Associations of phthalates with accelerated aging and the mitigating role of physical activity.

Phthalates are positioned as potential risk factors for health-related diseases. However, the effects of exposure to phthalates on accelerated aging and the potential modifications of physical activity remain unclear. A total of 2317 participants containing complete study-related information from the National Health and Nutrition Examination Survey 2007-2010 were included in the current study. We used two indicators, the Klemera-Doubal method biological age acceleration (BioAgeAccel) and phenotypic age acceleration (PhenoAgeAccel), to assess the accelerated aging status of the subjects. Multiple linear regression (single pollutant models), weighted quantile sum (WQS) regression, Quantile g-computation, and Bayesian kernel machine regression (BKMR) models were utilized to explore the associations between urinary phthalate metabolites and accelerated aging. Three groups of physical activity with different intensities were used to evaluate the modifying effects on the above associations. Results indicated that most phthalate metabolites were significantly associated with BioAgeAccel and PhenoAgeAccel, with effect values (ß) ranging from 0.16 to 0.21 and 0.16-0.37, respectively. The WQS indices were positively associated with BioAgeAccel (0.33, 95% CI: 0.11, 0.54) and PhenoAgeAccel (0.50, 95% CI: 0.19, 0.82). Quantile g-computation indicated that phthalate mixtures were associated with accelerated aging, with effect values of 0.15 (95% CI: 0.02, 0.28) for BioAgeAccel and 0.39 (95% CI: 0.12, 0.67) for PhenoAgeAccel respectively. The BKMR models indicated a significant positive association between the concentrations of urinary phthalate mixtures with the two indicators. In addition, we found that most phthalate metabolites showed the strongest effects on accelerated aging in the no physical activity group and that the effects decreased gradually with increasing levels of physical activity (P < 0.05 for trend). Similar results were also observed in the mixed exposure models (WQS and Quantile g-computation). This study indicates that phthalates exposure is associated with accelerated aging, while physical activity may be a crucial barrier against phthalates exposure-related aging.

Metabolomic profiles, polygenic risk scores and risk of rheumatoid arthritis: a population-based cohort study in the UK Biobank.

OBJECTIVE: To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA). METHODS: 143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level. RESULTS: A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14). CONCLUSION: Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.

Short-term association of CO and NO2 with hospital visits for glomerulonephritis in Hefei, China: a time series study.

Objective: Recent studies suggest air pollution as an underlying factor to kidney disease. However, there is still limited knowledge about the short-term correlation between glomerulonephritis (GN) and air pollution. Thus, we aim to fill this research gap by investigating the short-term correlation between GN clinical visits and air pollution exposure. Methods: Between 2015 and 2019, daily GN visit data from two grade A tertiary hospitals in Hefei City were collected, along with corresponding air pollution and meteorological data. A generalized linear model integrated with a distributed lag nonlinear model was employed to analyze the relationship between GN visits and air pollutants. Moreover, we incorporated a dual pollutant model to account for the combined effects of multiple pollutants. Furthermore, subgroup analyses were performed to identify vulnerable populations based on gender, age, and season. Results: The association between 23,475 GN visits and air pollutants was assessed, and significant positive associations were found between CO and NO2 exposure and GN visit risk. The single-day lagged effect model for CO showed increased risks for GN visits from lag0 (RR: 1.129, 95% CI: 1.031-1.236) to lag2 (RR: 1.034, 95% CI: 1.011-1.022), with the highest risk at lag0. In contrast, NO2 displayed a more persistent impact (lag1-lag4) on GN visit risk, peaking at lag2 (RR: 1.017, 95% CI: 1.011-1.022). Within the dual-pollutant model, the significance persisted for both CO and NO2 after adjusting for each other. Subgroup analyses showed that the cumulative harm of CO was greater in the cold-season and older adult groups. Meanwhile, the female group was more vulnerable to the harmful effects of cumulative exposure to NO2. Conclusion: Our study indicated that CO and NO2 exposure can raise the risk of GN visits, and female and older adult populations exhibited greater susceptibility.

A rapid and reliable method for the determination of Lactiplantibacillus plantarum during wine fermentation based on PMA-CELL-qPCR.

