Pseudohypoparathyroidism Type IB with Subclinical Hypothyroidism: a Pedigree Investigation and Literature Review.

Pseudohypoparathyroidism (PHP) is a rare genetic disease characterized by hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) in serum. Here, we report a case of a patient with pseudohypoparathyroidism type IB (PHPIB) and subclinical hypothyroidism, analyze the clinical and genetic data of his family members, review the relevant literature, and classify and discuss the pathogenesis and clinical characteristics of each subtype. Finally, we discuss the treatment approach to improve clinicians' understanding of the disease.

Mechanistic insights into the changes of biological activity and physicochemical characteristics in Lacticaseibacillus paracasei fortified milk powder during storage.

To clarify the change mechanism of biological activity and physicochemical characteristics in Lacticaseibacillus paracasei JY025 fortified milk powder (LFMP) during storage, morphological observation, JY025 survival, storage stability, and metabolomics of LFMP were determined during the storage period in this study. The results showed that the LFMP had a higher survival rate of JY025 compared with the bacterial powder of JY025 (LBP) during storage, which suggested that milk powder matrix could reduce strain JY025 mortality under prolonged storage in the LFMP samples. The fortification of strain JY025 also affected the stability of milk powder during the storage period. There was lower water activity and higher glass transition temperature in LFMP samples compared with blank control milk powder (BCMP) during storage. Moreover, the metabolomics results of LFMP indicated that vitamin degradation, Maillard reaction, lipid oxidation, tricarboxylic acid cycle, and lactobacilli metabolism are interrelated and influence each other to create complicated metabolism networks.

Antimicrobial resistance profiles of common mastitis pathogens on large Chinese dairy farms.

The primary objective of this study was to determine the antimicrobial resistance (AMR) profile of common mastitis pathogens on large Chinese dairy farms. A total of 673 isolates, including Staphylococcus aureus (14.41%, 97/673), coagulase-negative staphylococci (CNS, 52.30%, 352/673), Streptococcus agalactiae (5.64%, 38/673), non-agalactiae streptococci (7.42%, 50/673), Acinetobacter spp. (7.72%, 52/673), Escherichia spp. (6.39%, 43/673), and Klebsiella spp. (6.09%, 41/673), were collected from 15 large Chinese dairy farms in 12 provinces. The AMR profiles were measured using a microdilution method. Our results showed that more than 75% of Staph. aureus (87/97) and CNS (291/352) were resistant to penicillin (PEN). More than 30% of Escherichia spp. (15/43) showed resistance to ampicillin (AMP). However, less than 10% CNS and non-agalactiae streptococci showed resistance to amoxicillin/clavulanate (AMC; 1/352; 0/50), cephalexin (LEX; 1/352; 0/50), ceftiofur (EFT; 10/352; 0/50), and rifaximin (RIX; 21/352; 2/50); less than 10% Staph. aureus showed resistance to AMC (1/97), oxacillin (OX; 3/97), LEX (1/97), EFT (2/97), and RIX (2/97); less than 10% Strep. agalactiae showed resistance to PEN (3/38), AMC (0/38), LEX (0/38), EFT (0/38), and RIX (0/38); and less than 10% Escherichia spp. showed resistance to AMC (1/43) and EFT (4/43). These results suggested that most mastitis pathogens were susceptible to most antimicrobials with exceptions of Staph. aureus tested against penicillin or ampicillin and CNS against penicillin or oxacillin. To control the AMR threat in Chinese dairy farms, a nationwide surveillance program for AMR of bovine mastitis pathogens is needed.

Effect of Thermostable Enzymes Produced by Psychrotrophic Bacteria in Raw Milk on the Quality of Ultra-High Temperature Sterilized Milk.

