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ObjectiveTo understand the influencing factors of gastric cancer incidence among residents in Henan province, providing a reference for the formulation of local gastric cancer prevention and control strategies. MethodsThrough the Henan Provincial Cancer Registration and Reporting System, 198 gastric cancer patients (141 males and 57 females with a median age of 66 years) newly diagnosed between January 2020 and July 2021 in four counties in the Huaihe River basin were selected as the case group. A 1:2 sex and age matching was performed to select 396 healthy residents from the same or adjacent counties as the control group. A face-to-face interview with a standardized questionnaire developed by a group of domestic researchers, physical examination, salt taste threshold test, and detection of Helicobacter pylori infection were conducted among the participants. Conditional logistic regression models were used to analyze the factors influencing gastric cancer morbidity. ResultsCompared to controls, cases had significantly higher proportions of smoking (57.6% vs. 49.7%), exposure to secondhand smoke (69.2% vs. 60.6%), daily water intake < 1 000 ml (52.0% vs. 33.1%), frequent anger (17.2% vs. 4.5%), poor mood or increased stress in the last 10 years (27.8% vs. 9.3%), preference for salty food (47.0% vs. 28.5%), with a salt taste threshold of 4 (34.8% vs. 24.5%), preference for hot food (36.9% vs. 27.5%), preference for hard food (19.2% vs. 8.8%), preference for spicy food (51.5% vs. 40.7%), occasionally or frequently eating leftovers (70.7% vs. 49.7%), eating or handling moldy food (8.1% vs. 2.5%), eating pickled food more than once a week (21.2% vs. 11.9%), being underweight (11.6% vs. 1.8%), and having a history of gastric disease (54.0% vs. 29.0%) (all P < 0.05), whereas cases had significantly lower proportions of drinking alcohol (11.1% vs. 36.1%), drinking tea (16.2% vs. 25.0%), being physically active three or more days a week (15. 2% vs. 23.7%), walking after meals three or more days per week (34.3% vs. 48.5%), using a water filter at home (26.8% vs. 41.9%), eating regular meals (78.8% vs. 89.4%), eating breakfast every day (86.9% vs. 92.7%), and consuming 10 or more grams of raw garlic or garlic sprouts per day (25.3% vs. 33.8%) (all P < 0.05). Multivariate conditional logistic regression analysis revealed the following risk factors for gastric cancer incidence among residents: exposure to secondhand smoke, frequent anger, poor mood or increased stress in the past 10 years, preference for salty food, preference for hard food, occasional or frequent consumption of leftovers, being underweight, having a history of gastric disease, and family history of gastric cancer; the analysis also revealed the following protective factors against gastric cancer incidence: having an education of junior high school or above, having an annual household income of ≥ 5 000 Chinese yuan per capita, using a water filter at home, and being overweight or obese. ConclusionLifestyle, personality and emotional characteristics, dietary habits, history of gastric diseases, and family history of gastric cancer are the main influencing factors of gastric cancer morbidity among residents in Henan province.

ABSTRACTShrimp is a common cause of food allergies in allergic individuals. The management of patients suffering from shrimp allergy relies on avoidance of the specific food, which compromises nutritional requirements. In this study, fermentation was performed using Lactobacillus to reduce the allergenicity of Litopenaeus vannamei. The optimal fermentation conditions using Lactobacillus helveticus TS6024 were 1% glucose, 30% minced shrimp, 2.5% inoculum level, 3% NaCl, and 60 h of incubation at 37°C, whereas those using Lactobacillus acidophilus 6005 were 2% glucose, 20% minced shrimp, 15% inoculum level, 2% NaCl, and 48 h of incubation at 42°C. Under optimal conditions, Lactobacillus helveticus TS6024 and Lactobacillus acidophilus 6005 fermentation reduced the allergenicity of shrimp by 78.97% and 70.09%, respectively. SDS-PAGE analysis showed that the band intensity of tropomyosin (36KDa) reduced evidently after the selected Lactobacillus fermentation. The hypoallergenic shrimp/shrimp products will provide optimal nutrition with reduced risk of adverse reactions in hypersensitive individuals.

Abstract Background Dexmedetomidine (DEX) has a pharmacological profile that should allow rapid recovery and prevent undesirable outcomes such as pulmonary complications. Methods This large retrospective study compared the beneficial effects of perioperative infusion of DEX with propofol on the postoperative outcome after coronary artery bypass graft surgery. We reviewed patients’ medical notes at Luoyang Central Hospital from 1st January 2012 to 31st December 2019. All continuous variables, if normally distributed, were presented as mean ± SD; Otherwise, the non-normally distributed data and categorical data were presented as median (25-75 IQR) or number (percentage). The Mann-Whitney U test and Chi-square test were used to evaluate the difference of variables between the DEX and propofol groups. Multivariate logistic regression analysis was performed on the main related and differential factors in the perioperative period. Results A total of 1388 patients were included in the study; of those, 557 patients received propofol infusion, and 831 patients received dexmedetomidine. DEX significantly reduced postoperative pulmonary complications compared with propofol, 7.82% vs 13.29%; P

Rosa roxburghii Tratt. is an important commercial horticultural crop endemic to China, which is recognized for its extremely high content of L-ascorbic acid (AsA). To understand the mechanisms underlying AsA overproduction in fruit of R. roxburghii, content levels, accumulation rate, and the expression of genes putatively in the biosynthesis of AsA during fruit development have been characterized. The content of AsA increased with fruit weight during development, and AsA accumulation rate was found to be highest between 60 and 90 days after anthesis (DAA), with approximately 60% of the total amount being accumulated during this period. In vitro incubating analysis of 70DAA fruit flesh tissues confirmed that AsA was synthesized mainly via the L-galactose pathway although L-Gulono-1, 4-lactone was also an effective precursor elevating AsA biosynthesis. Furthermore, in transcript level, AsA content was significantly associated with GDP-L-galactose phosphorylase (RrGGP2) gene expression. Virus-induced RrGGP2 silencing reduced the AsA content in R. roxburghii fruit by 28.9%. Overexpressing RrGGP2 increased AsA content by 8-12-fold in tobacco leaves and 2.33-3.11-fold in tomato fruit, respectively, and it showed enhanced resistance to oxidative stress caused by paraquat in transformed tobacco. These results further justified the importance of RrGGP2 as a major control step to AsA biosynthesis in R. roxburghii fruit.

