Curvature-mediated source and sink effects on the genesis of premature ventricular complexes in long QT syndrome.

Premature ventricular complexes (PVCs) are spontaneous excitations occurring in the ventricles of the heart that are associated with ventricular arrhythmias and sudden cardiac death. Under long QT conditions, PVCs can be mediated by repolarization gradient (RG) and early afterdepolarizations (EADs), yet the effects of heterogeneities or geometry of the RG or EAD regions on PVC genesis remain incompletely understood. In this study, we use computer simulation to systematically investigate the effects of the curvature of the RG border region on PVC genesis under long QT conditions. We show that PVCs can be either promoted or suppressed by negative or positive RG border curvature depending on the source and sink conditions. When the origin of oscillation is in the source region and the source is too strong, a positive RG border curvature can promote PVCs by causing the source area to oscillate. When the origin of oscillation is in the sink region, a negative RG border curvature can promote PVCs by causing the sink area to oscillate. Furthermore, EAD-mediated PVCs are also promoted by negative border curvature. We also investigate the effects of wavefront curvature and show that PVCs are promoted by convex but suppressed by concave wavefronts; however, the effect of wavefront curvature is much smaller than that of RG border curvature. In conclusion, besides the increase of RG and occurrence of EADs caused by QT prolongation, the geometry of the RG border plays important roles in PVC genesis, which can greatly increase the risk of arrhythmias in cardiac diseases.NEW & NOTEWORTHY The effects of the curvature or geometry of the repolarization gradient region and wavefront curvature on the genesis of premature ventricular complexes are systematically investigated using computer modeling and simulation. Premature ventricular complexes can be promoted by either positive or negative curvature of the gradient region depending on the source and sink conditions. The underlying mechanisms of the curvature effects are revealed, which provides mechanistic insights into arrhythmogenesis in cardiac diseases.

Optimizing Surface State Electrons of Topological Semi-Metal by Atomic Doping for Enhanced Hydrogen Evolution Reaction.

Topological materials carrying topological surface states (TSSs) have extraordinary carrier mobility and robustness, which provide a new platform for searching for efficient hydrogen evolution reaction (HER) electrocatalysts. However, the majority of these TSSs originate from the sp band of topological quantum catalysts rather than the d band. Here, based on the density functional theory calculation, it is reported a topological semimetal Pd3Sn carrying TSSs mainly derived from d orbital and proposed that optimizing surface state electrons of Pd3Sn by introduction heteroatoms (Ni) can promote hybridization between hydrogen atoms and electrons, thereby reducing the Gibbs free energy (ΔGH) of adsorbed hydrogen and improving its HER performance. Moreover, this is well verified by electrocatalytic experiment results, the Ni-doped Pd3Sn (Ni0.1Pd2.9Sn) show much lower overpotential (-29 mV vs RHE) and Tafel slope (17 mV dec-1) than Pd3Sn (-39 mV vs RHE, 25 mV dec-1) at a current density of 10 mA cm-2. Significantly, the Ni0.1Pd2.9Sn nanoparticles exhibit excellent stability for HER. The electrocatalytic activity of Ni0.1Pd2.9Sn nanoparticles is superior to that of commercial Pt. This work provides an accurate guide for manipulating surface state electrons to improve the HER performance of catalysts.

Effects of Testosterone in Mediating the Relationship Between Daytime Napping and Osteoporosis in European Populations: A Mendelian Randomization Study.

