-state-owned, have directorial connections and common institutional ownership, and possess fluctuating executive teams. Additionally, the study discusses the spillover effects of digitalization among peer enterprises on the focal company. This research provides a micro-level exploration of the peer effects of digital transformation from a supply chain perspective, offering theoretical references and practical insights for enterprises seeking to achieve digital transformation.

This study presents a novel massively high-throughput reinforcement learning (RL) framework specifically designed for addressing classic control problems, leveraging our proposed architecture and algorithms optimized for efficient concurrent computations on GPUs. Our research demonstrates the effectiveness of our methods in efficiently training RL agents across various classic control problems, encompassing both discrete and continuous domains, while achieving rapid and stable performance up to 10K concurrent environment instances. Furthermore, we observe that RL exploration with a large number of parallel instances significantly enhances the stability of updating a shared model. For instance, we show that the stability of Deep Deterministic Policy Gradient (DDPG) training can be achieved without requiring experience replay, as evidenced in our study.

Abstract Objective Tobacco has been identified as a significant contributory element to the development of breast cancer. Our objective was to evaluate the spatiotemporal trends of tobacco-related breast cancer at the global, regional, and national scales during 1990–2019. Methods We extracted data on mortality, disability adjusted of life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) from the Global Burden of Disease (GBD) study 2019. Estimated annual percentage change (EAPC) was computed to assess the temporal change in ASDR and ASMR. Results In 2019, the deaths and DALYs attributed to tobacco-related breast cancer were estimated to be 35,439 (95% UI: 22,179–48,119) and 1,060,590 (95% UI: 622,550–1,462,580), respectively. These figures accounted for 5.1% and 5.2% of the total burden of breast cancer. ASMR and ASDR increased in low SDI regions, remained stable in low-middle and middle SDI regions and declined in high and high-middle SDI regions. The burden of breast cancer attributable to tobacco varied notably among regions and nations. Oceania, Southern Latin America, and Central Europe were the GBD regions with the highest number of ASMR and DALYs. There was a positive relationship between age-standardized rate and SDI value in 2019 across 204 nations or territories. A negative association was observed between the EAPC in ASMR or ASDR and the human development index (HDI) in 2019 (R = -0.55, p

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction (DMED) a challenging endeavor. Notable factors contributing to DMED include oxidative stress, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway activation, and apoptosis, while nitro-oleic acid (NO2-OA) has been shown to be beneficial in treating these aspects of this condition. We, herein, investigated the effects and possible mechanisms of NO2-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes. Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group. However, in response to 4 weeks of NO2-OA treatment, there was an improvement in erectile function. The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group. The expression of proapoptotic factors was increased, while that of antiapoptotic factors was decreased in the DMED group. Moreover, the cell morphology in the cavernous tissue of the DMED group also changed adversely. NO2-OA treatment significantly reversed all these changes observed in the DMED group. In conclusion, NO2-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress, activation of the NO/cGMP pathway, and a reduction in apoptosis.

Abstract Background Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. Methods We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. Results A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3–5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2–27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P

Objectives: Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss.Methods: We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes.Results: Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis.Discussion: Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.

Kiwi starch (KS) is a new fruit-derived starch-based food material. In this study, wheat flour was partially replaced with 10–20% KS to make bread, and the influence of this substitution on mixed flour, dough processing performance, bread quality, and shelf life was investigated. KS substitution improved the water-binding ability of mixed flour, making it easier to gelatinize while improving viscoelasticity but reducing the integrity of the dough's gluten network structure. As the substitution rate increases, the hardness, air-cell ratio, and width-to-height ratio of bread significantly increased, while the springiness, resilience, baking loss, and specific volume reduced significantly (p

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized for its global prevalence and potential progression to more severe liver diseases such as non-alcoholic steatohepatitis (NASH). The primary treatment for NASH is modifying lifestyle through dietary or exercise interventions. The aim of the current study is to investigate the roles of Fufang Zhenzhu Tiaozhi polysaccharides (FTZPs) in mice with NASH. FTZPs were concurrently administered to high-fat diet (HFD)-induced 24-week NASH model mice. FTZPs treatment effectively improved liver lipid metabolism, reduced inflammation and fibrosis, improved the integrity of the intestinal mucosal barrier, and modulated the structure of the intestinal microbiota. FTZPs treatment significantly reduced the abundance of Gammaproteobacteria, Clostridium, and Coprococcus while as induced the abundance of Dehalobacteraceae and Dehalobacterium. Furthermore, sixteen differential metabolites were screened by metabolomics, and the change of asparagine was the most significant. In addition, the correlation analysis showed that there was a significant correlation between asparagine and the aforementioned differential bacteria. The present study demonstrated that FTZPs, as the fundamental pharmacological elements of FTZ (Fufang Zhenzhu Tiaozhi), protect against NASH by improving intestinal barrier damage and regulating intestinal flora with the increase in asparagine.

This review focuses on changes in nutrition and functional properties of protein-rich foods, primarily attributed to alterations in protein structures. We provide a comprehensive overview and comparison of commonly used laboratory methods for protein structure identification, aiming to offer readers a convenient understanding of these techniques. The review covers a range of detection technologies employed in food protein analysis and conducts an extensive comparison to identify the most suitable method for various proteins. While these techniques offer distinct advantages for protein structure determination, the inherent complexity of food matrices presents ongoing challenges. Further research is necessary to develop and enhance more robust detection methods to improve accuracy in protein conformation and structure analysis.

Canine circovirus (CanineCV), which is a new mammalian circovirus first reported in the United States in 2012, mainly causes diarrhea and vomiting in dogs. As CanineCV evolves and new subtypes emerge, there is an urgent need for new detection technologies to improve the sensitivity and detection rates of viruses in complex scenarios. A chip digital PCR(cdPCR) assay was established for the detection of CanineCV in this study. The results showed good reproducibility, specificity and a linear relationship; the minimum detection limit of CanineCV by cdPCR was 6.62 copies/μL, which is 10 times more sensitive than quantitative real-time PCR (qPCR). The qPCR-positive detection rate was 1 %, while CanineCV cdPCR (2.1 %) exhibited a greater positive detection rate. Fifteen complete genomes were sequenced and subdivided into CanineCV-1 and CanineCV-3. In conclusion, we developed a rapid, reliable, and specific cdPCR method for screening and monitoring canine CV.