Deubiquitinase Mysm1 regulates neural stem cell proliferation and differentiation by controlling Id4 expression.

Neural stem cells (NSCs) are critical for brain development and maintenance of neurogenesis. However, the molecular mechanisms that regulate NSC proliferation and differentiation remain unclear. Mysm1 is a deubiquitinase and is essential for the self-renewal and differentiation of several stem cells. It is unknown whether Mysm1 plays an important role in NSCs. Here, we found that Mysm1 was expressed in NSCs and its expression was increased with age in mice. Mice with Mysm1 knockdown by crossing Mysm1 floxed mice with Nestin-Cre mice exhibited abnormal brain development with microcephaly. Mysm1 deletion promoted NSC proliferation and apoptosis, resulting in depletion of the stem cell pool. In addition, Mysm1-deficient NSCs skewed toward neurogenesis instead of astrogliogenesis. Mechanistic investigations with RNA sequencing and genome-wide CUT&Tag analysis revealed that Mysm1 epigenetically regulated Id4 transcription by regulating histone modification at the promoter region. After rescuing the expression of Id4, the hyperproliferation and imbalance differentiation of Mysm1-deficient NSCs was reversed. Additionally, knockdown Mysm1 in aged mice could promote NSC proliferation. Collectively, the present study identified a new factor Mysm1 which is essential for NSC homeostasis and Mysm1-Id4 axis may be an ideal target for proper NSC proliferation and differentiation.

AtFH5-labeled secretory vesicles-dependent calcium oscillation drives exocytosis and stepwise bulge during pollen germination.

Pollen germination is an essential step for delivering sperm cells to the embryo sac for double fertilization in flowering plants. The cytosolic Ca2+ concentration ([Ca2+]cyt) and vesicle dynamics are critical for pollen germination, but their potential correlation in pollen grains is not fully understood. Here, we report that [Ca2+]cyt oscillates periodically at the prospective germination sites during pollen germination. The [Ca2+]cyt is mainly from extracellular Ca2+ ([Ca2+]ext) influx, which implicates the Ca2+-permeable ion channel cyclic nucleotide-gated channel 18 (CNGC18). The [Ca2+]cyt oscillations spatiotemporally correlate with the accumulation of secretory vesicles labeled by a formin protein AtFH5, and disruption of vesicle accumulation inhibits the [Ca2+]cyt oscillations. In turn, the [Ca2+]cyt oscillations promote exocytosis, which leads to stepwise cell extension during pollen germination. Together, these data provide a timeline of vesicle dynamics, calcium oscillation, and exocytosis during pollen germination and highlight the importance of the correlation of these events for pollen germination.

Oxymatrine suppresses colorectal cancer progression by inhibiting NLRP3 inflammasome activation through mitophagy induction in vitro and in vivo.

Chinese herb Radix sophorae tonkinensis extract oxymatrine shows anticancer effects. This study evaluated the role of oxymatrine in colorectal cancer (CRC) and the underlying molecular events in vitro and in vivo. CRC cells were treated with different doses of oxymatrine to assess cell viability, reactive oxygen species production, gene expression, and gene alterations. Meanwhile, mouse xenograft and liver metastasis models were used to assess the effects of oxymatrine using histology examination, transmission electron microscopy, and Western blot, respectively. Our results showed that oxymatrine treatment triggered CRC cell mitophagy to inhibit CRC cell growth, migration, invasion, and metastasis in vitro and in vivo. At the gene level, oxymatrine inhibited LRPPRC to promote Parkin translocation into the mitochondria and reduce the mitophagy-activated NLRP3 inflammasome. Thus, oxymatrine had an anticancer activity through LRPPRC inhibition, mitophagy induction, and NLRP3 inflammasome suppression in the CRC cell xenograft and liver metastasis models. In conclusion, the study demonstrates the oxymatrine anti- CRC activity through its unique role in regulating CRC cell mitophagy and NLRP3 inflammasome levels in vitro and in vivo.

Effects of late evening snacks on glucose homeostasis in cirrhotic patients: A meta-analysis.

