Severity of abdominal obesity and cardiometabolic diseases in US adults.

OBJECTIVES: To determine the prevalence of cardiometabolic diseases (CMDs) among adults with abdominal obesity and to evaluate the necessity of differentiating severity of abdominal obesity. STUDY DESIGN: Cross-sectional study and prospective cohort study. METHODS: National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2020 were included for cross-sectional analyses. Class I, II and III abdominal obesity were created by dividing waist circumference within sex-specific abdominal obesity range into tertiles. Age-standardized prevalence of CMDs was estimated and differences by severity of abdominal obesity were compared using Poisson regressions. Prospective analyses were performed using NHANES data between 1988 and 2018 with linked mortality data. Cox proportional hazards models were used to assess the association between severity of abdominal obesity and mortality. RESULTS: Among 23,168 adults included (mean age: 47.8 years, 49.3% men), 13,307 (57.4%) had abdominal obesity. Among adults with abdominal obesity, the estimated prevalence of diabetes was 17.3% (95% confidence interval: 16.3%, 18.2%), hypertension 39.3% (38.2%, 40.3%), dyslipidemia 59.5% (58.0%, 61.1%), cardiovascular disease 9.0% (8.3%, 9.8%), chronic kidney disease 16.8% (15.9%, 17.7%) and non-alcoholic fatty liver disease 39.9% (38.4%, 41.4%). The estimated prevalence was 55.5% (53.8%, 57.2%) for having ≥2 CMDs. Compared with class I abdominal obesity, class III abdominal obesity was related to a 43%-184% higher prevalence of CMDs and a 44% higher risk of all-cause mortality. CONCLUSIONS: The prevalence of CMDs was high and multimorbidity of CMDs was common among US adults with abdominal obesity. The prevalence of CMDs and risk of mortality differed significantly by severity of abdominal obesity.

Exome-wide screening identifies novel rare risk variants for bone mineral density.

Bone mineral density (BMD) is an independent risk factor of osteoporosis-related fractures. We performed gene-based burden tests to assess the association between rare variants and BMD, and identified several BMD candidate genes. PURPOSE: BMD is highly heritable and a major predictor of osteoporotic fractures, but its genetic basis remains unclear. We aimed to identify rare risk variants contributing to BMD. METHODS: Utilizing the newly released UK Biobank 200,643 exome dataset, we conducted a gene-based exome-wide association study in males and females, respectively. First, 100,639 males and 117,338 females with BMD values were included in the polygenic risk scores (PRS) analysis. Among individuals with lower 30% PRS, cases were individuals with top 10% BMD, and individuals with bottom 10% BMD were the controls. Considering the effects of vitamin D (VD), individuals with the highest 30% VD concentration were selected for VD-BMD analysis. After quality control, 741 males and 697 females were included in the BMD analysis, and 717 males and 708 females were included in the VD-BMD analysis. The variants were annotated by ANNOVAR software, then BMD and VD-BMD qualified variants were imported into the SKAT R-package to perform gene-based burden tests, respectively. RESULTS: The gene-based burden test of the exonic variants identified genome-wide candidate associations in ANKRD18A (P = 1.60 × 10-5, PBonferroni adjust = 2.11 × 10-3), C22orf31 (P = 3.49 × 10-4, PBonferroni adjust = 3.17 × 10-2), and SPATC1L (P = 1.09 × 10-5, PBonferroni adjust = 8.80 × 10-3). For VD-BMD analysis, three genes were associated with BMD, such as NIPAL1 (P = 1.06 × 10-3, PBonferroni adjust = 3.91 × 10-2). CONCLUSIONS: Our study suggested that rare variants contribute to BMD, providing new sights for broadening the genetic structure of BMD.

Plaster board waste (PBW) - A potential fluoride leaching source in soil/water environments and, fluoride immobilization studies using soils.