Real-time monitoring of microbial dynamics during fermentation is essential for wine quality control. This study developed a method that combines the fluorescent dye propidium monoazide (PMA) with CELL-qPCR, which can distinguish between dead and live microbes for Lactiplantibacillus plantarum. This method could detect the quantity of microbes efficiently and rapidly without DNA extraction during wine fermentation. The results showed that (1) the PMA-CELL-qPCR enumeration method developed for L. plantarum was optimized for PMA treatment concentration, PMA detection sensitivity and multiple conditions of sample pretreatment in wine environment, and the optimized method can accurately quantify 104-108 CFU/mL of the target strain (L. plantarum) in multiple matrices; (2) when the concentration of dead bacteria in the system is 104 times higher than the concentration of live bacteria, there is an error of 0.5-1 lg CFU/mL in the detection results. The optimized sample pretreatment method in wine can effectively reduce the inhibitory components in the qPCR reaction system; (3) the optimized PMA-CELL-qPCR method was used to monitor the dynamic changes of L. plantarum during the fermentation of Cabernet Sauvignon wine, and the results were consistent with the plate counting method. In conclusion, the live bacteria quantification method developed in this study for PMA-CELL-qPCR in L. plantarum wines is accurate in quantification and simple in operation, and can be used as a means to accurately monitor microbial dynamics in wine and other fruit wines.

N6-methyladenosine-modified circIRF2, identified by YTHDF2, suppresses liver fibrosis via facilitating FOXO3 nuclear translocation.

Circular RNA (circRNA) has been implicated in liver fibrosis and modulated by multiple elusive molecular mechanisms, while the effects of N6-methyladenosine (m6A) modification on circRNA are still elusive. Herein, we identify circIRF2 from our circRNA sequencing data, which decreased in liver fibrogenesis stage and restored in resolution stage, indicating that dysregulated circIRF2 may be closely associated with liver fibrosis. Gain/loss-of-function analysis was performed to evaluate the effects of circIRF2 on liver fibrosis at both the fibrogenesis and resolution in vivo. Ectopic expression of circIRF2 attenuated liver fibrogenesis and HSCs activation at the fibrogenesis stage, whereas downregulation of circIRF2 impaired mouse liver injury repair and inflammation resolution. Mechanistically, YTHDF2 recognized m6A-modified circIRF2 and diminished circIRF2 stability, partly accounting for the decreased circIRF2 in liver fibrosis. Microarray was applied to investigate miRNAs regulated by circIRF2, our data elucidate cytoplasmic circIRF2 may directly harbor miR-29b-1-5p and competitively relieve its inhibitory effect on FOXO3, inducing FOXO3 nuclear translocation and accumulation. Clinically, circIRF2 downregulation was prevalent in liver fibrosis patients compared with healthy individuals. In summary, our findings offer a novel insight into m6A modification-mediated regulation of circRNA and suggest that circIRF2 may be an exploitable prognostic marker and/or therapeutic target for liver fibrosis.

Global Chronic obstructive pulmonary disease burden attributable to air pollution from 1990 to 2019.

BACKGROUND: The disease burden attributable to chronic obstructive pulmonary disease (COPD) is significant worldwide. Some studies have linked exposure to air pollution to COPD, but there has been little research on this. METHODS: We aimed to assess the COPD-related disease burden attributable to air pollution from multiple epidemiological perspectives. This study conducted a three-stage analysis. Firstly, we reported on the burden of disease worldwide in 2019 by different subgroups including sex, age, region, and country. Secondly, we studied the trends in disease burden from 1990 to 2019. Finally, we explored the association of some national indicators with disease burden to look for risk factors. RESULTS: In 2019, the death number of COPD associated with air pollution accounted for 2.32% of the total global death, and the number of DALY accounted for 1.12% of the global DALY. From 1990 to 2019, the death number of COPD associated with air pollution increased peaked at 1.41 million in 1993, fluctuated, and then declined. We found the same temporal pattern of DALY. The corresponding age-standardized rates had been falling. At the same time, the burden of COPD associated with air pollution was also affected by some national indicators. CONCLUSIONS: This study indicated that air pollution-related COPD contributed to a significant global disease burden. We called for health policymakers to take action and interventions targeting vulnerable countries and susceptible populations.