As a tool for modifying the genome, gene editing technology has developed rapidly in recent years, especially in the past two years. With the emergence of new gene editing technologies, such as transposon editing tools, numerous advancements have been made including precise editing of the genome, double base editing, and pilot editing. This report focuses on the development of gene editing tools in recent years, elaborates the progress made in classic editing tools, base editor and other new editing tools, and provides insights into challenges and opportunities.

Diarrhea is considered to be associated with microbial dysbiosis caused by infection of pathogens but poorly understood. We herein characterized the colonic microbiota of diarrheal early-weaning piglets infected with porcine circovirus type 2 (PCV2) and Campylobacter. Campylobacter infection significantly decreased species richness and Shannon diversity index of colonic microbiota together with a significant increase in the proportion of Campylobacter and Enterobacteriaceae, whereas no significant difference on the above indexes was observed in piglets infected with PCV2 compared with healthy piglets. PCV2 and Campylobacter infection could disturb the homeostasis of colonic microbiota through deterioration of ecological network within microbial community, and specially Campylobacter performed as a module hub in ecological networks. The microbial dysbiosis caused metabolic dysfunction and led to a remarkable reduction in production of short chain fatty acids, following by a higher pH level in colon cavity. Campylobacter infection disturbed the function of colonic tract barrier observed in terms of significant lower relative expression of claudin-1, occluding, and zonula occludens protein-1 genes, and PCV2 infection induced intestinal inflammation together with a higher permeability of colon. Generally, these results suggested that PCV2 and Campylobacter infection could induce microbial dysbiosis and metabolic dysfunction, and cause intestinal disorder, all of which finally were associated to contribute to the diarrhea of early-weaning piglets.

Ascorbic acid (AsA) is the most abundant antioxidant in plants and is an important nutritional index for agricultural products. Some plants, such as Rosa roxburghii Tratt., contain exceptionally high levels of AsA, but are relatively unpalatable. In view of its role in human health, as well as plant growth and development, we examined the effects of two important AsA regulatory genes from R. roxburghii in tomato, with the aim of producing a crop of higher nutritional quality. RrGGP2 and RrDHAR were cloned from R. roxburghii fruit. The overexpression vectors were made using 35S promoters and mediated by Agrobacterium tumefaciens to obtain the overexpression lines. A PCR and qRT-PCR verified that the two genes had been inserted and overexpressed in the tomato leaves and fruits. The results showed that the overexpression of RrGGP2 increased tomato leaf and fruit AsA content by 108.5% and 294.3%, respectively, while the overexpression of RrDHAR increased tomato leaf and fruit AsA content by 183.9% and 179.9%. The overexpression of RrGGP2 and RrDHAR further changed the expression of genes related to AsA metabolism, and the upregulation of one such gene, SlGGP, may have contributed greatly to the increase in AsA. Results here indicate that RrGGP2 contributes more towards fruit AsA accumulation in tomato than RrDHAR.

Recently, the widespread use of antibiotics is becoming a serious worldwide public health challenge, which causes antimicrobial resistance and the occurrence of superbugs. In this context, MnO2 has been proposed as an alternative approach to achieve target antibacterial properties on Streptococcus mutans (S. mutans). This requires a further understanding on how to control and optimize antibacterial properties in these systems. We address this challenge by synthesizing δ-MnO2 nanoflowers doped by magnesium (Mg), sodium (Na), and potassium (K) ions, thus displaying different bandgaps, to evaluate the effect of doping on the bacterial viability of S. mutans. All these samples demonstrated antibacterial activity from the spontaneous generation of reactive oxygen species (ROS) without external illumination, where doped MnO2 can provide free electrons to induce the production of ROS, resulting in the antibacterial activity. Furthermore, it was observed that δ-MnO2 with narrower bandgap displayed a superior ability to inhibit bacteria. The enhancement is mainly attributed to the higher doping levels, which provided more free electrons to generate ROS for antibacterial effects. Moreover, we found that δ-MnO2 was attractive for in vivo applications, because it could nearly be degraded into Mn ions completely following the gradual addition of vitamin C. We believe that our results may provide meaningful insights for the design of inorganic antibacterial nanomaterials.

Species markers can be quickly and accurately assessed using DNA barcoding. We investigated samples from the parrotfish family Scaridae using DNA barcoding in Hainan. A total of 401 DNA barcodes were analyzed, including 51 new barcodes generated from fresh material, based on a 533 bp fragment of the cytochrome c oxidase subunit I (CO I) gene. There were 350 CO I barcode clusters that matched 43 species from the Barcode of Life Data Systems (BOLD) and GenBank databases. The results showed the following average nucleotide compositions for the complete dataset: adenine (A, 22.7%), thymine (T, 29.5%), cytosine (C, 29.5%), and guanine (G, 18.2%). The mean genetic distance between confamilial species was nearly 53-fold greater than that between individuals within the species. In the neighbor-joining tree of CO I sequences, Chlorurus sordidus and C. spilurus clustered together, and all other individuals clustered by species. Our results indicated that DNA barcoding could be used as an effective molecular tool for monitoring, protecting, and managing fisheries, and for elucidating taxonomic problem areas that require further investigation.

