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Background Human papillomavirus (HPV) infection is an important factor leading to cervical cell abnormalities. 90% of cervical cancers are closely associated with persistent infection of high-risk HPV, with the highest correlation with HPV16 and 18. Currently available vaccines and antivirals have limited effectiveness and coverage. Guanylate binding protein 1 (GBP1) was induced by interferon gamma and involved in many important cellular processes such as clearance of various microbial pathogens. However, whether GBP1 can inhibit human papillomavirus infection is unclear. Results In this study, we found that GBP1 can effectively degrade HPV18 E6, possibly through its GTPase activity or other pathways, and E6 protein degrades GBP1 through the ubiquitin-proteasome pathway to achieve immune escape. Conclusion Therefore, GBP1 is an effector of IFN-γ anti-HPV activity. Our findings provided new insights into the treatment of HPV 18 infections.

Introduction: Bear bile powder (BBP) is widely used in the clinic and has a hypoglycemic effect, but its mechanism is not clear. Methods: In this study, type 2 diabetes mellitus (T2DM) rats induced by a high-sugar and high-fat diet combined with streptozotocin were given BBP, and biochemical indexes, pathological sections, metabonomics, intestinal microbiota (IM) and short-chain fatty acids (SCFAs) were determined. Results: The results showed that BBP could reduce blood glucose, relieve inflammation, insulin resistance, and lipid metabolism disorder, and alleviate tissue damage of the liver, spleen, kidney, and pancreas in T2DM rats. It is worth noting that BBP can reverse the changes in blood and urine metabolites in T2DM rats, which are mainly related to tryptophan metabolism, pentose and glucuronate interconversions, starch and sucrose metabolism, and glycerophospholipid metabolism. In addition, BBP restored IM disorder in T2DM rats, decreased the abundance of Allobaculum , Blautia , Dubosiella , and Anaerostipes , enriched the abundance of Lactobacillus , Romboutsia , UCG-005 , and norank_f__Eggerthellaceae , and increased the concentration of SCFAs in intestinal contents. Discussion: These findings suggest that BBP may improve T2DM by regulating multiple metabolic pathways, IM composition, and SCFAs levels.

ABSTRACT Deciphering the genetic control of grape berry traits is crucial for optimizing yield, fruit quality, and consumer acceptability. In this study, an association panel of 179 grape genotypes comprising a mixture of ancient cultivars, landraces, and modern varieties collected worldwide were genotyped with genotyping-by-sequencing using a genome-wide association approach based on 32,311 single-nucleotide polymorphism (SNP) markers. Genome-wide efficient mixed-model association was selected as the optimal statistical model based on the results of known control loci of grape berry color traits. Many of the associated SNPs identified in this study were in accordance with the previous QTL analyses using biparental mapping. The grape skin color locus was found to be associated with a mybA transcription factor on chromosome 2. Two strong and distinct association signals associated with berry development periods were found on chromosome 16. Most candidate genes of the interval were highlighted as receptor-like protein kinase. For berry weight, significant association loci were identified on chromosome 18, as previously known, and on chromosome 19 and chromosome 17, as newly mapped. Berry flesh texture was newly located on chromosome 16; candidate genes in the interval were related to calcium. Berry flavor was determined on chromosome 5. Genomic regions were further investigated to reveal candidate genes. In this work, we identified interesting genetic determinants of grape berry-related traits. The identification of the markers closely associated with these berry traits may be useful for grape molecular breeding. Grapes: The genetic basis of fruit traits Genetic analysis of 179 types of vine has revealed regions of the genome and associated genes and proteins that control many of the key traits in the grapes. These traits are crucial for determining fruit quality and yield, in addition to conferring flavors that are highly valued by consumers and wine makers. Researchers in China, led by Da-Long Guo at Henan University of Science and Technology, used DNA sequencing to analyze genetic markers in a mixture of ancient, traditionally cultivated and modern grape varieties. The analysis identified specific regions of the genome linked to grape fruit development, weight, texture, skin color and flavor. The molecular basis of the effects of the identified genetic regions were also explored. The findings will help generate new varieties of grapes for the food and wine industries.

This paper reports on a colorimetric assay for H 2 O 2 and glucose. It is based on the use of human serum albumin-templated MnO 2 nanosheets that possess oxidase-like activity. They are capable of oxidizing 3,3',5,5'-tetramethylbenzidine (TMB) with oxygen to give a blue product (oxTMB) with an absorbance maximum at 652 nm. When H 2 O 2 is introduced, the MnO 2 nanosheets are reduced to Mn(II) ions, and this inhibits the formation of oxTMB. Based on these findings, a colorimetric assay was established for H 2 O 2 that has a 0.56 μM detection limit. If glucose is oxidized by glucose oxidase under formation of H 2 O 2 , the nanosheets can be used to quantify H 2 O 2 and thereby to sense glucose. Response is linear in the 0.5 μM to 50 μM glucose concentration range, and the detection limit is 0.32 μM. The method was applied to the determination of glucose in spiked serum samples and gave satisficatory results. Graphical abstract Human serum albumin (HSA) is used as a template for the synthesis of MnO 2 nanosheet. These possess oxidase mimicking activity. H 2 O 2 can reduce the nanosheets. The effect is exploited in colorimetric assays for H 2 O 2 and glucose using tetramethylbenzidine (TMB) as a chromogenic substrate.