Identification of the key odor-active compounds responsible for varietal smoky aroma in wines made from the East Asian species.

A smoky aroma was found in wines made from East Asian species that had not been treated with oak products or exposed to smoke. In this study, a combined method of sensory analysis and quantitation of aroma compounds was used to identify the chemical basis of this smoky aroma. Syringol, eugenol, 4-ethylguaiacol, and 4-ethylphenol were confirmed as the key odor-active compounds contributing to the varietal smoky notes in wines of East Asian species. The concentrations of these compounds showed significant variation between grape species. The highest levels of syringol were found in Vitis amurensis wines, with an average of 178.8 µg/L. The average concentration of eugenol in V. davidii wines was 101.5 µg/L, about 10 times higher than in other species. 4-Ethylphenol and 4-ethylguaiacol were both abundant in the wines of the East Asian species. The results of the sensory interaction between the four compounds showed a complete addition effect for eugenol, a partial addition effect for syringol, and a hyper-addition effect for 4-ethylguaiacol and 4-ethylphenol on the smoky attribute.

Metabolic Signature of Healthy Lifestyle and Risk of Rheumatoid Arthritis: Observational and Mendelian Randomization Study.

BACKGROUND: Although substantial evidence reveals that healthy lifestyle behaviors are associated with a lower risk of rheumatoid arthritis (RA), the underlying metabolic mechanisms remain unclear. OBJECTIVES: This study aimed to identify the metabolic signature reflecting a healthy lifestyle and investigate its observational and genetic linkage with RA risk. METHODS: This study included 87,258 UK Biobank participants (557 cases with incident RA) aged 37-73 y with complete lifestyle, genotyping, and nuclear magnetic resonance (NMR) metabolomics data. A healthy lifestyle was assessed based on 5 factors: healthy diet, regular exercise, not smoking, moderate alcohol consumption, and normal body mass index. The metabolic signature was developed by summing the selected metabolites' concentrations weighted by the coefficients using elastic net regression. We used the multivariate Cox model to assess the associations between metabolic signatures and RA risk, and examined the mediating role of the metabolic signature in the impact of a healthy lifestyle on RA. We performed genome-wide association analysis (GWAS) to obtain genetic variants associated with the metabolic signature and then conducted Mendelian randomization (MR) analyses to detect causality. RESULTS: The metabolic signature comprised 81 metabolites, robustly correlated with a healthy lifestyle (r = 0.45, P = 4.2 × 10-15). The metabolic signature was inversely associated with RA risk (HR per standard deviation (SD) increment: 0.76; 95% CI: 0.70-0.83), and largely explained the protective effects of healthy lifestyle on RA with 64% (95% CI: 50.4-83.3) mediation proportion. 1- and 2-sample MR analyses also consistently showed the associations of genetically inferred per SD increment in metabolic signature with a reduction in RA risk (HR: 0.84; 95% CI: 0.75-0.94; and P = 0.002 and OR: 0.84; 95% CI: 0.73-0.97; and P = 0.02, respectively). CONCLUSIONS: Our findings implicate that the metabolic signature reflecting healthy lifestyle is a potential causal mediator in the development of RA, highlighting the importance of early lifestyle intervention and metabolic status tracking for precise prevention of RA.

RIPK2 as a promising druggable target for autoimmune diseases.

Receptor Interacting Serine/Threonine Kinase 2 (RIPK2) is an essential regulator of the inflammatory process and immune response. In innate immunity, the NOD-RIPK2 signaling axis is an important pathway that directly mediates inflammation and immune response. In adaptive immunity, RIPK2 may affect T cell proliferation, differentiation and cellular homeostasis thereby involving T cell-driven autoimmunity, but the exact mechanism remains unclear. Recent advances suggest a key role of RIPK2 in diverse autoimmune diseases (ADs) such as inflammatory bowel diseases, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and Behcet's disease. This review aims to provide valuable therapeutic direction for ADs by focusing on the function and modulation of RIPK2 in innate and adaptive immunity, its involvement with various ADs and the application of RIPK2-related drugs in ADs. We raise the notion that drug targeting RIPK2 could be a promising therapeutic strategy for the treatment of ADs, though much work remains to be done for clinical application.