Background: Family history may inform individuals that they are at risk of gastric cancer (GC). However, it is too extensive to conduct intensive screening strategies for all individuals with family history of GC instead of average-risk screening. To establish more precise prevention strategies, accurate risk estimates are necessary for individuals with family history of GC. Methods: We searched PubMed, EMBASE and Cochrane for all relevant studies from their inception to May 21, 2020, for cohort and case-control studies investigating the association between family history of GC and its risk. Relative risk (RR) and 95% confidence interval (CI) were pooled from studies using random-effects or fixed effects. Results: The RR of GC was 2.08 (95% CI=1.86-2.34) in individuals with family history of GC according to twenty-nine case-control studies and 1.83 (95%CI=1.67-2.01) from six cohort studies. The increased risk was higher in individuals with sibling history of GC than those with parental history of GC (RR=3.18, 95% CI=2.12-4.79 vs. RR=1.66, 95% CI=1.46-1.89, P=0.021). For individuals with 2 or more first-degree relatives (FDRs) with GC, the RR was 2.81(95% CI=1.89-3.99). Subjects with both family history and Helicobacter pylori (H. pylori) infection confer a higher risk of GC (RR = 4.03, 95%CI=2.46-6.59). Conclusion: The RR of GC among FDRs is lower than in previous studies. However, the risk of GC is markedly increased in individuals having a sibling with GC, more than 2 FDRs with GC. Intensified screening and eradication therapy for H. pylori could be considered for these individuals.

Atherosclerosis is a major pathology for cardiovascular diseases (CVDs). Clinically, the intermittent fasting (IF) has been observed to reduce the risk of CVDs. However, the effect of IF on the development of atherosclerosis has not been fully elucidated. Herein, we determined the protection of IF against high-fat diet–induced atherosclerosis in pro-atherogenic low-density lipoprotein receptor deficient (LDLR-/-) mice and the potentially involved mechanisms. The LDLR-/- mice were scheduled intermittent fasting cycles of 3-day HFD feeding ad libitum and 1 day fasting, while the mice in the control group were continuously fed HFD. The treatment was lasted for 7 weeks (∼12 cycles) or 14 weeks (∼24 cycles). Associated with the reduced total HFD intake, IF substantially reduced lesions in the en face aorta and aortic root sinus. It also increased plaque stability by increasing the smooth muscle cell (SMC)/collagen content and fibrotic cap thickness while reducing macrophage accumulation and necrotic core areas. Mechanistically, IF reduced serum total and LDL cholesterol levels by inhibiting cholesterol synthesis in the liver. Meanwhile, HFD-induced hepatic lipid accumulation was attenuated by IF. Interestingly, circulating Ly6Chigh monocytes but not T cells and serum c-c motif chemokine ligand 2 levels were significantly reduced by IF. Functionally, adhesion of monocytes to the aortic endothelium was decreased by IF via inhibiting VCAM-1 and ICAM-1 expression. Taken together, our study indicates that IF reduces atherosclerosis in LDLR-/- mice by reducing monocyte chemoattraction/adhesion and ameliorating hypercholesterolemia and suggests its potential application for atherosclerosis treatment.

At present, the research and innovation of packaging materials are in a period of rapid development. Starch, a sustainable, low-cost, and abundant polymer, can develop environmentally friendly packaging alternatives, and it possesses outstanding degradability and reproducibility in terms of improving environmental issues and reducing oil resources. However, performance limitations, such as less mechanical strength and lower barrier properties, limit the application of starch in the packaging industry. The properties of starch-based films can be improved by modifying starch, adding reinforcing groups, or blending with other polymers. It is of significance to study starch as an active and intelligent packaging option for prolonging shelf life and monitoring the extent of food deterioration. This paper reviews the development of starch-based films, the current methods to enhance the mechanical and barrier properties of starch-based films, and the latest progress in starch-based activity, intelligent packaging, and food applications. The potential challenges and future development directions of starch-based films in the food industry are also discussed.

OBJECTIVES:The aim of this study was to elucidate the molecular mechanisms by which food-derived casein glycomacropeptide (CGMP) maintains internal homeostasis in the intestinal mucosa and to investigate the effects of CGMP on the intestinal mucosal immunological barrier and related signal transduction pathways. METHODS:In this study, a famoxadone (OXZ)-induced mouse experimental ulcerative colitis (UC) model was built. The experimental UC mice were intragastrically administered milk-derived CGMP for four consecutive days. The molecular mechanisms by which milk-derived CGMP improved and restored the inflammatory status in UC symptoms were elucidated by H&E staining, immunohistochemical staining and western blotting. RESULTS:The results indicated that CGMP (50 mg/(kg bw·d)) could significantly improve morphological injury to intestinal mucosa in OXZ-induced UC mice to the same extent that did sulfasalazine (SASP, 40 mg/(kg bw·d)), a medicine used to treat UC, in the control group. The study found that CGMP could significantly reduce the expression of Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1), Cluster of differentiation 4 (CD4) and Cluster of differentiation 8 (CD8) in the lamina propria of the intestinal mucosa and significantly stimulate the secretion of sIgA to increase intestinal immunity. Furthermore, CGMP was found to be directly involved in inhibiting the MAPK pathway and activating the TGF-β1/Smad signal transduction cascade, which could maintain immunological regulation of the intestinal mucosa and protect the functions of the intestinal mucosal barrier. CONCLUSIONS:This study elucidated the molecular mechanisms by which CGMP maintained homeostasis of the intestinal mucosa and further confirmed its pharmaceutical value as a food-derived functional component with promising potential for further exploration/utilization.

