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.

Cribiform and intraductal carcinoma in hereditary prostate cancer: clinical and pathological analysis of 20 cases.

Cribiform and intraductal carcinoma are patterns of aggressive prostate carcinoma. This study investigated the clinical and pathological features of hereditary prostate cancer. Twenty cases of hereditary prostate cancer from 11 family lines treated at the First Affiliated Hospital of Zhejiang University School of Medicine between 2016-2022 were included to summarize the clinical and pathological features by analyzing clinical information including follow up the survival of the patients and pathological features. Of the 20 hereditary prostate cancer cases, 19 were radical prostate specimens and 1 was a biopsy specimen. The mean age at diagnosis of the patients was 67.55 years and the mean PSA was 15.44 ng/ml, of which 10 cases had PSA ≥ 10 ng/ml and 5 cases had PSA ≥ 20 ng/ml. Of the 19 radical prostate specimens, Gleason cribriform pattern (Gleason grade 4) of PCa is observed in 15 cases (78.95%), and intraductal carcinoma, usually a rare form, is seen in 9 cases (47.3%). Two cases demonstrated pelvic lymph node metastasis, and 7 cases (35%) belonged to high-risk or very high-risk PCa. One case (5.26%) showed partial deletion of expression of RB1, and 13 cases (68.42%) showed deletion of expression of PTEN. Follow-up was 4-90 months, 2 cases had biochemical recurrence and 1 case died from prostate cancer. The mean age at diagnosis of this group of patients with hereditary prostate cancer was 67.55 years, the mean preoperative PSA was 15.44 ng/ml, and their histomorphology was characterized by a high percentage of intraductal carcinoma and cribriform pattern of the prostate.

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.

Shexiang Baoxin Pill enriches Lactobacillus to regulate purine metabolism in patients with stable coronary artery disease.

BACKGROUND: It has been clinically confirmed that the Shexiang Baoxin Pill (SBP) dramatically reduces the frequency of angina in patients with stable coronary artery disease (SCAD). However, potential therapeutic mechanism of SBP has not been fully explored. PURPOSE: The study explored the therapeutic mechanism of SBP in the treatment of SCAD patients. METHODS: We examined the serum metabolic profiles of patients with SCAD following SBP treatment. A rat model of acute myocardial infarction (AMI) was established, and the potential therapeutic mechanism of SBP was explored using metabolomics, transcriptomics, and 16S rRNA sequencing. RESULTS: SBP decreased inosine production and improved purine metabolic disorders in patients with SCAD and in animal models of AMI. Inosine was implicated as a potential biomarker for SBP efficacy. Furthermore, SBP inhibited the expression of genes involved in purine metabolism, which are closely associated with thrombosis, inflammation, and platelet function. The regulation of purine metabolism by SBP was associated with the enrichment of Lactobacillus. Finally, the effects of SBP on inosine production and vascular function could be transmitted through the transplantation of fecal microbiota. CONCLUSION: Our study reveals a novel mechanism by which SBP regulates purine metabolism by enriching Lactobacillus to exert cardioprotective effects in patients with SCAD. The data also provide previously undocumented evidence indicating that inosine is a potential biomarker for evaluating the efficacy of SBP in the treatment of SCAD.

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.

Unveiling gene regulatory networks during cellular state transitions without linkage across time points.

Time-stamped cross-sectional data, which lack linkage across time points, are commonly generated in single-cell transcriptional profiling. Many previous methods for inferring gene regulatory networks (GRNs) driving cell-state transitions relied on constructing single-cell temporal ordering. Introducing COSLIR (COvariance restricted Sparse LInear Regression), we presented a direct approach to reconstructing GRNs that govern cell-state transitions, utilizing only the first and second moments of samples between two consecutive time points. Simulations validated COSLIR's perfect accuracy in the oracle case and demonstrated its robust performance in real-world scenarios. When applied to single-cell RT-PCR and RNAseq datasets in developmental biology, COSLIR competed favorably with existing methods. Notably, its running time remained nearly independent of the number of cells. Therefore, COSLIR emerges as a promising addition to GRN reconstruction methods under cell-state transitions, bypassing the single-cell temporal ordering to enhance accuracy and efficiency in single-cell transcriptional profiling.