Plaster board waste generated from industries, usually contains major proportion of calcium as calcium sulfate. In addition, fluoride is remarkably one among the constituents of this waste material which leaches off into the soil and aquatic environments and causes fluoride pollution. In order to simulate how the dumping of PBW causes fluoride contamination in soil and water sources, shaking and stirring based batch-mode leaching studies were conducted. These studies explored the leaching of fluoride as a function of particle size, agitation time, pH of the leaching solvent (distilled water), L/S (water: PBW) ratio, temperature and electrolytes. It was explored that 1 g of plaster board waste contains18.54 mg F per gram of PBP. High leaching of 3.72 mg F per liter was studied at pH 6.02 with Ca2+ and TDS contents of 1050 mg L-1 and1640 mg L-1 respectively. The influence of sodium electrolytes such as chloride, nitrate, hydrogen carbonate, carbonate, sulfate, borate, phosphate and acetate on the leaching of fluoride from PBW was studied. The influence of fluoride leaching by sodium phosphate recorded a high value of 12.75 mg L-1 with no detectable amount of calcium ions. The influence of eight electrolytic mixtures each containing five sodium electrolytes on fluoride leaching corroborated the highest leaching in mixtures containing phosphate followed by hydrogen carbonate/carbonate. Solutions of calcium and aluminium chloride and their mixture were used to measure the rate of leachable fluoride in solution. Furthermore, the fluoride leaching at different temperatures and acids was studied. Naturally occurring soils when blended with PBW were observed to immobilize fluoride and lessened the amount of leaching fluoride in water. Various characterization studies such as FTIR, Raman, FESEM (with EDS), XRD and XPS were carried out for PBW and its treated samples using different electrolytes. Fluoride leaching proportionate to the precipitation of carbonate and phosphate was recorded in the case of appropriate electrolyte and mixtures.

[Effects of Peroxisome Proliferator-Activated Receptor γ on Modulating Angiopoietin-Like Protein 4 Synthesis in Caco-2 Cells Exposed to Clostridium butyricum].

Angiopoietin-like protein 4 (ANGPTL4) is considered to be one of the important circulating mediators linking intestinal microorganisms and host lipid metabolism. The objective of this study was to assess the effects of peroxisome proliferator-activated receptor у (PPARγ) on modulating ANGPTL4 synthesis in Caco-2 cells exposed to Clostridium butyricum. The viability of Caco-2 cells and the expression of PPARγ and ANGPTL4 in Caco-2 cells were detected after the Caco-2 cells were co-cultured with C. butyricum at the concentration of 1 x 10^(6), 1 x 10^(7) and 1 x 10^(8) CFU/mL. The results showed that cell viability was enhanced by C. butyricum. Besides, PPARγ and ANGPTL4 expression and secretion in Caco-2 cells was significantly increased by 1 x 10^(7) and 1 x 10^(8) CFU/mL of C. butyricum. Furthermore, the effects of PPARγ on modulating ANGPTL4 synthesis in Caco-2 cells regulated by 1 x 10^(8) CFU/mL of C. butyricum was also be expounded in PPARγ activation/inhibition model based on Caco-2 cells and via ChIP technique. It was found that C. butyricum promoted the binding of PPARγ to the PPAR binding site (chr19: 8362157-8362357, located upstream of the transcriptional start site of angptl4) of the angptl4 gene in Caco-2 cells. However, the PPARγ was not the only way for C. butyricum to stimulate ANGPTL4 production. Taken together, PPARγ played a role in the regulation of ANGPTL4 synthesis by C. butyricum in Caco-2 cells.

CCDC3 Gene Regulates the Proliferation of Breast Cancer Cells.

We studied the effect of CCDC3 on the viability of human breast cancer cell line MDA-MB-231. The levels of CCDC3 mRNA and the corresponding protein in MDA-MB-231, MCF-7, T-47D, and HCC1937 cell lines were measured by reverse transcription quantitative real-time PCR and Western blotting. Since MDA-MB-231 cells had higher expression of mRNA CCDC3 and CCDC3 protein, we used this cell line for transfection with small interfering RNA by lentivirus. Cell Counting Kit-8 and clone formation assay were used to detect the effects of CCDC3 knockdown on cell viability; flow cytometry was used to detect the effects of CCDC3 knockdown on cell apoptosis and cell cycle. In MDA-MB-231 cell line, the CCDC3 protein level was significantly down-regulated after CCDC3 knockdown in comparison with the control group (p<0.05). The cell viability and the number of clones in the CCDC3 knockdown group were significantly reduced (p<0.05), while the apoptosis rate significantly increased (p<0.05). Thus, after CCDC3 knockdown, cell viability is weakened in MDA-MB-231 cells, and cell apoptosis rate is increased. Therefore, CCDC3 gene is promising as a new candidate target for BC treatment.

[Clinicopathological analysis of nuclear protein in testis midline carcinoma].