Cucumber is an economically important vegetable crop worldwide. Powdery mildew (PM) is one of the most severe diseases that can affect cucumber crops. There have been several research efforts to isolate PM resistance genes for breeding PM-resistant cucumber. In the present study, we used a chromosome segment substitution line, SSL508-28, which carried PM resistance genes from the donor parent, JIN5-508, through twelve generations of backcrossing with a PM-susceptible inbred line, D8. We performed whole-genome resequencing of SSL508-28 and D8 to identify single nucleotide polymorphisms (SNPs), and insertions and deletions (indels). When compared against the reference genome of the inbred cucumber line 9930, a total of 468,616 SNPs and 67,259 indels were identified in SSL508-28, and 537,352 SNPs and 91,698 indels were identified in D8. Of these, 3,014 non-synonymous SNPs and 226 frameshift indels in SSL508-28, and 3,104 non-synonymous SNPs and 251 frameshift indels in D8, were identified. Bioinformatics analysis of these variations revealed a total of 15,682 SNPs and 6,262 indels between SSL508-28 and D8, among which 120 non-synonymous SNPs and 30 frameshift indels in 94 genes were detected between SSL508-28 and D8. Finally, out of these 94 genes, five resistance genes with nucleotide-binding sites and leucine-rich repeat domains were selected for qRT-PCR analysis. This revealed an upregulation of two transcripts, Csa2M435460.1 and Csa5M579560.1, in SSL508-28. Furthermore, the results of qRT-PCR analysis of these two genes in ten PM resistant and ten PM susceptible cucumber lines showed that when exposed to PM, Csa2M435460.1 and Csa5M579560.1 exhibited a higher expression level of resistant lines than susceptible lines. This indicates that Csa2M435460.1 and Csa5M579560.1 are candidate genes for PM resistance in cucumber. In addition, the non-synonymous SNPs in Csa2M435460.1 and Csa5M579560.1, identified in SSL508-28 and D8, might be the key to high PM-resistance in SSL508-28.

Casein glycomacropeptide (GMP) is known to promote the in vitro growth of Bifidobacteria and Lactobacilli. In this paper, we used conven- tional culture techniques and fluorescent in situ hybridization (FISH) techniques to investigate the effect of casein GMP on mice fecal microbiota. The population structure of the intestinal microbiota, including Lactobacillus, Bifidobacteria, Enterococcus, coliforms and Enterobacteriaceae, was tested and compared. After consecutive administration of casein GMP for 15 days, numbers of Lactobacillus and Bifidobacteria increased significantly (PEnterobacteriaceae and Coliforms decreased significantly (P

Abstract Transplant rejection remains a significant barrier to the long-term success of organ transplantation. Biopsy, although considered the gold standard, is invasive, costly, and unsuitable for routine monitoring. Traditional biomarkers, such as creatinine and troponin, offer limited predictive value owing to their low specificity, and conventional imaging techniques often fail to detect early organ damage, increasing the risk of undiagnosed rejection episodes. Considering these limitations, emerging noninvasive biomarkers and molecular imaging techniques hold promise for the early and accurate detection of transplant rejection, enabling personalized management strategies. This review highlights noninvasive biomarkers that predict, diagnose, and assess transplant prognosis by reflecting graft injury, inflammation, and immune responses. For example, donor-derived cell-free DNA (dd-cfDNA) is highly sensitive in detecting early graft injury, whereas gene expression profiling effectively excludes moderate-to-severe acute rejection (AR). Additionally, microRNA (miRNA) profiling enhances the diagnostic specificity for precise AR detection. Advanced molecular imaging techniques further augment the monitoring of rejection. Fluorescence imaging provides a high spatiotemporal resolution for AR grading, ultrasound offers real-time and portable monitoring, and magnetic resonance delivers high tissue contrast for anatomical assessments. Nuclear imaging modalities such as single photon emission computed tomography and positron emission tomography, enable dynamic visualization of immune responses within transplanted organs. Notably, dd-cfDNA and nuclear medicine imaging have already been integrated into clinical practice, thereby demonstrating the translational potential of these techniques. Unlike previous reviews, this work uniquely synthesizes advancements in both noninvasive biomarkers and molecular imaging, emphasizing their complementary strengths. Biomarkers deliver molecular-level insights, whereas imaging provides spatial and temporal resolution. Together, they create a synergistic framework for comprehensive and precise transplant monitoring. By bridging these domains, this review underscores their individual contributions and collective potential to enhance diagnostic accuracy, improve patient outcomes, and guide future research and clinical applications in transplant medicine.