BACKGROUND: Insulin resistance and hepatogenic diabetes are common complications in patients with liver cirrhosis. Previous studies have shown that reducing the fasting phase by supplying a late evening snack (LES) is a potential intervention to improve substrate utilization and liver function. However, the underlying mechanisms need to be further elucidated. The purpose of current meta-analysis is to evaluate effects of LES on glucose homeostasis in cirrhotic patients. METHODS: Electronic databases including PubMed, Web of Science, and major scientific conference sessions were searched without language restriction and carried out on March 1, 2022 with an additional manual search of bibliographies of relevant articles. A total of 4145 studies were identified, and 10 studies were eligible for the meta-analysis, comprising 631 patients (319 in the LES group and 312 in the non-LES group). Subgroup analyses were performed to investigate the effect of LES on cirrhotic patients with or without diabetes. RESULTS: Analysis showed that LES intervention had significant effects in cirrhotic patients for glycemic parameters on fasting plasma glucose, fasting insulin, and glycosylated hemoglobin respective effect sizes of -8.7, -0.86, and -0.76. Subgroup result revealed that the effect of LES on fasting plasma glucose is higher in cirrhotic patients with diabetes group than cirrhotic patients without diabetes group, and long-term LES supplementation (>2 months) was more beneficial to maintain glucose homeostasis in cirrhotic patients than that of short-term supplementation (<2 months). LES also had significant effect on nutritional metabolic parameters like including albumin and non-protein respiratory quotient. CONCLUSION: Meta-analysis indicated that LES not only improved malnutrition in cirrhotic patients with or without diabetes but also maintain glucose homeostasis in cirrhotic patients with diabetes. LES is a promising and simple intervention that beneficial to maintain glucose homeostasis in cirrhotic patients.

Actin: Static and Dynamic Studies.

The actin cytoskeleton is a highly dynamic network in plant cells, which is precisely regulated by numerous actin-binding proteins. Hence, characterizing the biochemical activities of actin-binding proteins is of great importance. Here we describe methods for determining the binding and bundling of microfilaments as well as methods for visualizing microfilaments using fluorescent phalloidin and single-molecule TIRF imaging.

Cavernous hemangioma of the ileum in a young man: A case report and review of literature.

BACKGROUND: Small intestinal cavernous hemangioma is a rare disease, especially in the ileum. It is difficult to accurately diagnose due to its hidden location and nonspecific clinical symptoms. Here, we reported a case of ileal cavernous hemangioma with chronic hemorrhage in a 20-year-old man and review the literature to gain a better understanding of this disease. CASE SUMMARY: The patient complained of intermittent melena and hematochezia for > 3 mo. The lowest hemoglobin level revealed by laboratory testing was 3.4 g/dL (normal range: 12-16 g/dL). However, the gastroscopy, colonoscopy and peroral double-balloon enteroscopy (DBE) showed no signs of bleeding. The transanal DBE detected a lesion at about 340 cm proximal to the ileocecal valve. Thus, we performed an exploratory laparoscopy and the lesion was resected. After the operation, the patient had no melena. Finally, the pathological examination identified the neoplasm as an ileal cavernous hemangioma, thereby resulting in gastrointestinal hemorrhage. CONCLUSION: This report might improve the diagnosis and treatment of ileal cavernous hemangioma.

Clonorchiasis in Patients with Biliary and Pancreatic Diseases: Diagnosis and Risk Factors.