Ultra-high temperature sterilized milk (UHT) is a popular dairy product known for its long shelf life and convenience. However, protein gel aging and fat quality defects like creaming and flavor deterioration may arise during storage. These problems are primarily caused by thermostable enzymes produced by psychrotrophic bacteria. In this study, four representative psychrotrophic bacteria strains which can produce thermostable enzymes were selected to contaminate UHT milk artificially. After 11, 11, 13, and 17 weeks of storage, the milk samples, which were contaminated with Pseudomonas fluorescens, Chryseobacterium carnipullorum, Lactococcus raffinolactis and Acinetobacter guillouiae, respectively, demonstrated notable whey separation. The investigation included analyzing the protein and fat content in the upper and bottom layers of the milk, as well as examining the particle size, Zeta potential, and pH in four sample groups, indicating that the stability of UHT milk decreases over time. Moreover, the spoiled milk samples exhibited a bitter taste, with the dominant odor being attributed to ketones and acids. The metabolomics analysis revealed that three key metabolic pathways, namely ABC transporters, butanoate metabolism, and alanine, aspartate, and glutamate metabolism, were found to be involved in the production of thermostable enzymes by psychrotrophic bacteria. These enzymes greatly impact the taste and nutrient content of UHT milk. This finding provides a theoretical basis for further investigation into the mechanism of spoilage.

CO2-Triggered Hierarchical-Pore UiO-66-Based Pickering Emulsions for Efficient and Recyclable Suzuki-Miyaura Cross-Coupling in Biphasic Systems.

Hierarchical-pore metal-organic frameworks (H-MOFs) are considered to be emerging stabilizers for Pickering emulsion formation because of their hierarchically arranged pores, tailorable structures, and ultrahigh surface areas. However, stimulus-triggered Pickering emulsions built by H-MOFs have been seldom presented to date despite their great significance in diverse applications. Herein, by grafting Pd(OAc)2 on the hierarchical-pore zirconium MOF UiO-66, namely, H-UiO-66, with the aid of 1-alkyl-3-methylimidazolium 2-cyanopyrrolide salts ([CnMIM][2-CN-Pyr], n = 4, 6, and 8), a series of Pd(OAc)2-[CnMIM][2-CN-Pyr]@H-UiO-66 have been developed and utilized as emulsifiers for constructing CO2-switching Pickering emulsions. It was found that Pd(OAc)2-[CnMIM][2-CN-Pyr]@H-UiO-66 was able to stabilize the n-hexane-water mixture to form a Pickering emulsion even at an amount of 0.5 wt %. Upon alternate addition of CO2 and N2 at normal pressure, Pickering emulsions could be smartly converted between demulsification and re-emulsification. Through combining varieties of spectroscopic techniques, the mechanism of the switchable phase transformation lay in the acid-base reaction of ionic liquids with CO2 on H-UiO-66 and the creation of more hydrophilic salts, which reduced the wettability of the emulsifier and destabilized the emulsion. As an example of application, the stimulus-triggered Pickering emulsion was employed as a palladium-catalyzed Suzuki-Miyaura cross-coupling microreactor to achieve the combination of chemical reactions, isolation of products, and recovery of catalysts.

Long Non-coding RNA ZFAS1 Regulates Fibrosis and Scortosis in the Cell Model of Diabetic Nephropathy Through miR-525-5p/SGK1 Axis.

Diabetic nephropathy (DN) is a common clinical syndrome in diabetic patients. Functional characterization of non-coding (ncRNAs) involved in the progression of DN can provide insights into the diagnosis and therapeutic management of DN. Human kidney proximal tubular epithelial cells (HK-2) were challenged by high glucose (HG, 50 mM) as a cell model of DN. The expression level of long non-coding RNA (lncRNA) ZFAS1 was quantified by qRT-PCR. The proteins and cytokines related to fibrosis and scortosis in DN (NLRP3, GSDMD-N, IL-1ß and Caspase 1, fibronectin, collagen I, collagen III, IL-1ß, and IL-18) were examined by western blot or ELISA. RNA precipitation and luciferase reporter activity experiments were conducted to assess the molecular associations. ZFAS1 and SGK1 were highly induced in HK-2 cells challenged with HG, while miR-525-5p downregulated upon HG treatment. ZFAS1 knockdown attenuated HG-induced fibrosis and scortosis in HK-2 cells by reducing the levels of NLRP3, GSDMD-N, Caspase 1, fibronectin, collagen I/III, IL-1ß, and IL-18. Mechanically, ZFAS1 knockdown protected HK-2 cells from HG-induced injury by upregulating miR-525-5p and repressing SGK1 expression. Overall, our results suggest that knocking down ZFAS1 may be formulated as a protective strategy in ameliorating DN progression through regulating miR-525-5p/SGK1 pathway. Targeting ZFAS1 could be further explored as a potential approach for the management of DN.