Objective: To investigate the clinicopathological features, immunophenotype and prognosis of nuclear protein in testis (NUT) midline carcinoma. Methods: Twenty-four resection cases of NUT midline carcinoma diagnosed at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China from January 2018 to September 2022, were collected, and retrospectively analyzed for their clinicopathological characteristics. Relevant literature was reviewed. Results: All 24 cases of NUT midline carcinoma occurred in the chest or head and neck, including 14 men and 10 women, with a median age of 40 years. Histological examination showed that the tumors were poorly differentiated, with solid nested or sheet-like arrangement, small to medium-sized cells, sparse cytoplasm and coarse granular chromatin, including 5 cases with abrupt squamous epithelial differentiation. Immunohistochemistry showed that all 24 cases were positive for NUT protein, while 16 cases were p63 positive, 19 cases were p40 positive, 15 out of 18 cases were CK5/6 positive. Follow-up data were obtained for 21 patients (follow-up time range, 1-21 months), of which 11 survived, 10 died, and 3 were lost to follow-up. Conclusions: NUT midline carcinoma is a rare and highly aggressive malignancy with unique histological, immunophenotypic and molecular features. It has a poor prognosis.

Epidemiology of resistance of carbapenemase-producing Klebsiella pneumoniae to ceftazidime-avibactam in a Chinese hospital.

AIMS: Klebsiella pneumoniae has been reported to develop increased antibiotic resistance. Ceftazidime-avibactam (CZA) is a novel antibiotic with activity against serine-lactamase. Here, we investigated the sensitivity of carbapenem-resistant K. pneumoniae (CRKP) to CZA and the mechanisms of drug resistance in our hospital. METHODS AND RESULTS: Patient characteristics were obtained from medical records. K. pneumoniae and its antibiotic susceptibility were determined using the Vitek-2 Compact instrument. The antibiotic resistance genes KPC, NDM, OXA-48, VIM, IMP, CIM, SPM, TMB, SMB, SIM, AIM and DIM were detected using real-time PCR. Multilocus sequence typing was used for genetic RELATEDNESS analysis. In total, 121 CRKP strains were isolated from patients in the intensive care unit (51·2%), senior ward (12·4%) and neurosurgery department (10%). With an average age of 72·5 years, most patients were in care for respiratory (34·7%), brain (20·7%), digestive tract (13·2%) and cardiovascular (8·3%) diseases. Specimens were predominantly obtained from sputum (39·67%), urine (29·75%) and blood (6·61%). CONCLUSION: Of 23 CZA-resistant CRKP strains (19·01%), ST11 being the most common at 56·52%, 11 NDM-1-positive (47·83%) and four NDM-5-positive (17·39%) strains were detected. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study indicates that CZA resistance occurs in ~19·01% CRKP strains and that blaNDM-1 and blaNDM-5 might be critical for resistance.

Preoperative gadoxetic acid-enhanced MRI predicts aggressive pathological features in LI-RADS category 5 hepatocellular carcinoma.

AIM: To investigate whether Liver Imaging Reporting and Data System (LI-RADS) imaging features and non-LI-RADS imaging features can predict aggressive pathological features in adult patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From February 2018 to September 2021, 236 adult patients with cirrhosis or hepatitis B virus infection in which liver cancer was suspected underwent MRI within 1 month before surgery. Significant MRI findings and alpha-fetoprotein (AFP) level predicted high-grade HCC and microvascular invasion (MVI) by univariate and multivariate logistic regression models. RESULTS: The study included 112 patients with histopathologically confirmed liver cancer (≤5 cm), 35 of whom (31.3%) high-grade HCC and 42 of 112 (37.5%) patients had MVI. Mosaic architecture (odds ratio [OR] = 6.031; 95% confidence interval [CI]: 1.366, 26.626; p=0.018), coronal enhancement (OR=5.878; 95% CI: 1.471, 23.489; p=0.012), and intratumoural vessels (OR=5.278; 95% CI: 1.325, 21.020; p=0.018) were significant independent predictors of high-grade HCC. A non-smooth tumour margin (OR=10.237; 95% CI: 1.547, 67.760; p=0.016), coronal enhancement (OR=3.800; 95% CI: 1.152, 12.531; p=0.028), and peritumoural hypointensity on the hepatobiliary phase (HBP; OR=10.322; 95% CI: 2.733, 38.986; p=0.001) were significant independent predictors of MVI. CONCLUSION: In high-risk adult patients with single LR-5 HCC (≤5 cm), mosaic architecture, coronal enhancement, and intratumoural vessels are independent predictors of high-grade HCC. Non-smooth tumour margin, coronal enhancement, and peritumoural hypointensity on HBP independently predicted MVI.