Atorvastatin combined with imipenem alleviates lung injury in sepsis by inhibiting neutrophil extracellular trap formation via the ERK/NOX2 signaling pathway.

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.

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.

Low gelatin concentration assisted cellulose nanocrystals stabilized high internal phase emulsion: The key role of interaction.

Low concentrations of gelatin (0.02-0.20 wt%) were applied to regulate the surface and interface properties of CNC (0.50 wt%) by forming CNC/G complexes. As gelatin concentration increased from 0 to 0.20 wt%, the potential value of CNC/G gradually changed from -44.50 to -17.93 mV. Additionally, various gelatin concentrations led to micromorphology changes of CNC/G complexes, with the formation of particle interconnection at gelatin concentration of 0.10 wt%, followed by network structure and enhanced aggregation at gelatin concentration of 0.15 and 0.20 wt% respectively. The water contact angle (25.91°-80.23°) and interface adsorption capacity of CNC/G were improved due to hydrophobic group exposure of gelatin. When gelatin concentration exceeded 0.10 % at a fixed oil phase volume fraction (75 %), a high internal phase emulsion (HIPE) stabilized by CNC/G can be formed with a good storage stability. The rheological and microstructure results of HIPE confirmed that low gelatin concentration can assist CNC to form stable emulsion structure. Especially, the auxiliary stabilization mechanism of various gelatin concentration was different. CNC/G-0.10 % and CNC/G-0.15 % stabilized HIPE mainly depended on the enhanced interface adsorption and network structure, while CNC/G-0.20 % stabilized HIPE mainly relied on enhanced interface adsorption/accumulation due to weak electrostatic repulsion and aggregate granular morphology of CNC/G-0.20 %.

Mitochondria protective and anti-apoptotic effects of peripheral benzodiazepine receptor and its ligands on the treatment of asthma in vitro and vivo.

BACKGROUND: Asthma is a prevalent respiratory inflammatory disease. Abnormal apoptosis of bronchial epithelial cells is one of the major factors in the progression of asthma. Peripheral benzodiazepine receptors are highly expressed in bronchial epithelial cells, which act as a component of the mitochondrial permeability transition pore to regulate its opening and closing and apoptosis of bronchial epithelial cells. We aimed to investigate the mechanisms by which peripheral benzodiazepine receptor and its ligands, agonist 4'-Chlorodiazepam (Ro5-4864) and antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11,195), modulate the mitochondrial function and cell apoptosis in the treatment of asthma. METHODS: In vitro study, Ro5-4864 and PK 11,195 were utilized to pretreat cells prior to the inflammatory injury induced by Lipopolysaccharide. The reactive oxygen species, the apoptosis of cell, the mitochondrial membrane potentials, the ultrastructures of the mitochondria and the expression levels of peripheral benzodiazepine receptors and apoptosis-related proteins and genes were detected. In vivo study, mice were administrated intraperitoneally with Ro5-4864 and PK 11,195 before sensitized and challenged by ovalbumin. Serum IgE and bronchoalveolar lavage fluid cytokines were detected, and lung tissues were underwent the histopathological examination. RESULTS: The ligands of peripheral benzodiazepine receptor counteracted the effects of the increase of reactive oxygen species, the elevated extent of apoptosis, the decrease of mitochondrial membrane potentials and the disruption of mitochondrial ultrastructures induced by Lipopolysaccharide. The ligands also promoted the expression of anti-apoptosis-related proteins and genes and inhibited the expression of pro-apoptosis-related proteins and genes. Besides, the ligands reduced the levels of serum IgE and bronchoalveolar lavage fluid cytokines in asthmatic mice and attenuated the histopathological damage of lungs. CONCLUSION: Peripheral benzodiazepine receptor serves as a potential therapeutic target for the treatment of asthma, with its ligands exerting mitochondrial protective and anti-apoptotic effects on bronchial epithelial cells.

Opportunistic sampling of yellow canary (Crithagra flaviventris) has revealed a high genetic diversity of detected parvoviral sequences.