Evaluation of milk photooxidation based on peptidomics.

Photooxidation is one of the main causes of the deterioration of milk quality during processing and marketing. This study aimed to investigate the variation in peptides after photooxidation using peptidomic techniques, and how cow species, oxygen content, and light intensity affect photooxidation. The different peptides were identified and quantified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Eighteen milk samples were subjected to light treatment. Seven types of peptides were identified as photooxidation markers. Subsequently, the effects of milk variety, oxygen content, and light intensity on photooxidation were studied, and sensory evaluations were performed. Dairy cow breed, oxygen content, and light intensity all affect photooxidation. Sensory evaluation verified that light and oxygen are necessary for the photooxidation of milk. The peptide m/z+ 529.2783 (LLDEIKEVV), both in different varieties of milk and in different brands of commercially available milk, showed a large variation in multiplicity, and its content was closely related to oxygen and light. This peptide was not produced in the absence of oxygen and light, and its relative content increased with the duration of light exposure. These results suggest that the peptidomics method is an effective tool for distinguishing between normal and photooxidized milk.

Profile analysis of differentially expressed long non­coding RNAs in metabolic memory induced by high glucose in human umbilical vein endothelial cells.

Numerous long non-coding RNAs (lncRNAs) are dysregulated in the hyperglycemia-induced phenomenon of metabolic memory (MM). In the present study, the significance of these lncRNAs in MM was explored by screening for MM-involved differentially expressed lncRNAs (MMDELs) in human umbilical vein endothelial cells (HUVECs) induced by high glucose. A total of nine HUVEC samples were divided into three groups to mimic conditions of low and high glucose environments, as well as induce the state of metabolic memory. The expression of lncRNAs was profiled using RNA sequencing. Bioinformatic analysis was performed using the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases to explore the parental genes from which the lncRNAs are transcribed and target genes of the MMDELs and generate enrichment datasets. Reverse transcription-quantitative PCR was performed to validate the expression levels of the selected lncRNAs. The present study identified 308 upregulated and 157 downregulated MMDELs, which were enriched in numerous physiologic processes. Key functional enrichment terms included 'cell cycle', 'oocyte meiosis' and 'p53 signaling pathway'. In conclusion, certain MMDELs may regulate the expression level of highly associated mRNAs through various mechanisms and pathways, thereby interfering with several processes, such as the regulation of the cell cycle, and affecting vascular endothelial cell function. Furthermore, the disorders of these lncRNAs can be retained in MM, further investigation into the functions of these lncRNAs may result in novel insights and treatments, which could help control MM in patients with diabetes.

Circular RNA COL1A2 Mediates High Glucose-Induced Oxidative Stress and Pyroptosis by Regulating MiR-424-5p/SGK1 in Diabetic Nephropathy.

Diabetic nephropathy (DN) represents a major diabetes-related complication, which could undermine renal function. CircCOL1A2 has been previously reported to show abnormal expression during DN. However, its functional role in the progression of DN, as well as the potential molecular mechanisms, remains unclear. The present work examined the expression of circCOL1A2 in the plasma of DN patients, and employed high glucose (HG)-challenged HK-2 cells as the in vitro cell model of hyperglycemia (HG)-induced DN. CircCOL1A2 was silenced using siRNA in HK-2 cells to clarify the functional engagement of circCOL1A2 in HG-induced DN. We examined the roles of circCOL1A2 in regulating oxidative stress by measuring reactive oxygen species (ROS), lipid peroxidation, and superoxide dismutase (SOD) levels. Besides, the effects of circCOL1A2 silencing on pyroptosis were investigated by RT-qPCR, western blot (WB), and ELISA assays. StarBase (version 2.0) was used to identify the downstream effector of circCOL1A2, and their interactions were further verified through dual-luciferase reporter analysis, RNA pull-down assays, and RNA immunoprecipitation (RIP) assay. CircCOL1A2 was highly expressed in DN patients and HG-induced HK-2 cells. Knocking down circCOL1A2 alleviated oxidative stress and pyroptosis upon HG treatment. In addition, we demonstrated that circCOL1A2 knockdown could promote miR-424-5p expression while inhibiting Serum/Glucocorticoid Regulated Kinase 1 (SGK1) level. Furthermore, miR-424-5p inhibitor or SGK1 overexpression impaired the effects of circCOL1A2 knockdown on HG-induced oxidative stress and pyroptosis. Hence, our results demonstrated that the circCOL1A2 mediates HG-exposed pyroptosis and oxidative stress through modulating miR-424-5p/SGK1 axis in diabetic nephropathy, indicating that silencing circCOL1A2 is a potential intervention strategy for DN management.