We aimed to explore the causal effect of daytime napping on the risk of osteoporosis and the mediation role of testosterone in explaining this relationship. Summary data for Mendelian randomization (MR) analysis were obtained from the IEU OpenGWAS database. Univariable MR(UVMR) analysis and multiple sensitivity analyses were applied to explore the casual relationship between daytime napping and bone mineral density (BMD)/osteoporosis. We also conducted multivariable Mendelian randomization (MVMR) analysis to evaluate the correlation between testosterone-associated single-nucleotide variations and BMD/osteoporosis. Then, mediation analysis was performed to explore whether the association between daytime napping and BMD/osteoporosis was mediated via testosterone. Genetically predicted daytime napping was significantly associated with femoral neck BMD (ß [95% CI]: 0.2573 [0.0487, 0.4660]; P = 0.0156), lumbar spine BMD (ß [95% CI]: 0.2526 [0.0211, 0.4840]; P = 0.0324), and osteoporosis (OR [95% CI]: 0.5063 [0.2578, 0.9942]; P = 0.0481). ß and 95%CIs indicate the standard deviation (SD) unit of BMD increase per category increase in daytime napping. OR and 95%CIs represent the change in the odds ratio of osteoporosis per category increase in daytime napping. We observed a potentially causal effect of more frequent daytime napping on higher BMD and a lower risk of osteoporosis. Daytime napping was causally associated with a higher level of bioavailable testosterone (ß [95% CI]: 0.1397 [0.0619, 0.2175]; P = 0.0004). ß and 95%CIs represent the change in the SD of testosterone per category increase in daytime napping. Furthermore, the causal effects of daytime napping on BMD/osteoporosis were partly mediated by bioavailable testosterone. Daytime napping can efficiently increase BMD and reduce the risk of osteoporosis, and testosterone plays a key mediating role in this process.

Intraindividual comparison of CT and MRI for predicting vessels encapsulating tumor clusters in hepatocellular carcinoma.

OBJECTIVES: To establish and validate scoring models for predicting vessels encapsulating tumor clusters (VETC) in hepatocellular carcinoma (HCC) using computed tomography (CT) and magnetic resonance imaging (MRI), and to intra-individually compare the predictive performance between the two modalities. METHODS: We retrospectively included 324 patients with surgically confirmed HCC who underwent preoperative dynamic CT and MRI with extracellular contrast agent between June 2019 and August 2020. These patients were then divided into a discovery cohort (n = 227) and a validation cohort (n = 97). Imaging features and Liver Imaging Reporting and Data System (LI-RADS) categories of VETC-positive HCCs were evaluated. Logistic regression analyses were conducted on the discovery cohort to identify clinical and imaging predictors associated with VETC-positive cases. Subsequently, separate CT-based and MRI-based scoring models were developed, and their diagnostic performance was compared using generalized estimating equations. RESULTS: On both CT and MRI, VETC-positive HCCs exhibited a higher frequency of size > 5.0 cm, necrosis or severe ischemia, non-smooth tumor margin, targetoid appearance, intratumor artery, and heterogeneous enhancement with septations or irregular ring-like structure compared to VETC-negative HCCs (all p < 0.05). Regarding LI-RADS categories, VETC-positive HCCs were more frequently categorized as LR-M than VETC-negative cases (all p < 0.05). In the validation cohort, the CT-based model showed similar sensitivity (76.7% vs. 86.7%, p = 0.375), specificity (83.6% vs. 74.6%, p = 0.180), and area under the curve value (0.80 vs. 0.81, p = 0.910) to the MRI-based model in predicting VETC-positive HCCs. CONCLUSION: Preoperative CT and MRI demonstrated comparable performance in the identification of VETC-positive HCCs, thus displaying promising predictive capabilities. CLINICAL RELEVANCE STATEMENT: Both computed tomography and magnetic resonance imaging demonstrated promise in preoperatively identifying the vessel-encapsulating tumor cluster pattern in hepatocellular carcinoma, with no statistically significant difference between the two modalities, potentially adding additional prognostic value. KEY POINTS: Computed tomography (CT) and magnetic resonance imaging (MRI) show promise in the preoperative identification of vessels encapsulating tumor clusters-positive hepatocellular carcinoma (HCC). HCC with vessels encapsulating tumor cluster patterns were more frequently LR-M compared to those without. These CT and MRI models showed comparable ability in identifying vessels encapsulating tumor clusters-positive HCC.

The novel small molecule E0924G dually regulates bone formation and bone resorption through activating the PPARδ signaling pathway to prevent bone loss in ovariectomized rats and senile mice.