Background: The senescence of endothelial cells is of great importance involving in atherosclerosis (AS) development. Recent studies have proved the protective role of mesenchymal stem cell-derived extracellular vesicles in AS, herein, we further desired to unvei their potential regulatory mechanisms in endothelial cell senescence. Methods: Senescence induced by H2O2 in primary mouse aortic endothelial cells (MAECs) was evaluated by SA-β-gal staining. Targeted molecule expression was detected by qRT-PCR and Western blotting. The biological functions of MAECs were determined by CCK-8, flow cytometry, transwell, and tube formation assays. Oxidative injury was assessed by LDH, total and lipid ROS, LPO and MDA levels. The proliferation of adipose-derived mesenchymal stem cell (ADSCs) was analyzed by EdU assay. Effect of ADSCs-derived extracellular vesicles (ADSC-EVs) on AS was investigated in HFD-fed ApoE−/− mice. Results: miR-674-5p was up-regulated, while C1q/TNF-related protein 9 (CTRP9) was down-regulated in H2O2-induced senescent MAECs. CTRP9 was demonstrated as a target gene of miR-674-5p. miR-674-5p inhibition restrained senescence, oxidative stress, promoted proliferation, migration, and angiogenesis of H2O2-stimulated MAECs via enhancing CTRP9 expression. Moreover, treatment with ADSC-EVs inhibited H2O2-induced senescence and dysfunction of MAECs through regulating miR-674-5p/CTRP9 axis. In the in vivo AS mouse model, ADSC-EVs combination with miR-674-5p silencing slowed down AS progression via up-regulation of CTRP9. Conclusion: ADSC-EVs repressed endothelial cell senescence and improved dysfunction via promotion of CTRP9 expression upon miR-674-5p deficiency during AS progression, which might provide vital evidence for ADSC-EVs as a promising therapy for AS.

Introduction: Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment of patients with malignant melanoma. However, improving therapeutic efficacy requires identifying drug combinations that elicit durable responses without inducing intolerable toxicity. Within that context, selinexor emerges as a possible combination option that has been shown in preclinical studies to enhance the efficacy of ICI therapy. Methods: In this phase 1b study, we investigated selinexor in combination with pembrolizumab in 25 patients with advanced non-uveal melanoma. Patients received selinexor at a dosage of 60 mg taken orally twice weekly, and pembrolizumab intravenously at a dosage of 200 mg every 3 weeks. Results: Despite the high incidence of adverse events (96%), most treatment-related toxicities were manageable with supportive care and dose reductions. The most common adverse events of any grade were nausea (n = 20; 80%), decreased white blood cell count (n = 15; 60%), vomiting (n = 14; 56%), anemia (n = 12; 48%), fatigue (n = 12; 48%), and decreased platelet count (n = 12; 48%). The 10 patients with treatment-naïve evaluable disease had an objective response rate (ORR) of 70% (n = 7, including three patients with complete response), which was significantly higher than that of the 14 patients with prior anti–programmed cell death protein 1 (anti-PD-1) therapy, whose ORR was 7% (n = 1; p = 0.002). Stable disease was observed in two patients (20%) with treatment-naïve disease and seven patients (50%) with prior anti-PD-1 therapy. Conclusion: Selinexor combined with pembrolizumab showed promising antitumor activity in patients with treatment-naïve metastatic melanoma. The toxicity profile of the combination was consistent with that reported for individual agents, with no additional safety concerns.

Abstract Centromere pairing is crucial for synapsis in meiosis. This study delves into the Skp1-Cullin1-F-box protein (SCF) E3 ubiquitin ligase complex, specifically focusing on F-box protein 47 (FBXO47), in mouse meiosis. Here, we revealed that FBXO47 is localized at the centromere and it regulates centromere pairing cooperatively with SKP1 to ensure proper synapsis in pachynema. The absence of FBXO47 causes defective centromeres, resulting in incomplete centromere pairing, which leads to corruption of SC at centromeric ends and along chromosome axes, triggering premature dissociation of chromosomes and pachytene arrest. FBXO47 deficient pachytene spermatocytes exhibited drastically reduced SKP1 expression at centromeres and chromosomes. Additionally, FBXO47 stabilizes SKP1 by down-regulating its ubiquitination in HEK293T cells. In essence, we propose that FBXO47 collaborates with SKP1 to facilitate centromeric SCF formation in spermatocytes. In summary, we posit that the centromeric SCF E3 ligase complex regulates centromere pairing for pachynema progression in mice.

Abstract The effect of seafloor cold seeps on the biogeochemical cycling of mercury (Hg) remains enigmatic. Here we demonstrate substantial enrichments of mercury and methylmercury, along with the presence of microbes capable of metabolizing mercury in sediments of the Haima cold seep, South China Sea, by analyzing mercury and methylmercury concentrations, mercury isotopic composition analyses and metagenomic analyses of sediment cores. Compared to the reference area, the sediments in the upper sediment column of the active-seep area were 2.4 times enriched in Hg and 10.5 times in methylmercury. The slope of the capital delta ratio of mercury 199 to mercury 201 (Δ199Hg/Δ201Hg) with 1.23 ± 0.10 in the active-seep area indicate the occurrence of dark redox reactions. Genes related to mercury methylation (hgcA), demethylation (merB) and reduction (merA) were phylogenetically associated with several bacterial and archaeal linages. We roughly estimated an additional 2,835 Mg mercury and 9 Mg methylmercury are stored in cold seep globally. In summary, we propose that cold seeps globally function as a previously unrecognized sink for mercury and source for methylmercury in the deep ocean.

Fabry disease (FD) is a systemic disease in which globotriaosylceramide and other naturally occurring glycosphingolipid accumulate in various tissues throughout the body due to mutation of α-galactosidase A (GLA). These induced pluripotent stem cells (iPSCs) were generated from a 10-year-old male patient’s urine carrying the GLA c.1080_1082del Fabry disease mutation. The iPSCs were validated by confirming the pluripotent markers expression, trilineage differentiation capability, normal karyotype and targeted mutation. This resource enables further assessment of the pathophysiological development of Fabry disease and serves as a model to develop drugs for treating Fabry disease.