CO2-Switchable Hierarchically Porous Zirconium-Based MOF-Stabilized Pickering Emulsions for Recyclable Efficient Interfacial Catalysis.

Stimuli-responsive Pickering emulsions are recently being progressively utilized as advanced catalyzed systems for green and sustainable chemical conversion. Hierarchically porous metal-organic frameworks (H-MOFs) are regarded as promising candidates for the fabrication of Pickering emulsions because of the features of tunable porosity, high specific surface area and structure diversity. However, CO2-switchable Pickering emulsions formed by hierarchically porous zirconium-based MOFs have never been seen. In this work, a novel kind of the amine-functionalized hierarchically porous UiO-66-(OH)2 (H-UiO-66-(OH)2) has been developed using a post-synthetic modification of H-UiO-66-(OH)2 by (3-aminopropyl)trimethoxysilane (APTMS), 3-(2-aminoethylamino)propyltrimethoxysilane (AEAPTMS) and 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane (AEAEAPTMS), and employed as emulsifiers for the construction of Pickering emulsions. It was found that the functionalized H-UiO-66-(OH)2 could stabilize a mixture of toluene and water to give an emulsion even at 0.25 wt % content. Interestingly, the formed Pickering emulsions could be reversibly transformed between demulsification and re-emulsification with alternate addition or removal of CO2. Spectral investigation indicated that the mechanism of the switching is attributed to the reaction of CO2 with amino silane on the MOF and the generation of hydrophilic salts, leading to a reduction in MOF wettability. Based on this strategy, a highly efficient and controlled Knoevenagel condensation reaction has been gained by using the emulsion as a mini-reactor and the emulsifier as a catalyst, and the coupling of catalysis reaction, product isolation and MOF recyclability has become accessible for a sustainable chemical process.

The changes in peripheral blood Th17 and Treg ratios in Hashimoto's thyroiditis are accompanied by differential PD-1/PD-L1 expression.

Objective: The aim of this study was to analyze the percentages of T helper 17 cells (Th17s) and T regulatory cells (Tregs) in autoimmune Hashimoto's thyroiditis (HT), and the expression of the checkpoint molecules programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) on these cells. Methods: This is a case-control study involving 53 initially diagnosed HT patients (HT group) and 21 normal controls (NC group). The peripheral blood mononuclear cells from the individuals of the two groups were isolated and restimulated ex vivo; the percentage of Th17s, Tregs, PD-1+ Th17s, PD-L1+ Th17s, PD-1+ Tregs, and PD-L1+ Tregs was assessed by flow cytometric analysis. Results: (1) The percentage of Th17s in the peripheral blood of the HT group was significantly higher than that of the NC group [(6.38 ± 1.32)% versus (3.12 ± 0.66)%; t = 14.110, P < 0.001], while the percentage of peripheral blood Tregs was significantly lower [(3.82 ± 1.48)% versus (5.61 ± 1.60)%; t = -4.599, P < 0.001]. (2) HT patients' Th17s expressed PD-1 at a significantly lower frequency than their counterparts in the NC [(6.46 ± 2.77)% versus (18.51 ± 3.96)%; t = -14.842, P < 0.001], while no difference was observed for PD-L1 between the two groups. (3) In contrast, both PD-1 and PD-L1 were expressed at significantly higher frequency on HT patients' Tregs than on NC [respectively: (17.01 ± 3.04)% versus (10.23 ± 2.77)%; t = 8.850, P < 0.001 for PD-1; (16.60 ± 9.58)% versus (11.36 ± 10.14)%; t = 2.089, P < 0.005, for PD-L1]. Conclusion: (1) The increased percentage of Th17s and decreased percentage of PD-1+ Th17s in the HT group suggest that a loss of control on Th17 activity through the checkpoint inhibitory axis PD-1/PD-L1 may participate in disease pathogenesis. (2) While the decreased percentage of Tregs in HT patients may explain a lack of regulatory functions able to prevent the autoimmune destruction of the thyroid, the significance of the increased frequency of Tregs expressing PD-1 and PD-L1, previously reported to boost Tregs differentiation, remains to be established. Elucidating this apparent contradiction may reveal important mechanisms underlying HT pathogenesis.