Osteoporosis is particularly prevalent among postmenopausal women and the elderly. In the present study, we investigated the effect of the novel small molecule E0924G (N-(4-methoxy-pyridine-2-yl)-5-methylfuran-2-formamide) on osteoporosis. E0924G significantly increased the protein expression levels of osteoprotegerin (OPG) and runt-related transcription factor 2 (RUNX2), and thus significantly promoted osteogenesis in MC3T3-E1 cells. E0924G also significantly decreased osteoclast differentiation and inhibited bone resorption and F-actin ring formation in receptor activator of NF-κB ligand (RANKL)-induced osteoclasts from RAW264.7 macrophages. Importantly, oral administration of E0924G in both ovariectomized (OVX) rats and SAMP6 senile mice significantly increased bone mineral density and decreased bone loss compared to OVX controls or SAMR1 mice. Further mechanistic studies showed that E0924G could bind to and then activate peroxisome proliferator-activated receptor delta (PPARδ), and the pro-osteoblast effect and the inhibition of osteoclast differentiation induced by E0924G were significantly abolished when PPARδ was knocked down or inhibited. In conclusion, these data strongly suggest that E0924G has the potential to prevent OVX-induced and age-related osteoporosis by dual regulation of bone formation and bone resorption through activation of the PPARδ signaling pathway.

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

Effects of atrazine on movement, metabolism and gene expression in Pelophylax nigromaculatus larvae under global warming.

Global warming and environmental pollutants both pose a threat to the behavior and physiology of animals, but research on the combined effects of the two is limited. Atrazine, a widely used herbicide, has toxic effects on organisms. In this study, the effects of environmental concentrations of atrazine exposure (100 µg/L) for seven days on the movement, metabolism and gene expression related to motility of Pelophylax nigromaculatus larvae (GS8) were investigated under global warming. The results showed that compared to the optimal growth temperature (18 °C), atrazine treatment under global warming (21 °C) significantly increased the average speed (about 11.2 times) and maximum acceleration (about 1.98 times) of P. nigromaculatus larvae, altered the relative abundance of 539 metabolites, including Formyl-5-hydroxykynurenamine, 2,4-Dihydroxybenzophenone, and FAPy-adenine, and changed the nucleotide metabolism, pyrimidine metabolism, glycerophospholipid metabolism, and purine metabolism, as well as increased the gene expression of SPLA2 (about 6.46 times) and CHK (about 3.25 times). In summary, atrazine treatment under global warming caused metabolic disorders in amphibian larvae and increased the expression of some movement-related genes in the brain, resulting in abnormally active.

Design, bioactivity and mechanism of N'-phenyl pyridylcarbohydrazides with broad-spectrum antifungal activity.

Succinate dehydrogenase inhibitors (SDHIs) as one of the fastest-growing fungicide categories for plant protection. In this study, a series of N'-phenyl pyridylcarbohydrazides as analogues of commercial SDHIs were designed and evaluated for inhibition activity on phytopathogenic fungi to search for potential novel SDHIs. The determination of antifungal activity in vitro and in vivo led to the discovery of a series of compounds with high activity and broad-spectrum property. Especially, N'-(4-fluorophenyl)picolinohydrazide (1c) and N'-(3,4-fluorophenyl)picolinohydrazide (1ae) showed 0.041-1.851 µg/mL of EC50 values on twelve fungi, superior to positive controls carbendazim and boscalid. In vivo activity, 1c at 50 µg/mL showed 61% of control efficacy at the post-treatment 9th day for the infection of P. piricola on apples, slightly smaller than 70% of carbendazim. In terms of action mechanism, 1c showed strong inhibition activity with IC50 of 0.107 µg/mL on SDH in Alternaria brassicae, superior to positive SDHI boscalid (IC50 0.182 µg/mL). Molecular docking indicated that 1c can well bind with the ubiquinone-binding region of SDH mainly by hydrogen bond, carbon hydrogen bond, π-alkyl, amide-π stacking, F-N and F-H interactions. Furthermore, scanning and transmission electron micrographs showed that 1c was able to obviously change the structure of mycelia and cell membrane. Fluorescence staining analysis showed that 1c could increase both the intracellular reactive oxygen species level and mitochondrial membrane potential. Finally, seed germination test, seedling growth test and cytotoxicity assay showed that 1c had very low toxicity to plant growth and mammalian cells. Thus, N'-phenyl pyridylcarbohydrazides especially 1c and 1ae can be considered promising fungicide alternatives for plant protection.