Research progress on the regulation mechanism of probiotics on the microecological flora of infected intestines in livestock and poultry.

The animal intestine is a complex ecosystem composed of host cells, gut microbiota and available nutrients. Gut microbiota can prevent the occurrence of intestinal diseases in animals by regulating the homeostasis of the intestinal environment. The intestinal microbiota is a complex and stable microbial community, and the homeostasis of the intestinal environment is closely related to the invasion of intestinal pathogens, which plays an important role in protecting the host from pathogen infections. Probiotics are strains of microorganisms that are beneficial to health, and their potential has recently led to a significant increase in studies on the regulation of intestinal flora. Various potential mechanisms of action have been proposed on probiotics, especially mediating the regulation mechanism of the intestinal flora on the host, mainly including competitive inhibition of pathogens, stimulation of the host's adaptive immune system and regulation of the intestinal flora. The advent of high-throughput sequencing technology has given us a clearer understanding and has facilitated the development of research methods to investigate the intestinal microecological flora. This review will focus on the regulation of probiotics on the microbial flora of intestinal infections in livestock and poultry and will depict future research directions.

Ingroup vigilance in collectivistic cultures.

Collectivistic cultures have been characterized as having harmonious, cooperative ingroup relationships. However, we find evidence that people in collectivistic cultures are more vigilant toward ingroup members, mindful of their possible unethical intentions. Study 1 found that Chinese participants were more vigilant than Americans in within-group competitions, anticipating more unethical behaviors from their peers. Study 2 replicated this finding by comparing areas within China, finding that people from China's collectivistic rice-farming regions exhibit greater ingroup vigilance than people from the less collectivistic wheat-farming regions. The rice/wheat difference was mediated by greater perceived within-group competition. Study 3 found that Chinese participants were more likely than Americans to interpret a peer's friendly behavior as sabotage in disguise. We also manipulated within-group competition and found that it increased ingroup vigilance in both cultures. Finally, study 3 identified two boundary conditions where cultural differences in ingroup vigilance decrease: an unambiguously competitive win-lose situation where Americans also exhibit vigilance, and an unambiguously cooperative win-win situation where Chinese participants relax their vigilance. This research contributes to a more balanced view of collectivism, revealing its interpersonal tensions in the forms of within-group competition and ingroup vigilance.

Relationship of resting heart rate and blood pressure with all-cause and cardiovascular disease mortality.

OBJECTIVES: This study aimed to investigate associations of resting heart rate (RHR) and blood pressure (BP) with all-cause and cardiovascular disease (CVD) mortality. STUDY DESIGN: A retrospective cohort study. METHODS: A total of 67,028 Chinese participants aged ≥60 years were included in the analysis. RHR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were evaluated according to quartiles ([41-69, 70-74, 75-79, 80-127 beats/min], [80-119, 120-129, 130-139, 140-238 mm Hg], and [40-70, 71-79, 80-84, 85-133 mm Hg]). Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and CVD mortality with RHR, SBP, and DBP. Restricted cubic splines were used to evaluate the dose-response association. RESULTS: During the 361,975 person-year follow-up, 9326 deaths were recorded, of which 5039 deaths were due to CVD. The risk of all-cause mortality was increased by 25% with the quartiles four vs quartile one of RHR (HR [95% CI]:1.25 [1.17-1.33]), and CVD mortality was increased by 32% (HR [95% CI]: 1.32 [1.22-1.44]). Similar results were observed when comparing the quartiles four vs quartile one of SBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.14 [1.07, 1.22] and 1.23 [1.12. 1.34]) and DBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.17 [1.11. 1.24] and 1.36 [1.26. 1.47]). We found linear associations of RHR, SBP, and DBP with all-cause and CVD mortality (Pnon-linearity >0.05), except for the approximately J-shaped association between DBP and all-cause mortality (Pnon-linearity = 0.008). There was a significant interaction of RHR and SBP with all-cause and CVD mortality (Pinteraction <0.05). CONCLUSIONS: RHR and BP increased the risk of all-cause and CVD mortality, especially fast RHR combined with high SBP.

[Efficacy of plasma exchange in severe crescentic IgA nephropathy: A multicentered, cohort study].

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m2), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m2) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m2)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

[Association between metabolically healthy obesity and incident risk of stroke in adult aged over 40 from rural Henan province].