High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes.

The aims of the present study were to evaluate the expression of prolyl 4-hydroxylase subunit alpha 3 (P4HA3) in adipocytes and adipose tissue and to explore its effect on obesity and type 2 diabetes mellitus (T2DM). We initially demonstrated that P4HA3 was significantly upregulated in the subcutaneous adipose tissue of obesity and T2DM patients, and its functional roles in adipocyte differentiation and insulin resistance were investigated using in vitro and in vivo models. The knockdown of P4HA3 inhibited adipocyte differentiation and improved insulin resistance in 3T3-L1 cells. In C57BL/6J db/db mice fed with a high fat diet (HFD), silencing P4HA3 significantly decreased fasting blood glucose and triglycerides (TG) levels, with concomitant decrease of body weight and adipose tissue weight. Further analysis showed that P4HA3 knockdown was correlated with the augmented IRS-1/PI3K/Akt/FoxO1 signaling pathway in the adipose and hepatic tissues of obese mice, which could improve hepatic glucose homeostasis and steatosis of mice. Together, our study suggested that the dysregulation of P4HA3 may contribute to the development of obesity and T2DM.

CO2-Driven reversible transfer of amine-functionalized ZIF-90 between organic and aqueous phases.

Phase transfer of metal-organic frameworks is highly desired in many areas, which remains a challenge. Herein, we present for the first time a CO2-driven reversible transfer of amine-functionalized ZIF-90 between organics and water. A mechanistic study showed that the switching is ascribed to the reversible generation of hydrophilic ammonium salts from the reaction of CO2 with the amines on ZIF-90. This unique system has been used for the coupling of trans-esterification reactions, product separation and component recycling for green sustainable processes. This work opens up a new avenue for performing reactions effectively with an easy separation process.

TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2.

TSPAN8 mediates signal transduction from extracellular cues and regulates cell development, activation, growth, and motility. However, whether TSPAN8 is involved in the progression of diabetic nephropathy (DN) remains unclear. This study aimed to explore the potential functional roles of TSPAN8 in regulating autophagy and apoptosis of HK-2 cells induced by high glucose (HG). RT-PCR and western blot analysis (WB) were employed to detect TSPAN8 levels in the blood samples of DN patients as well as in HG-induced HK-2 cells. Cell proliferation of HK-2 cells was examined by CCK-8 assay, and apoptosis was analyzed by flow cytometry. The functional role of TSPAN8 was evaluated by the transfection of TSPAN8 expression plasmid. Results showed that TSPAN8 level was significantly reduced in the blood samples of DN patients and HG-induced HK-2 cell lines. TSPAN8 overexpression rescued HG-induced apoptosis in HK-2 cells. TSPAN8 could form a complex with Rictor and mTORC2. TSPAN8 overexpression suppressed HG-induced autophagy in HK-2 cells, which was dependent on mTOR activity. In conclusion, the present study showed that TSPAN8 mitigates HG-induced autophagy and apoptosis in HK-2 cells, which may serve as candidate target for DN treatment.

[Microbial contamination in dried fruit products in China in 2019].