Association between composite dietary antioxidant index and epilepsy in American population: a cross-sectional study from NHANES.

BACKGROUND: Epilepsy is a major global health challenge, affecting approximately 50 million people across the globe and resulting in significant economic impacts on individuals and society. Oxidative stress is implicated in the pathogenesis of epilepsy, highlighting the potential of antioxidant-rich dietary patterns in offering preventive and protective benefits by mitigating oxidative stress. The Composite Dietary Antioxidant Index (CDAI) provides a measure for assessing dietary antioxidant intake, yet its link to epilepsy remains unexplored. METHODS: Our analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2013 to 2018, including 20,180 screened participants. Weighted logistic regression models were employed to examine the association between the CDAI and epilepsy prevalence. Non-linear associations were explored through restricted cubic splines (RCS), and the relationships between individual antioxidant components within the CDAI and epilepsy were also assessed. RESULTS: After adjusting for potential confounders, a negative association between the CDAI and epilepsy was suggested (OR = 0.991; p = 0.087, 95% CI [0.819,1.014]). Stratification of CDAI into quartiles revealed a significantly reduced risk of epilepsy in higher CDAI quartiles (Q3 and Q4) compared to the lowest quartile (Q1) (Q3: OR = 0.419; p = 0.030, 95% CI [0.192, 0.914]; Q4: OR = 0.421; p = 0.004, 95% CI [0.239, 0.742]), with a significant trend observed across quartiles (p for trend = 0.013). RCS analysis suggested a nonlinear association between CDAI levels and epilepsy (non-linear p = 0.049), which, however, was not statistically significant after full adjustment (non-linear p = 0.103). Additionally, significant negative correlations with epilepsy were observed for vitamin A and zinc (Vitamin A: OR = 0.999; p = 0.012, 95% CI [0.998, 1.000]; Zinc: OR = 0.931; p = 0.042, 95% CI [0.869, 0.997]). CONCLUSIONS: Our research indicates a correlation where higher CDAI levels correspond to a reduced risk of epilepsy. Therefore, embracing a diet rich in antioxidants could be beneficial in preventing epilepsy. This finding holds considerable potential for shaping future strategies in both epilepsy prevention and treatment.

Chinese Medicine's Effects Against Advanced Gastric Cancer: A Single-center, Randomized, Double-blind, Controlled Clinical Trial.

Context: At present, medical practitioners commonly use surgery and perioperative chemotherapy, radiotherapy, and biological targeted therapy in clinical treatment of gastric cancer. Western medicine treatment can quickly treat patients' lesions but may cause adverse reactions. TCM can prevent the occurrence of toxic side effects and alleviate the side effects of Western medicine. Objectives: The study intended to explore the clinical efficacy of traditional Chinese medicine (TCM) combined with Western medicine in the treatment of advanced gastric cancer. Design: The research team performed a randomized, double-blind, controlled clinical trial. Setting: The study took place at the Cangzhou Central Hospital in Hebei, China. Participants: Participants were 102 patients with advanced gastric cancer who had been admitted to the hospital between February 2021 and March 2023. Interventions: The research team randomly divided participants into two groups, with 51 participants in each group: (1) the TCM group, who received TCM only, and (2) the combination group, who received chemotherapy combined with TCM. Outcome Measures: The research team measured: (1) clinical efficacy; (2) TCM syndrome efficacy; (3) levels of the blood tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen Sialyl-Lewis a (CA199), and carbohydrate antigen 72-4 (CA72-4); (4) psychological status using the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS); and (5) incidence of adverse reactions. Results: At baseline, no significant differences existed between the two groups in the clinical indicators. Postintervention compared to the TCM group, the combination group had significantly: (1) higher clinical efficacy (P = .003), (2) higher TCM syndrome efficacy (P = .003), (3) higher level of CEA and lower levels of CA199, and CA72-4 (all P = .000); (4) lower SAS scores and SDS scores (both P = .000); and (5) lower incidence of adverse reactions (P = .007). Conclusions: TCM, in the treatment of patients with advanced gastric cancer, can achieve good therapeutic effects. Combined with chemotherapy, patients' clinical efficacy can improve, level of blood tumor markers can decrease, psychological state can improve, and incidence of adverse reactions can decrease. Its clinical use had significant effects, and physicians can promote and use them.