BackgroundPrimary malignant melanoma (MM) of skin threatens health, especially in the older population, causing a significant risk of early death. The purpose of this study was to establish a diagnostic nomogram to predict the early mortality risk in older patients with primary skin MM and to determine the independent risk factors of cancer-specific early death in such patients.MethodsThe Surveillance, Epidemiology and End Results (SEER) database provided the clinical and pathological characteristics of older patients with primary skin MM from 2000 to 2019. Initially, a 7:3 random assignment was used to place the recruited patients into training and validation cohorts. Then, the independent risk variables of cancer-specific early death in those individuals were determined using univariate and multivariate logistic regression analysis. Those patients’ diagnostic nomograms were constructed using the acquired independent risk variables. Ultimately, the performance of the newly created diagnostic nomogram was verified using calibration curves, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves.ResultsIn this study, 2,615 patients in total were included. Age, histology, liver metastasis, tumor stage, surgery, therapy, and radiation were found to be independent risk factors following statistical analysis, with a special emphasis on early death in older patients with primary skin MM. A diagnostic nomogram for the cancer-specific early death risk was created and validated based on these variables. High agreement was reported between the expected and actual probabilities in the calibration curves. Area under the curves (AUC) of the novel created diagnostic nomogram was greater than that of each independent risk factor, with AUCs for the training and validation cohorts being 0.966 and 0.971, respectively. The nomogram had a high value for its applicability in clinical settings, according to DCA.ConclusionIn older patients with primary skin MM, the current study created a diagnostic nomogram to predict the probability of cancer-specific early death. Because of the nomograms’ good performance, physicians will be better able to identify older patients who are at a high risk of early death and treat them individually to increase their survival benefit.

Introduction: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti–PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance. Methods: This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advancedcancers, including anti–PD-1/PD-L1 treatment-resistant melanoma, and anti–PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The primary objectiveof dose escalation phase Ib was to assess safety, tolerability, and recommended phase II dose. The primary objective of the phase II expansion study was to assess the combination’s antitumor activity, including objective response rate and clinical benefitrate. Results: A total of eight patients (five in phase Ib and three in phase II) were evaluable for adverse events (AEs) at our study site. All eight patients experienced at least grade 1 AE. The most common treatment-related AEs were increased serum aspartate aminotransferase (38%), fatigue (38%), anemia (25%), increased alkaline phosphatase (25%), hyperbilirubinemia(25%), hypocalcemia (25%), and hypoalbuminemia (25%). Most of these AEs were grade 1 or 2. None of the patients experienced grade 4 AEs and no drug-related fatal AEs were reported among the eight patients treated in the study. One (13%) patient had stable disease (SD) (captured as unknown by the study sponsor because the evaluation criteria set per protocol was not met) and three (38%) patients had progressive disease. Four (50%) patients developed clinical disease progression based on investigator evaluation. One patient with pancreatic cancer achieved immune-related SD for 26 months while on the study treatments. Conclusion: The study completed phase Ib dose escalation and phase II. However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored.

BACKGROUND: This article evaluated the current status and focus areas in benign paroxysmal positional vertigo (BPPV) research in the world and to predict the direction of future research. METHODS: Web of Science Core Collection were searched from January 1, 2002, to December 31, 2021. Bibliometric and statistical analysis were conducted to generate the basic information of the publications. RESULTS: A total of 1255 publications were identified, with an increasing trend in the number of annual number of publications from 2019 to 2021. Otology & Neurotology was the most productive journal. Kim J, Kim C, and Lee J from South Korea were the top 3 productive authors. Seoul National University is the most influential institution. The top 5 cited burst keywords include recurrence, osteoporosis, bone mineral density, vitamin D deficiency, and BPPV. CONCLUSION: The annual number of publications would continue to grow. The future research of BPPV will concentrate on osteoporosis and recurrence.

Background: Plant health is directly related to the change in native microbial diversity and changes in soil health have been implicated as one of the main cause of root rot. However, scarce information is present regarding allelopathic relationship of Panax notoginseng root exudates and pathogenic fungi Fusarium oxysporum in a continuous cropping system. Methods: We analyzed P. notoginseng root exudate in the planting soil for three successive years to determine phenolic acid concentration using GC-MS and HPLC followed by effect on the microbial community assembly. Antioxidant enzymes were checked in the roots to confirm possible resistance in P. notoginseng. Results: Total 29 allelochemicals in the planting soil extract was found with highest concentration (10.54 %) of p-hydroxybenzoic acid. The HPLC showing a year-by-year decrease in p-hydroxybenzoic acid content in soil of different planting years, and an increase in population of F. oxysporum. Moreover, community analysis displayed negative correlation with 2.22 mmol. L−1 of p-hydroxybenzoic acid correspond to an 18.1 % population of F. oxysporum. Furthermore, in vitro plate assay indicates that medium dose of p-hydroxybenzoic acid (2.5–5 mmol. L−1) can stimulate the growth of F. oxysporum colonies and the production of macroconidia, as well as cell wall-degrading enzymes. We found that 2–3 mmol. L−1 of p-hydroxybenzoic acid significantly increased the population of F. oxysporum. Conclusion: In conclusion, our study suggested that p-hydroxybenzoic acid have negative effect on the root system and modified the rhizosphere microbiome so that the host plant became more susceptible to root rot disease.