Objective: To investigate the association between metabolically healthy obesity and the incident risk of stroke in people aged ≥40 years from rural areas of Henan Province. Methods: During 2007 to 2008, 20 194 residents aged ≥18 years were selected for baseline examination by random cluster sampling and 17 265 participants were followed up during 2013 to 2014. According to the aim of current study, a total of 11 864 eligible subjects were included in this post-hoc analysis. Depending on body mass index and metabolic status, subjects were divided into four groups: metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity. Multivariate logistic regression model was used to analyze the relationship between metabolically healthy obesity and the risk of stroke. Results: The median (Q1, Q3) age of study participants was 54(46, 61) years, and 4 526 participants were men. During the mean follow-up of 6 years, the cumulative incidence of stroke was 7.16%. The incidence of stroke in metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight, and metabolically abnormal obesity were 3.73%, 4.61%, 8.99% and 9.38%, respectively (χ²=117.458, P<0.001). After adjusting possible confounding factors, compared with metabolically healthy normal weight, the risk of stroke was significantly increased in the metabolically healthy obesity group, metabolically abnormal normal weight group and metabolically abnormal obesity group with the odds ratio (OR) and 95% confidence interval (CI) of 1.52(1.10-2.12), 2.11(1.61-2.77) and 2.78(2.18-3.55), respectively. Stratified analysis showed that the risk of stroke was significantly higher in metabolically healthy obesity people aged 40-59 years compared with metabolically healthy normal weight group (OR=2.12, 95%CI: 1.36-3.30). Conclusion: Metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity are positively associated with the risk of stroke.

[MRI features of lymphoepithelioma-like intrahepatic cholangiocarcinoma].

Objective: To investigate the MRI manifestations of lymphoepithelioma-like intrahep cholangiocarcinoma (LEL-ICC). Methods: MR images of 26 cases with LEL-ICC confirmed pathologically at Zhongshan Hospital Affiliated with Fudan University between March 2011 and March 2021 were retrospectively analyzed. The number, location, size, morphology, edges of lesions, non-scan signal intensity, cystic necrosis, enhancement mode, peak, and capsule, vascular invasion, lymph node metastasis, and other MR images were included for analysis. The apparent diffusion coefficient (ADC) value of the lesion and the surrounding normal liver parenchyma were measured. A paired-sample t-test was used to statistically analyze the measurement data. Results: All 26 cases of LEL-ICC had solitary lesions. Mass-type LEL-ICC was the most common [n=23, lesion size (4.02±2.32) cm] with distribution along the bile duct [n=3, lesion size (7.23±1.40 cm)]. Among the 23 lesions of mass type LEL-ICC, most of the lesions were close to the liver capsule (n=20), round (n=22), clearly bordered (n=13), and cystic necrosis (n=22). In the three lesions of LEL-ICC distributed along the bile duct, most of them were close to the liver capsule (n=2), irregular (n=3), blurred edges (n=3), and cystic necrosis (n=3). All 26 lesions showed a low/slightly low signal on T1WI, a high/slightly high signal on T2WI, and a slightly high or high signal on DWI. Three lesions showed fast-in and fast-out enhancement modes, and 23 lesions showed continuous enhancement. Twenty-five lesions showed peak enhancement in the arterial phase, and one lesion appeared in the delayed phase. The ADC value of 26 lesions and adjacent normal liver parenchyma was (1.112±0.274)×10-3 mm2/s and (1.482±0.346)×10-3 mm2/s, respectively, and the both had a statistically significant difference (P<0.05). Conclusion: Certain manifestations of LEL-ICC in magnetic resonance imaging are advantageous for diagnosis and differential diagnosis.

Thermally-assisted milling and hydrogenolysis for synthesizing ultrafine MgH2with destabilized thermodynamics.

A novel process has been developed to synthesize MgH2nanoparticles by combining ball milling and thermal hydrogenolysis of di-n-butylmagnesium (C4H9)2Mg, denoted as MgBu2. With the aid of mechanical impact, the hydrogenolysis temperature of MgBu2in heptane and cyclohexane solution was considerably lowered down to 100 °C, and the MgH2nanoparticles with an average particle size ofca.8.9 nm were obtained without scaffolds. The nano-size effect of the MgH2nanoparticles causes a notable decrease in the onset dehydrogenation temperature of 225 °C and enthalpy of 69.78 kJ mol-1 · H2. This thermally-assisted milling and hydrogenolysis process may also be extended for synthesizing other nanomaterials.

MicroRNA-20a suppresses RANKL-modulated osteoclastogenesis and prevents bone erosion in mice with rheumatoid arthritis through the TLR4/p38 pathway.