Clinical Study of 32 Patients with Advanced Pancreatic Cancer Treated with Traditional Chinese Medicine Combined with Chemotherapy.

Objective: Our aim was to investigate the effect of the clinical application of Traditional Chinese Medicine (TCM) combined with chemotherapy in the treatment of advanced pancreatic cancer. Methods: The study participants were divided into 2 groups: the combined treatment group, comprised of 32 patients with advanced pancreatic cancer admitted to Zhejiang Provincial People's Hospital in China between June 2021 and June 2022 who received TCM combined with chemotherapy; and the control group: 32 patients with advanced pancreatic cancer admitted to Zhejiang Provincial People's Hospital in China between June 2021 and June 2022 who received chemotherapy alone. The TCM symptom score, TCM clinical efficacy, Western medicine clinical efficacy, patient quality of life (QoL) and incidence of adverse events (AEs) were compared in the 2 groups. Results: Prior to treatment, there was no significant difference in the patients' general clinical condition in the 2 groups (P > .05); after treatment, the TCM symptom score in the combined treatment group (16.62±2.77) was better than in the control group (21.44±2.53), with a P < .05. The TCM and Western medicine clinical efficacy was better than in the control group, with a P < .05; QoL score was higher than in the control group, P < .05; the incidence of AEs (3.12%) was lower than in the control group (28.12%); P < .05. Conclusion: In the treatment of patients with advanced pancreatic cancer, the application of TCM combined with chemotherapy can achieve good therapeutic results, improve the patients' prognosis, effectively reduce the occurrence of AEs and continuously restore patients' QoL.

Synergistic toxicity induced by the co-exposure of tenuazonic acid and patulin in Caenorhabditis elegans: Daf-16 plays an important regulatory role.

Tenuazonic acid (TeA) and patulin (PAT), as the naturally occurring mycotoxins with various toxic effects, are often detected in environment and food chain, has attracted more and more attention due to their widespread and high contaminations as well as the coexistence, which leads to potential human and animals' risks. However, their combined toxicity has not been reported yet. In our study, C. elegans was used to evaluate the type of combined toxicity caused by TeA+PAT and its related mechanisms. The results showed that TeA and PAT can induce synergistic toxic effects based on Combination Index (CI) evaluation model (Chou-Talalay method), that is, the body length, brood size as well as the levels of ROS, CAT and ATP were significantly affected in TeA+PAT-treated group compared with those in TeA- or PAT-treated group. Besides, the expressions of oxidative (daf-2, daf-16, cyp-35a2, ctl-1, ctl-3, pmk-1, jnk-1, skn-1) and intestinal (fat-5, pod-2, egl-8, pkc-3, ajm-1, nhx-2) stress-related genes were disrupted, among which daf-16 displayed the most significant alternation. Further study on daf-16 gene defective C. elegans showed that the damages to the mutant nematodes were significantly attenuated. Since daf-2, daf-16, jnk-1 and pmk-1 are evolutionarily conserved, our findings could hint synergistic toxic effects of TeA+PAT on higher organisms.

Differentiating the impact of fine and coarse particulate matter on cause-specific cerebrovascular mortality: An individual-level, case-crossover study.

BACKGROUND AND OBJECTIVES: Many studies suggested that short-term exposure to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM2.5 and PM2.5-10 on various types of cerebrovascular disease. METHODS: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season. RESULTS: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10 µg/m3 rise in PM2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10 µg/m3 rise in PM2.5-10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season. CONCLUSIONS: Short-term exposures to both PM2.5 and PM2.5-10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae.

Influence of Spider Silk Protein Structure on Mechanical and Biological Properties for Energetic Material Detection.

Spider silk protein, renowned for its excellent mechanical properties, biodegradability, chemical stability, and low immune and inflammatory response activation, consists of a core domain with a repeat sequence and non-repeating sequences at the N-terminal and C-terminal. In this review, we focus on the relationship between the silk structure and its mechanical properties, exploring the potential applications of spider silk materials in the detection of energetic materials.

