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The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination.

Background The assessment of chronic disease management capabilities in healthcare institutions is an important element of chronic disease management, but the researchers did not pay attention to the impact of sample heterogeneity on the scientific validity of survey results when using relevant scales, which requires our attention. Objective To explore the impact of the heterogeneity of sample composition on the evaluation results of the scale and put forward countermeasures based on the investigation of chronic disease management quality in primary medical institutions in Chengdu. Methods In February 2022, a total of 889 medical workers was selected from 46 primary care institutions in 23 prefectures and districts (counties) of Chengdu City by using multi-stage stratified cluster sampling method. The Chinese version of Assessment of Chronic Illness Care (ACIC) was used to assess the quality scores of chronic disease management in the medical institutions. Multiple correspondence analysis was used to explore the impact of sample heterogeneity caused by different genders, years of experience, professional titles, educational levels and job composition on the scale scores. Results The total score of chronic disease management competence of medical workers was negatively correlated with their education level and positively correlated with their professional title (P

ABSTRACTBackground Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials.Research design and methods Study-1 involved subjects were randomized (1:1:1) to receive 20 μg ReCOV, 40 μg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 μg ReCOV (pilot batch, ReCOV HA), 20 μg ReCOV (commercial batch, ReCOV TC), or 30 μg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster.Results Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence.Conclusions Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV’s potential for enhanced protection, supported by strong cross-neutralization and immune persistence.Clinical Trial Registration Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium spp. that mainly contaminates wheat, corn, and other food crops, and has posed serious threats to food safety. Currently, enzymatic detoxification of DON shows promising application prospects. This paper provided an overview of the latest domestic and international research on the types of biotransformation enzymes, degradation mechanisms, structural features, detoxification enzyme mining strategies, and molecular modifications of DON. Additionally, the paper explored research trends in molecular design of mycotoxin detoxification enzymes assisted by artificial intelligence, which aimed to provide a reference for the development of bio-detoxification technology of DON in food and feed.

Research on the etiology and treatment of diabetes has made substantial progress. As a result, several new classes of anti-diabetic drugs have been introduced in clinical practice. Nonetheless, the number of patients achieving glycemic control targets has not increased for the past 20 years. Two areas of unmet medical need are the restoration of insulin sensitivity and the reversal of pancreatic beta cell failure. In this review, we integrate research advances in transcriptional regulation of insulin action and pathophysiology of beta cell dedifferentiation with their potential impact on prospects of a durable cure for patients suffering from type 2 diabetes.

As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes.

Corn steep liquer, a byproduct of corn starch production, is highly productive and nutritious, containing a large quantity of amino acids, B vitamins and growth-promoting factors, which plays an important role in fermentation engineering, feed additives and pharmaceuticals. Due to sulfite residue, mycotoxin contamination and other issues, its application in various fields is seriously limited, resulting in resource waste, environmental pollution and economic loss. This paper reviews the techniques for removing antinutritional factors, phytic acid, and sulfites in corn syrup and the pollution, prevention of fungal toxins as well as the most recent application of it in single-cell protein, amino acid fermentation and biofertilizer, aiming to provide ideas for the comprehensive utilization of corn steep liquer and maximize its economic benefits.

The purpose of this study was to obtain microbial strains capable of high-efficiency degradation of T-2 toxin and to investigate their mechanism of action. T-2 toxin-degrading microorganisms were isolated from wheat and identified and their degradation characteristics were explored; their metabolites and mechanism of action were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The results showed that two efficient T-2 toxin degrading strains, AFJ-2 and AFJ-3, were screened from 50 wheat samples and identified respectively as Curtobacterium sp. and Bacillus sp. by morphological observation and 16S rDNA sequence analysis. T-2 toxin at 5 μg/mL was completely degraded within 7 and 12 h by strains AFJ-2 and AFJ-3, respectively, and intracellular enzymes from them could significantly degrade T-2 toxin (P < 0.05) without adsorption. Strain AFJ-2 was able to convert T-2 toxin to HT-2 toxin and T-2 triol, while strain AFJ-3 could degrade T-2 toxin to produce neosolaniol (NEO). Based on the predicted degradation sites, it was hypothesized that the two strains could work together to degrade T-2 toxin to produce a new product, 4-deacetyl-NEO. The research results enrich the strain resource bank for the biodegradation of T-2 toxin, and provide a reference for the separation and purification of T-2 toxin-degrading enzymes and the excavation of functional genes.

Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.