Abstract To improve the interface stability between Li-rich Mn-based oxide cathodes and electrolytes, it is necessary to develop new polymer electrolytes. Here, we report an entanglement association polymer electrolyte (PVFH-PVCA) based on a poly (vinylidene fluoride-co-hexafluoropropylene) (PVFH) matrix and a copolymer stabilizer (PVCA) prepared from acrylonitrile, maleic anhydride, and vinylene carbonate. The entangled structure of the PVFH-PVCA electrolyte imparts excellent mechanical properties and eliminates the stress arising from dendrite growth during cycling and forms a stable interface layer, enabling Li//Li symmetric cells to cycle steadily for more than 4500 h at 8 mA cm−2. The PVCA acts as a stabilizer to promote the formation of an electrochemically robust cathode–electrolyte interphase. It delivers a high specific capacity and excellent cycling stability with 84.7% capacity retention after 400 cycles. Li1.2Mn0.56Ni0.16Co0.08O2/PVFH-PVCA/Li full cell achieved 125 cycles at 1 C (4.8 V cut-off) with a stable discharge capacity of ~2.5 mAh cm−2.

There is growing interest in the use of bio-based materials as viable alternatives to petrochemical-based packaging. However, the practical application of bio-based films is often hampered by their poor barrier and poor mechanical properties. In this context, cellulose nanofibers (CNFs) have attracted considerable attention owing to their exceptional biodegradability, high aspect ratio, and large surface area. The extraction of CNFs from agricultural waste or non-food biomass represents a sustainable approach that can effectively balance cost and environmental impacts. The functionalization of CNFs improves the economics of raw materials and production processes while expanding their applications. This paper reviews recent advances in cellulose nanofibers, including their sources, surface modification, and characterization techniques. Furthermore, we systematically discuss the interactions of CNFs with different composites in the development of functional food films. Finally, we highlight the application of cellulose nanofiber films in food preservation. Due to their environmentally friendly properties, CNFs are a promising alternative to petroleum-based plastics. The aim of this paper is to present the latest discoveries and advances in CNFs while exploring the future prospects for edible food films, thereby encouraging further research and application of CNFs in the field of active food packaging.

Background and aimsTranscatheter tricuspid valve replacement (TTVR) has recently emerged as a novel therapeutic approach for managing severe tricuspid regurgitation (TR). However, surgical tricuspid valve replacement (STVR) continues to be the predominant treatment modality. There are limited comparative data on both procedures. This study aimed to compare clinical and echocardiographic outcomes between patients who underwent mini-thoracotomy transatrial LuX-Valve TTVR and those who underwent STVR.MethodsThis study prospectively collected patients with severe TR who underwent TTVR (n = 29) or isolated STVR (n = 59) at Wuhan Union Hospital from 2019 to 2022. All TTVR patients received the LuX-Valve via a mini-thoracotomy and transatrial approach. The clinical and echocardiographic outcomes were compared at 30-day and one-year follow-ups.ResultsAt baseline, patients with LuX-Valve TTVR had higher surgical risk scores and a greater proportion of right ventricular dysfunction compared with STVR. In the early postoperative period, the STVR group had a greater decrease in right ventricular function. Hospital length of stay (LOS), intensive care unit LOS, total procedure time, and tracheal intubation time were shorter in the TTVR than in the STVR group. The incidence of postoperative paravalvular leaks was higher among patients who underwent TTVR. Compared to the STVR group, the pacemaker implantation rate was lower in the TTVR group. During follow-up, the peak tricuspid valve velocity and mean gradient in the TTVR group were consistently lower than those in the STVR group. There was similar mortality between TTVR and STVR at 30-day and one-year follow-ups.ConclusionsThe mini-thoracotomy transatria LuX-Valve TTVR has a higher incidence of paravalvular leaks and a lower rate of pacemaker implantation than STVR, with similar 30-day and one-year mortality rates. In some respects, mini-thoracotomy transatrial LuX-Valve TTVR may be a feasible and safe treatment option for specific populations, or it could potentially serve as an alternative therapy to supplement conventional STVR. Further follow-up is required to assess differences in long-term clinical outcomes and valve durability.

PurposeThe impact of aortic stenosis (AS) severity on multidirectional myocardial function in patients with bicuspid aortic valve (BAV) remains unclear, despite the recognized presence of early left ventricular longitudinal myocardial dysfunction in BAV patients with normal valve function. The aim of the study was to evaluate the multidirectional myocardial functions of BAV patients.MethodsA total of 86 BAV patients (age 46.71 ± 13.62 years, 69.4% men) with normally functioning (BAV-nf), mild AS, moderate AS, and severe AS with preserved left ventricular ejection fraction (LVEF ≥ 52%) were included. 30 healthy volunteers were recruited as the control group. Multidirectional strain and volume analysis were performed by three-dimensional speckle tracking echocardiography(3D-STE).ResultsGlobal longitudinal strain (GLS), and global radial strain (GRS) were reduced in BAV-nf patients compared with the controls. With each categorical of AS severity from BAV-nf to severe AS, there was an associated progressive impairment of GLS and GRS (all P