Analysis of flavor substances in Shaoxing traditional hand-made Jiafan wine with different amounts of ZaoShao liquor.

BACKGROUND: Adding ZaoShao liquor (high-concentration liquor) is one of the most important steps in the brewing process of Shaoxing Jiafan wine, a product protected by Chinese geographical indications. The focus of this study is the effect of different additive amounts of liquor on the flavor of end products. RESULTS: In this study, four kinds of Shaoxing Jiafan wine were brewed by changing the amount of ZaoShao liquor. Headspace solid-phase microextraction and gas chromatography-mass spectrometry were used to detect the flavor substances of four kinds of Jiafan wine. The difference in flavor of four kinds of Jiafan wine was evaluated by electronic nose analysis technology and verified by sensory evaluation. Finally, the reliability of the experimental results was verified through an aroma reconstruction experiment of rice wine. In this study, the differences in flavoring substances under different amounts of ZaoShao liquor were verified from various angles. The results showed that the flavors of the four kinds of wines were significantly different. CONCLUSION: The composition of flavor substances in Shaoxing rice wine varies with the amount of ZaoShao liquor. This study provided a scientific basis for the improvement of production technology of Shaoxing wine. © 2024 Society of Chemical Industry.

No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation, confounders and have reported conflicting results. Our study aimed to investigate the causal associations of periodontitis with brain atrophy and cognitive impairment through a comprehensive bidirectional Mendelian randomization (MR) research. METHODS: We incorporated two distinct genome-wide association study (GWAS) summary datasets as an exploration cohort and a replication cohort for periodontitis. Four and eight metrics were selected for the insightful evaluation of brain atrophy and cognitive impairment, respectively. The former involved cortical thickness and surface area, left and right hippocampal volumes, with the latter covering assessments of cognitive performance, fluid intelligence scores, prospective memory, and reaction time for mild cognitive impairment to Alzheimer's disease (AD), Lewy body dementia, vascular dementia and frontotemporal dementia for severe situations. Furthermore, supplementary analyses were conducted to examine the associations between the longitudinal rates of change in brain atrophy and cognitive function metrics with periodontitis. The main analysis utilized the inverse variance weighting (IVW) method and evaluated the robustness of the results through a series of sensitivity analyses. For multiple tests, associations with p-values < 0.0021 were considered statistically significant, while p-values ≥ 0.0021 and < 0.05 were regarded as suggestive of significance. RESULTS: In the exploration cohort, forward and reverse MR results revealed no causal associations between periodontitis and brain atrophy or cognitive impairment, and only a potential causal association was found between AD and periodontitis (IVW: OR = 0.917, 95% CI from 0.845 to 0.995, P = 0.038). Results from the replication cohort similarly corroborated the absence of a causal relationship. In the supplementary analyses, the longitudinal rates of change in brain atrophy and cognitive function were also not found to have causal relationships with periodontitis. CONCLUSIONS: The MR analyses indicated a lack of substantial evidence for a causal connection between periodontitis and both brain atrophy and cognitive impairment.

Adenoid cystic carcinoma of the retromolar pad region: A case report.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland malignancies, mostly occurs in the major and minor salivary glands in the oral and maxillofacial region. The development of ACC in the retromolar pad is extremely rare, which limits establishing proper diagnosis and management. PRESENTATION OF CASE: A patient described a 2-month history of finding a mass behind the lower left posterior teeth. Based on the physical examination and radiographic findings, we got an initial impression of a benign mucocele, the nature of which was to be investigated further. Pathological examination of the resected tissue resulted in a diagnosis of ACC. Follow-up visits showed no recurrence during the subsequent 54 months. DISCUSSION: In cases with an uncertain diagnosis based on medical history, clinical features and imaging examinations, it is important to proceed carefully with the possibility of a tumor in mind. CONCLUSION: ACC in the retromolar pad is rare and can be easily misdiagnosed. Clinical, radiographic, and pathological evidence confirm a definitive diagnosis. Long-term follow-up is important for the full analysis of ACC treatment.