BACKGROUND: Many epidemiological studies have investigated the risk factors for clonorchiasis, but endoscopic findings of this disease in endoscopic retrograde cholangiopancreatography (ERCP) have not been well characterized. In this study, we evaluated clonorchiasis in ERCP in patients with biliary and pancreatic diseases. METHODS: This was a retrospective two-center study in hospitalized patients who received ERCP between January 2012 and October 2018. All patients were divided into clonorchiasis and nonclonorchiasis groups. Data were analyzed using univariate analysis and multivariate analyses. RESULTS: A total of 1119 patients were included, and clonorchiasis was diagnosed in 19.2% patients. Detection of Clonorchis sinensis eggs in bile samples was higher than that in fecal samples (85.9% vs. 58.7%; P = 0.001). In multivariate analysis, male patients (95% confidence interval (CI): 1.945-4.249, P = 0.001). In multivariate analysis, male patients (95% confidence interval (CI): 1.945-4.249, P = 0.001). In multivariate analysis, male patients (95% confidence interval (CI): 1.945-4.249, P = 0.001). In multivariate analysis, male patients (95% confidence interval (CI): 1.945-4.249, P = 0.001). In multivariate analysis, male patients (95% confidence interval (CI): 1.945-4.249, P = 0.001). In multivariate analysis, male patients (95% confidence interval (CI): 1.945-4.249. CONCLUSIONS: The detection of C. sinensis eggs was significantly higher in bile than in fecal samples; thus, bile samples represent a preferable sample for the diagnosis of clonorchiasis in patients with biliary obstruction. We found that male, age ≤ 60 years old, and CBD diameter < 12 mm were independent risk factors for clonorchiasis, while papilla fistula was a protective factor.C. sinensis eggs was significantly higher in bile than in fecal samples; thus, bile samples represent a preferable sample for the diagnosis of clonorchiasis in patients with biliary obstruction. We found that male, age ≤ 60 years old, and CBD diameter < 12 mm were independent risk factors for clonorchiasis, while papilla fistula was a protective factor.

Secretory Vesicles Targeted to Plasma Membrane During Pollen Germination and Tube Growth.

Pollen germination and pollen tube growth are important biological events in the sexual reproduction of higher plants, during which a large number of vesicle trafficking and membrane fusion events occur. When secretory vesicles are transported via the F-actin network in proximity to the apex of the pollen tube, the secretory vesicles are tethered and fused to the plasma membrane by tethering factors and SNARE proteins, respectively. The coupling and uncoupling between the vesicle membrane and plasma membrane are also regulated by dynamic cytoskeleton, proteins, and signaling molecules, including small G proteins, calcium, and PIP2. In this review, we focus on the current knowledge regarding secretory vesicle delivery, tethering, and fusion during pollen germination and tube growth and summarize the progress in research on how regulators and signaling molecules participate in the above processes.

Microbial Profiles and Risk Factors of Preexisting Biliary Infection in Patients with Therapeutic Endoscopy.

BACKGROUND: The bile infection may already exist before the administration of an interventional procedure, despite no clinical manifestations of cholangitis detected. Blood cultures remained negative even in more than half of the febrile cases with cholangitis. Risk factors associated with bacterial growth in bile before the intervention are not well defined. To establish the bacterial profiles isolated from the bile samples and to identify risk factors for bacterial colonization in the bile system. METHODS: Individuals who underwent endoscopic retrograde cholangiopancreatography (ERCP) interventions were enrolled. Bile samples were aspirated and were immediately transferred into a sterile tube for storage. RESULTS: Positive bile cultures were detected in 363 (38.0%) of 956 patients, including 322 benign diseases and 41 malignances. Of 363 positive cases, 351 (96.7%) were monoinfection and 12 (3.3%) multi-infection. Escherichia coli were the most common Gram-negative bacteria (210, 56.0%), followed by Klebsiella pneumoniae (45, 12.0%). Enterococcus faecalis represented the most common Gram-positive microorganism (19, 5.07%), while Candida albicans (11, 2.93%) were the dominant fungi. Klebsiella pneumoniae were more frequently detected in malignant diseases (P = 0.046). Age, previous ERCP history or OLT history, and CBD diameter were independent risk factors for positive cultures (P < 0.05) while preoperative jaundice drug therapy was the protective factor for bile infection (P < 0.05). CONCLUSION: Monomicrobial infection was dominant among all infections, and Klebsiella pneumoniae strains were more frequently isolated from patients with malignant diseases. To effectively manage patients who are at a high risk for bile infection, a detailed diagnosis and treatment plan for each case should be prepared.