The surface water injection technology for developing low permeability reservoirs comes from the water supply of water source wells. The groundwater resources in oil fields are limited, with high water consumption and a decrease in water level, lacking effective monitoring methods. In recent years, there have been frequent occurrences of unsafe waste of electrical energy due to dry burning during pumping in water source wells, which has seriously affected the normal water injection of oilfield formations. In order to prevent dry burning of water source wells by pumping air, research on intelligent air defense dry burning technology for water source wells has been carried out. The automatic pump stop alarm at low water level and the automatic pump start at high water level avoid the phenomenon of dry burning during pumping in the water source well, ensure the normal operation of the water source well, and ensure sufficient water injection from the source. Reduce employee labor intensity and achieve the goal of optimizing human resources. Associate the start and stop status of the water source well with the tank position of the water injection station to achieve automatic water distribution and inventory, achieve digital management and fine management, and achieve the goal of reducing costs and increasing efficiency, which has promotion value.

Testosterone production by Leydig cells (LCs) plays a crucial role in male reproduction. The functional degeneration of LCs can cause testosterone deficiency, ultimately resulting in primary male hypogonadism. Transplantation of exogenous LCs with the ability to produce testosterone in response to the regulation of the hypothalamus-pituitary-gonad axis could be a promising alternative option to treat male primary hypogonadism. Recent studies have shown that it is possible to generate Leydig-like cells from stem cells by various approaches. In addition, somatic cells, such as embryonic or adult fibroblasts, have also been successfully reprogrammed into Leydig-like cells. In this review, we summarized the recent advances in the generation of Leydig-like cells, with an emphasis on comparing the effectiveness and safety of different protocols used and the cells generated. By further analyzing the characteristics of Leydig-like cells generated from fibroblasts based on small signaling molecules and regulatory factors, we found that although the cells may produce testosterone, they are significantly different from real LCs. For future in vivo applications, it is important that the steroidogenic cells generated be evaluated not only for their steroidogenic functions but also for their overall cell metabolic state by proteomics or transcriptomic tools.

The transportation of crude oil mainly relies on long-distance buried oil pipelines, which are generally made of steel pipes. Oil leakage often occurs due to corrosion, causing environmental pollution and unsafe accidents. A digital monitoring system for pulse current cathodic protection of oil pipelines was studied, with a focus on the composition and functions of the digital monitoring system for pulse current cathodic protection of oil pipelines. In 2022, the system was applied on two oil pipelines in Tongzhai operation area of the Third Oil Production Plant of Changqing oil field. The system realized the pulse current cathodic protection of oil pipelines to prevent corrosion. At the same time, it can digitally monitor the pulse current cathodic Conservation status status and adjust the working state of the potentiostat, and cooperate with the pulse current cathodic protection monitoring expert system for auxiliary analysis, which has received good economic and social benefits.

Background Osteoporosis, resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation, affects millions globally. Recent studies have identified type H vessels (CD31 hi EMCN hi ) as a specialized subset of bone blood vessels that positively regulate bone formation. This study aims to investigate the effects of metformin on bone mass, strength, and angiogenesis in osteoporotic mice, and to elucidate the underlying molecular mechanisms, particularly focusing on the YAP1/TAZ-HIF1α axis. Methods Osteoporotic mice were administered metformin, and bone mass and strength were measured. In vivo and in vitro angiogenesis assays were performed under hypoxic conditions. Expression levels of YAP1/TAZ and HIF1α were assessed in femoral metaphysis and hypoxia-cultured human microvascular endothelial cells (HMECs). Small interfering RNA was used to interfere with HIF1α or YAP1/TAZ expression in hypoxia-cultured HMECs. Additionally, we employed AAV-mediated overexpression of YAP1/TAZ in vivo to determine whether elevated YAP1/TAZ levels alter metformin’s effects on bone mass and angiogenesis. Results Metformin significantly enhanced bone mass and strength in osteoporotic mice. It also promoted angiogenesis under hypoxia conditions both in vivo and in vitro. Metformin reduced YAP1/TAZ expression while increasing HIF1α expression in both the femoral metaphysis of osteoporotic mice and hypoxia-cultured HMECs. Interference with HIF1α or YAP1/TAZ confirmed that metformin enhances HIF1α and its target genes primarily by inhibiting YAP1/TAZ. Furthermore, overexpression of YAP1/TAZ partially reversed the bone-protective effect of metformin, leading to reduced HIF1α levels and diminished type H vessel formation. Conclusion Our findings suggest that metformin holds promise as a therapeutic agent for osteoporosis by enhancing type H vessel formation through the inhibition of the YAP1/TAZ-HIF1α axis. Graphical abstract

Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells (HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using siRNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition. Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.