The influence of grazing intensity on soil organic carbon storage in grassland of China: A meta-analysis.

Grazing can potentially affect grassland soil carbon storage through selective feeding, trampling and fecal excretion of livestock. The numerous case studies and a few meta-analyses have focused on grazing-induced changes in soil organic carbon (SOC) storage, but the effects of grazing on SOC in major grassland types of China are not clear. In this study, we performed a comprehensive meta-analysis to identify the impact of grazing on soil carbon in China. We found that the key factors affecting the SOC content of grazing grasslands is grazing intensity. Heavy grazing (HG) significantly decreased the SOC content by 7.5 % in major grassland types of China (95 % confidence interval (CI), -11.43 % to -3.57 %, P < 0.001). The SOC content in temperate desert steppes (7.22 %), temperate meadow-steppes (10.89 %) under heavy grazing (HG) showed significantly (P < 0.05) decreased. HG resulted in significant (P < 0.01) decreases in SOC content (6.91 %) of Kastanoze. Our study highlighted that formulating rational grazing strategies according to grassland and soil types was the key to increasing SOC storage and sequestration under climate change and increased human pressure.

Ultrasensitive fluorescence microRNA biosensor by coupling hybridization-initiated exonuclease I protection and tyramine signal amplification.

Tyramine signal amplification (TSA) has made its mark in immunoassay due to its excellent signal amplification ability and short reaction time, but its application in nucleic acid detection is still very limited. Herein, an ultrasensitive microRNA (miRNA) biosensor by coupling hybridization-initiated exonuclease I (Exo I) protection and TSA strategy was established. Target miRNA is complementarily hybridized to the biotin-modified DNA probe to form a double strand, which protects the DNA probe from Exo I hydrolysis. Subsequently, horseradish peroxidase (HRP) is attached to the duplex via the biotin-streptavidin reaction and catalyzes the deposition of large amounts of biotin-tyramine in the presence of hydrogen peroxide (H2O2), followed by the conjugation of signal molecule streptavidin-phycoerythrin (SA-PE), which generates an intense fluorescence signal upon laser excitation. This method gave broad linearity in the range of 0.1 fM - 10 pM, yielding a detection limit as low as 74 aM. An increase in sensitivity of 4 orders of magnitude was observed compared to the miRNA detection without TSA amplification. This biosensor was successfully applied to the determination of miR-21 in breast cancer cells and human serum. By further design of specific DNA probes and coupling with the Luminex xMAP technology, it could be easily extended to multiplex miRNA assay, which possesses great application potential in clinical diagnosis.

New Insights into Antioxidant Peptides: An Overview of Efficient Screening, Evaluation Models, Molecular Mechanisms, and Applications.

Antioxidant peptides are currently a hotspot in food science, pharmaceuticals, and cosmetics. In different fields, the screening, activity evaluation, mechanisms, and applications of antioxidant peptides are the pivotal areas of research. Among these topics, the efficient screening of antioxidant peptides stands at the forefront of cutting-edge research. To this end, efficient screening with novel technologies has significantly accelerated the research process, gradually replacing the traditional approach. After the novel antioxidant peptides are screened and identified, a time-consuming activity evaluation is another indispensable procedure, especially in in vivo models. Cellular and rodent models have been widely used for activity evaluation, whilst non-rodent models provide an efficient solution, even with the potential for high-throughput screening. Meanwhile, further research of molecular mechanisms can elucidate the essence underlying the activity, which is related to several signaling pathways, including Keap1-Nrf2/ARE, mitochondria-dependent apoptosis, TGF-ß/SMAD, AMPK/SIRT1/PGC-1α, PI3K/Akt/mTOR, and NF-κB. Last but not least, antioxidant peptides have broad applications in food manufacture, therapy, and the cosmetics industry, which requires a systematic review. This review introduces novel technologies for the efficient screening of antioxidant peptides, categorized with a new vision. A wide range of activity evaluation assays, encompassing cellular models, as well as rodent and non-rodent models, are provided in a comprehensive manner. In addition, recent advances in molecular mechanisms are analyzed with specific cases. Finally, the applications of antioxidant peptides in food production, therapy, and cosmetics are systematically reviewed.