Abstract Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)‐induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R‐induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation‐induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R‐induced ferroptosis. TPABTBP exhibits excellent LD‐specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super‐resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0–9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA‐approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Abstract Background Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for the targeted delivery of bone marrow mesenchymal stem cells (MSCs) to the ischemic myocardium. However, the limited migration capacity and poor survival of MSCs remains a major therapeutic barrier. The present study was performed to investigate the synergistic effect of UTMD with platelet-derived growth factor BB (PDGF-BB) on the homing of MSCs for acute myocardial infarction (AMI). Methods MSCs from male donor rats were treated with PDGF-BB, and a novel microbubble formulation was prepared using a thin-film hydration method. In vivo, MSCs with or without PDGF-BB pretreatment were transplanted by UTMD after inducing AMI in experimental rats. The therapeutic efficacy of PDGF-BB-primed MSCs on myocardial apoptosis, angiogenesis, cardiac function and scar repair was estimated. The effects and molecular mechanisms of PDGF-BB on MSC migration and survival were explored in vitro. Results The results showed that the biological effects of UTMD increased the local levels of stromal-derived factor-1 (SDF-1), which promoted the migration of transplanted MSCs to the ischemic region. Compared with UTMD alone, UTMD combined with PDGF-BB pretreatment significantly increased the cardiac homing of MSCs, which subsequently reduced myocardial apoptosis, promoted neovascularization and tissue repair, and increased cardiac function 30 days after MI. The vitro results demonstrated that PDGF-BB enhanced MSC migration and protected these cells from H2O2-induced apoptosis. Mechanistically, PDGF-BB pretreatment promoted MSC migration and inhibited H2O2-induced MSC apoptosis via activation of the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway. Furthermore, crosstalk between PDGF-BB and stromal-derived factor-1/chemokine receptor 4 (SDF-1/CXCR4) is involved in the PI3K/AKT signaling pathway. Conclusion The present study demonstrated that UTMD combined with PDGF-BB treatment could enhance the homing ability of MSCs, thus alleviating AMI in rats. Therefore, UTMD combined with PDGF-BB pretreatment may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases.

Mitral regurgitation is the second most prevalent valvular disease, with primary mitral regurgitation (PMR) accounting for 61%–67% of cases. Chronic PMR can result in progressive left ventricular remodeling and dysfunction, ultimately leading to heart failure or other adverse cardiac events. This, in turn, necessitates frequent referrals, hospitalizations, and cardiac surgeries. The optimal timing for PMR surgery has been a subject of ongoing debate and remains a controversial issue. Presently, it is recommended that patients with chronic PMR undergo earlier mitral valve surgery to enhance post-operative outcomes. For example, the recommendation of European and American guidelines about left ventricular end-systolic diameter for surgery has been altered from 45 mm to 40 mm. Echocardiographic parameters are regarded as noteworthy indicators for intervention in patients with PMR. Extensive research has been undertaken in the field of echocardiography to identify more effective indicators that can propose the optimal timing for surgery, encompassing both conventional and novel echocardiography parameters. However, some parameters are not known to clinicians and the cut-off values for these parameters have shown some variations. Furthermore, a comprehensive review of this topic is currently missing. Consequently, this review aims to provide a thorough summary and elucidation of the prognostic significance of various echocardiographic measurements and their corresponding cut-off values, to help the clinical decision-making and further improve the outcomes of patients with PMR.

Abstract Background With the development of hip arthroplasty technology and rapid rehabilitation theory, the number of hip arthroplasties in elderly individuals is gradually increasing, and their satisfaction with surgery is also gradually improving. However, for elderly individuals, many basic diseases, poor nutritional status, the probability of surgery, anaesthesia and postoperative complications cannot be ignored. How to reduce the incidence of postoperative complications, optimize medical examination for elderly patients, and reasonably allocate medical resources. This study focuses on the construction of a clinical prediction model for planned transfer to the ICU after hip arthroplasty in elderly individuals. Methods We retrospectively analysed 325 elderly patients who underwent hip arthroplasty. The general data and preoperative laboratory test results of the patients were collected. Univariate and multivariate logistic regression analyses were performed to screen independent influencing factors. The backwards LR method was used to establish the prediction model. Then, we assessed and verified the degree of discrimination, calibration and clinical usefulness of the model. Finally, the prediction model was rendered in the form of a nomogram. Results Age, blood glucose, direct bilirubin, glutamic-pyruvic transaminase, serum albumin, prothrombin time and haemoglobin were independent influencing factors of planned transfer to the ICU after hip arthroplasty. The area under the curve (AUC) of discrimination and the 500 bootstrap internal validation AUC of this prediction model was 0.793. The calibration curve fluctuated around the ideal curve and had no obvious deviation from the ideal curve. When the prediction probability was 12%-80%, the clinical decision curve was above two extreme lines. The discrimination, calibration and clinical applicability of this prediction model were good. The clinical prediction model was compared with the seven factors in the model for discrimination and clinical use. The discrimination and clinical practicability of this prediction model were superior to those of the internal factors. Conclusion The prediction model has good clinical prediction ability and clinical practicability. The model is presented in the form of a linear graph, which provides an effective reference for the individual risk assessment of patients.

Abstract Trauma theory, which emerged in the early 1990s, unveiled the deep-rooted violence characterising modern civilisation. As an essential subset of trauma studies, trauma literature acts as a testament to victims’ experiences. A narrative technique pivotal to this literature is the fragmented narrative, mirroring both the inherent nature of trauma and its external portrayal. This technique aptly captures the often-ineffable nature of traumatic experiences. This research scrutinises the application of fragmented narrative in two seminal works: Amy Tan’s The Kitchen God’s Wife published in 1991 and Toni Morrison’s Beloved published in 1987. Through a lens focused on mother-daughter dynamics and trauma representation, the study illuminates the novels’ shared themes of motherhood and the agonising internal battles of trauma-afflicted mothers. Tan and Morrison, using fragmented narrative, vividly depict their protagonists’ harrowing traumas, and offer invaluable insights into the experiences of marginalised communities. The emphasis on trauma literature is pivotal, both for a comprehensive understanding of traumatic events and the advancement of trauma research. This underscores the paramountcy of acknowledging personal and communal traumas and championing a humane approach to trauma victims.