OBJECTIVE: To investigate the microbial contamination in dried fruit products in China. METHODS: In 2019, 2917 samples of dried fruit products on the market were collected, and examined for aerobic bacterial count, coliforms, molds, yeasts, Salmonella and Listeria monocytogenes according to the method specified in GB 4789. RESULTS: A total of 34.42%(1004/2917)of the samples had molds above 50 CFU/g and 9.46%(276/2917)of the samples had yeast above 50 CFU/g. The occurrence of aerobic plate count above 10~4 CFU/g and coliforms above 10~2 CFU/g was 5.01%(146/2917)and 2.98%(87/2917), respectively. The detection rate of Salmonella and Listeria monocytogenes were 0.14%(4/2917) and 0.03%(1/2917), respectively. Microbial contamination in different kinds of dried fruit products varied widely, with dried wolfberries and dried durian having the worst overall hygiene. There were differences in microbial contamination of dried fruit products in different regions. In general, samples collected in South China, Southwest China and Central China had more serious microbial contamination. There was no significant difference in microbial contamination between dried fruit products with different packaging and sampling places. CONCLUSION: The hygienic condition of dried fruit products is generally poor in 2019.

miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8.

BACKGROUND: Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which can lead to renal failure and fatality. miRNAs are an important class of endogenous non-coding RNAs implicated in a wide range of biological processes and pathological conditions. This study aims to investigate the potential functional roles of miR-543 in DN and its underlying mechanisms. METHODS: qRT-PCR was performed to detect the expression levels of miR-543 and TSPAN8 in kidney tissues of mice with DN. Western blot (WB) was used to measure the protein levels. CCK8 assay was employed to evaluate the proliferation of HK2 cells. Dual luciferase reporter assay was conducted to verify the functional interaction between miR-543 and TSpan8. RESULTS: The downregulation of miR-543 and upregulation of TSPAN8 were observed in kidney tissues of mice with DN. miR-543 mimic significantly decreased cell proliferation and autophagy in high-glucose (HG)-induced HK2 cells, and promoted cell fibrosis. We further identified a putative binding site between miR-543 and TSPAN8, which was validated by Dual luciferase reporter assay. The treatment of miR-543 mimic and miR-543 inhibitor could reduce or increase TSPAN8 protein level respectively. We further showed that the overexpression of TSPAN8 could attenuate HG-induced cell injury by reducing fibrosis and increase autophagy. The effects of miR-543 mimic in proliferation, fibrosis, and autophagy were rescued by TSPAN8 overexpression. CONCLUSIONS: Our study indicate that miR-543 mediates high-glucose induced DN via targeting TSPAN8. Interfering miR-543/TSPAN8 axis could serve as potential approach to ameliorate DN.

Population genomics of the food-borne pathogen Vibrio fluvialis reveals lineage associated pathogenicity-related genetic elements.

Vibrio fluvialis is a food-borne pathogen with epidemic potential that causes cholera-like acute gastroenteritis and sometimes extraintestinal infections in humans. However, research on its genetic diversity and pathogenicity-related genetic elements based on whole genome sequences is lacking. In this study, we collected and sequenced 130 strains of V. fluvialis from 14 provinces of China, and also determined the susceptibility of 35 of the strains to 30 different antibiotics. Combined with 52 publicly available V. fluvialis genomes, we inferred the population structure and investigated the characteristics of pathogenicity-related factors. The V. fluvialis strains exhibited high levels of homologous recombination and were assigned to two major populations, VflPop1 and VflPop2, according to the different compositions of their gene pools. VflPop2 was subdivided into groups 2.1 and 2.2. Except for VflPop2.2, which consisted only of Asian strains, the strains in VflPop1 and VflPop2.1 were distributed in the Americas, Asia and Europe. Analysis of the pathogenicity potential of V. fluvialis showed that most of the identified virulence-related genes or gene clusters showed high prevalence in V. fluvialis, except for three mobile genetic elements: pBD146, ICEVflInd1 and MGIVflInd1, which were scattered in only a few strains. A total of 21 antimicrobial resistance genes were identified in the genomes of the 182 strains analysed in this study, and 19 (90%) of them were exclusively present in VflPop2. Notably, the tetracycline resistance-related gene tet(35) was present in 150 (95%) of the strains in VflPop2, and in only one (4%) strain in VflPop1, indicating it was population-specific. In total, 91% of the 35 selected strains showed resistance to cefazolin, indicating V. fluvialis has a high resistance rate to cefazolin. Among the 15 genomes that carried the previously reported drug resistance-related plasmid pBD146, 11 (73%) showed resistance to trimethoprim-sulfamethoxazole, which we inferred was related to the presence of the dfr6 gene in the plasmid. On the basis of the population genomics analysis, the genetic diversity, population structure and distribution of pathogenicity-related factors of V. fluvialis were delineated in this study. The results will provide further clues regarding the evolution and pathogenic mechanisms of V. fluvialis, and improve our knowledge for the prevention and control of this pathogen.