Parvoviruses are known to be significant viral pathogens that infect a wide range of species globally. However, little is known about the parvoviruses circulating in Australian birds, including yellow canaries. Here, we present four parvoviral sequences including three novel parvoviruses detected from 10 yellow canaries (Crithagra flaviventris), named canary chaphamaparvovirus 1 and -2 (CaChPV1 and CaChPV2), canary dependoparvovirus 1 and -2 (CaDePV1 and CaDePV2). The whole genome sequences of CaChPV1, CaChPV2, CaDePV1, and CaDePV2 showed the highest identity with other parvoviruses at 76.4%, 75.9%, 84.0%, and 59.1%, respectively. Phylogenetic analysis demonstrated that CaChPV1 and CaChPV2 were clustered within the genus Chaphamaparvovirus. Meanwhile, CaDePV1 and CaDePV2 fall within the genus Dependoparvovirus and have the closest evolutionary relationship to the bird-associated dependoparvoviruses. Overall, this study enriched our understanding of the genetic diversity among avian parvoviruses within the Parvoviridae family.

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.

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.

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.

Autophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation.

Autophagy modulates the degradation and recycling of intracellular materials and contributes to male gametophyte development and male fertility in plants. However, whether autophagy participates in seed development remains largely unknown. Here, we demonstrate that autophagy is crucial for timely programmed cell death (PCD) in the integumentary tapetum, the counterpart of anther tapetum, influencing embryo pattern formation and seed viability. Inhibition of autophagy resulted in delayed PCD of the integumentary tapetum and defects in embryo patterning. Cell-type-specific restoration of autophagic activities revealed that the integumentary tapetum plays a non-autonomous role in embryo patterning. Furthermore, high-throughput, comprehensive lipidomic analyzes uncovered an unexpected seed-developmental-stage-dependent role of autophagy in seed lipid metabolism: it contributes to triacylglycerol degradation before fertilization and to triacylglycerol biosynthesis after fertilization. This study highlights the critical role of autophagy in regulating timely integumentary tapetum PCD and reveals its significance in seed lipid metabolism and viability.

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways.

Dietary protein supplementation has emerged as a promising strategy in combating sarcopenia. Furthermore, searching for alternatives of animal proteins has been a hot topic. The present study aimed to investigate the effects of zein peptides on C2C12 myoblasts and explore their potential molecular mechanisms. The proliferative, cell cycle, and anti-apoptotic activities of zein peptides were evaluated. Peptidomics analysis and transcriptome sequencing were employed to explore the structure-activity relationship and underlying molecular mechanisms. The results indicated that zein peptides (0.05-0.2 mg/mL) exerted a significant proliferation-promoting impact on C2C12 cells, via increasing cell viability by 33.37 to 42.39%. Furthermore, zein peptides significantly increased S phase proportion and decreased the apoptosis rate from 34.08% (model group) to 28.96% in C2C12 cells. In addition, zein peptides exhibited a pronounced anti-apoptotic effect on C2C12 cells. Zein peptides are abundant in branch-chain amino acids, especially leucine. Transcriptomics analysis revealed that zein peptides can promote proliferation, accelerate cell cycle, and improve protein synthesis of muscle cells through mTORC1 and mTORC2 signaling pathways.

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.

Transgenerational toxicity induced by maternal AFB1 exposure in Caenorhabditis elegans associated with underlying epigenetic regulations.

Aflatoxin B1 (AFB1), usually seriously contaminates in grain and oil foods or feed, displayed significant acute and chronic toxic effects in human and animal populations. However, little is known about the transgenerational toxic effects induced by a maternal AFB1 intake at a lower dose on offspring. In our study, only parental wild-type Caenorhabditis elegans was exposed to AFB1 (0-8 µg/ml) and the following three filial generations were grown on AFB1-free NGM. Results showed that the toxic effects of AFB1 on the growth (body length) and reproduction (brood size, generation time and morphology of gonad arm) can be transmitted through generations. Moreover, the levels of MMP and ATP were irreversibly inhibited in the filial generations. By using RNomics and molecular biology techniques, we found that steroid biosynthesis, phagosome, valine/leucine/isoleucine biosynthesis and oxidative phosphorylation (p < 0.05) were the core signaling pathways to exert the transgenerational toxic effects on nematodes. Also, notably increased histone methylation level at H3K36me3 was observed in the first generation. Taken together, our study demonstrated that AFB1 has notable transgenerational toxic effects, which were resulted from the complex regulatory network of various miRNAs, mRNAs and epigenetic modification in C. elegans.

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.