Abnormal osteoclast formation plays a significant part in rheumatoid arthritis (RA). As potent therapeutic biomarkers, microRNAs (miRNAs) have obtained increasing attention. Recently, treatment regimens regarding miRNAs have been implicated in skeletal diseases. The aim of this study is to assess the expression and function of miR-20a during osteoclast proliferation and differentiation and its correlation with bone erosion in RA mice. The expression of miR-20a was observed to be diminished in the ankle tissues of RA mice relative to that in normal controls evaluated by RT-qPCR. Hematoxylin and eosin staining, Safranin O-fast green staining, and tartrateresistant acid phosphatase staining were used to evaluate the effects of miR-20a on RA symptoms. The proliferation and differentiation of osteoclasts, and bone erosion were repressed by agomiR-20a injection. 3'UTR luciferase reporter assays were conducted to validate the putative binding between miR-20a and receptor activation of nuclear factor-κB ligand (RANKL). The protein expression and phosphorylation level of toll-like receptor4 (TLR4)/p38 pathway-related factors were detected by Western blot. miR-20a inhibited proliferation and differentiation potentials to osteoclasts partly through the TLR4/p38 pathway. The current work provides evidence that miR-20a hinders proliferation and differentiation of osteoclasts by targeting RANKL through the TLR4/p38 pathway.

Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

Evaluation of the probiotic and functional potential of Lactobacillus agilis 32 isolated from pig manure.

Escherichia coli is a symbiotic bacterium in humans and animals and an important pathogen of humans and animals. Prevention and suppression of E. coli infection is of great concern. In this study, we isolated a strain of Lactobacillus agilis 32 from pig manure and evaluated its biological characteristics, and found that its bacterial survival rate was 25% after 4 h of treatment at pH 2, and under the condition of 0·5% bile concentration, its survival rate exceeds 30%. In addition, L. agilis 32 has a cell surface hydrophobicity of 77·8%, and exhibits 67·1% auto-aggregation and 63·2% aggregation with Enterotoxigenic E. coli 10 (ETEC 10). FITC fluorescence labelling showed that the fluorescence intensity of cecum was significantly higher than that of duodenum, jejunum or colon (P < 0·05), but no significant difference from ileum. Lactobacillus agilis 32 bacterial culture and CFS showed average inhibition zone diameters of 14·2 and 15·4 mm respectively. Lactobacillus agilis 32 CFS treatment can significantly reduce the pathogenicity of ETEC 10. These results show that L. agilis 32 is an active and potential probiotic, and it has a good antibacterial effect on ETEC10, which provides basic research for probiotics to prevent and treat intestinal diarrhoea pathogen infection.

The relationship between fever rate and telework implementation as a social distancing measure against the COVID-19 pandemic in Japan.

OBJECTIVES: On March 28, the Japanese government decided on the "Basic Policies for Novel Coronavirus Disease Control" and called on the public to thoroughly implement social distancing measures (i.e., behavioral restrictions to limit the frequency and intensity of human contact), especially telework. METHODS: We used population-level questionnaire data from a social networking service (SNS), with 275,560 respondents from March 5 to April 6, to evaluate the relationship between telework implementation and the presence of a fever (body temperature higher than 37.5 °C) within 1 month as a surrogate indicator of COVID-19 infection, by occupation type and age-group. RESULTS: Among company employees, statistical significance was identified in the 15- to 29-year and 30- to 59-year age-groups, showing higher fever rates in the non-teleworker group (for the 15- to 29-year age-group, non-teleworkers: 7.64%; teleworkers: 6.45%; P = 0.02; for the 30- to 59-year age-group, non-teleworkers: 3.46%; teleworkers: 3.14%; P = 0.02). CONCLUSIONS: Telework remains a controversial topic in Japan as the government called for emergency measures. Although caution is warranted in interpreting our findings because our data are limited to the voluntary SNS users, they will be essential to push forward with more measures to promote social distancing measures in the midst of Japan's current tense political climate.

[Benzodiazepines:objective evaluation and rational use].

Benzodiazepines have been on the market for more than half a century and are widely used in clinical practice. Their use in many countries has been limited in recent decades due to drug dependence and dose tolerance in some patients. Currently, benzodiazepines are still effective in treating many mental disorders, but some patients and doctors refuse to use them for fear of drug dependence and dementia caused by long-term use. The author suggests that benzodiazepines should be objectively evaluatedand rationally used.