High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes

The aims of the present study were to evaluate the expression of prolyl 4-hydroxylase subunit alpha 3 (P4HA3) in adipocytes and adipose tissue and to explore its effect on obesity and type 2 diabetes mellitus (T2DM). We initially demonstrated that P4HA3 was significantly upregulated in the subcutaneous adipose tissue of obesity and T2DM patients, and its functional roles in adipocyte differentiation and insulin resistance were investigated using in vitro and in vivo models. The knockdown of P4HA3 inhibited adipocyte differentiation and improved insulin resistance in 3T3-L1 cells. In C57BL/6J db/db mice fed with a high fat diet (HFD), silencing P4HA3 significantly decreased fasting blood glucose and triglycerides (TG) levels, with concomitant decrease of body weight and adipose tissue weight. Further analysis showed that P4HA3 knockdown was correlated with the augmented IRS-1/PI3K/Akt/FoxO1 signaling pathway in the adipose and hepatic tissues of obese mice, which could improve hepatic glucose homeostasis and steatosis of mice. Together, our study suggested that the dysregulation of P4HA3 may contribute to the development of obesity and T2DM.

The China National Foodborne Pathogen Surveillance System: Twenty Years of Experience and Achievements.

National foodborne pathogen surveillance is a system that collects data regarding food contamination by pathogenic bacteria, viruses, parasites, and other harmful microbial factors. The surveillance data are used to understand the potential microbial risks in different categories of food and to provide science-based data for risk assessment and development of reference standards in the form of maximum limits. This review introduces stepwise expansion of the foodborne pathogen surveillance in China, relevant policies, function and duties of different organizations and institutions, surveillance plans, and quality control. Achievements of the surveillance system and future challenges are also presented.

CircHIPK3 Alleviates High Glucose Toxicity to Human Renal Tubular Epithelial HK-2 Cells Through Regulation of miR-326/miR-487a-3p/SIRT1.

BACKGROUND: The intervention of circular RNA HIPK3 (circHIPK3) in diabetes has drawn increasing attention in recent years. However, the underlying mechanism of circHIPK3 in diabetic nephropathy (DN) has not been fully elucidated. Thus, the current study aims to investigate the role of circHIPK3 in high glucose (HG)-induced toxicity to human renal tubular epithelial HK-2 cells. METHODS: The expression of circHIPK3 in HK-2 cells induced by HG was determined by qRT-PCR and Western blot. The regulatory effects of circHIPK3 and miR-326/miR-487a-3p on cells proliferative and apoptosis were evaluated by CCK-8 and flow cytometry. Dual-luciferase reporter assay was applied to predict the target genes of miR-326 or miR-487a-3p. RESULTS: Expression level of circHIPK3 in HK-2 cells was remarkably decreased after the treatment of HG. The overexpression of circHIPK3 effectively reversed the HG-induced HK-2 cell proliferation inhibition and apoptosis. Furthermore, SIRT1 was confirmed to be the target gene of miR-326 and miR-487a-3p, which were showed to be the downstream genes of circHIPK3. The silencing of miR-326 or miR-487a-3p was also proved to induce proliferation and reduce apoptosis in HG-induced HK-2 cells. CONCLUSION: Our data suggest that overexpression of circHIPK3 can attenuate the proliferation inhibition of HK-2 induced by HG and inhibit apoptosis through sponging miR-326 or miR-487a-3p to regulate SIRT1.