A Case of Giant Perianal Condylomata Acuminata with IgA Nephropathy Treated Successfully by a Topical Chinese Medicine Preparation Paiteling.

Giant condylomata acuminata (a sexually transmitted disease caused by HPV infection) currently is treated in many methods. Surgery, the mainstay treatment of giant condylomata acuminata, may cause a high cost or scar formation. It is important to explore effective and safe treatment options. Although the external treatment of traditional Chinese medicine treatment of condyloma acuminatum has not been widely used, in our case, the use of traditional Chinese medicine successfully treated a perianal giant condyloma acuminatum patient who also suffered from mixed hemorrhoid and IgA nephropathy meanwhile. The treatment process was simple and the effect obvious. There was no recurrence more than 10 months after treatment finished, and the patients felt safe, comfortable and highly coordinated. The outcome of this case suggests that the traditional Chinese medicine might be considered as a mild and effective option for the treatment of giant condyloma acuminatum.

Association of Combined Exposure to Ambient Air Pollutants, Genetic Risk, and Incident Rheumatoid Arthritis: A Prospective Cohort Study in the UK Biobank.

BACKGROUND: Evidence for a potential link between air pollution and rheumatoid arthritis (RA) is inconsistent, and the modified effect of genetic susceptibility on the relationship between air pollution and RA has not been well studied. OBJECTIVE: Using a general population cohort from the UK Biobank, this study aimed to investigate the associations between various air pollutants and the risk of incident RA and to further estimate the impact of combined exposure to ambient air pollutants on the risk of developing RA under the modification effect of genetic predisposition. METHODS: A total of 342,973 participants with completed genotyping data and who were free of RA at baseline were included in the study. An air pollution score was constructed by summing the concentrations of each pollutant weighted by the regression coefficients with RA from single-pollutant models to assess the combined effect of air pollutants, including particulate matter (PM) with diameters ≤2.5µm (PM2.5), between 2.5 and 10µm (PM2.5-10), and ≤10µm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). In addition, the polygenic risk score (PRS) of RA was calculated to characterize individual genetic risk. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of associations of single air pollutant, air pollution score, or PRS with incident RA. RESULTS: During a median follow-up time of 8.1 y, 2,034 incident events of RA were recorded. The HRs (95% CIs) of incident RA per interquartile range increment in PM2.5, PM2.5-10, PM10, NO2, and NOx were 1.07 (1.01, 1.13), 1.00 (0.96, 1.04), 1.01 (0.96, 1.07), 1.03 (0.98, 1.09), and 1.07 (1.02, 1.12), respectively. We also found a positive exposure-response relationship between air pollution score and RA risk (pTrend=0.000053). The HR (95% CI) of incident RA was 1.14 (1.00, 1.29) in the highest quartile group compared with the lowest quartile group of the air pollution score. Furthermore, the results of the combined effect of air pollution score and PRS on the RA risk showed that the risk of RA incidence in the highest genetic risk and air pollution score group was almost twice that of the lowest genetic risk and air pollution score group [incidence rate (IR) per 100,000 person-years: 98.46 vs. 51.19, and HR= 1.73 (95% CI: 1.39, 2.17) vs. 1 (reference)], although no statistically significant interaction between the air pollution and genetic risk for incident RA was found (pInteraction>0.05). DISCUSSION: The results revealed that long-term combined exposure to ambient air pollutants might increase the risk of RA, particularly in those with high genetic risk. https://doi.org/10.1289/EHP10710.

Association between Meteorological Factors and Outpatient Visits for Herpes Zoster in Hefei, China: A Time-Series Analysis.

This study sought to investigate the relationship between meteorological factors and outpatient visits for herpes zoster. In this time-series analysis, we used data from two major hospitals in Hefei, collected between 2015 and 2019, to evaluate the impact of meteorological factors on the risk of herpes zoster. After controlling for confounders, we adopted a distributed lag nonlinear model to probe the relationship between meteorological factors and outpatient visits for herpes zoster. The analysis was stratified according to age (<40 years, ≥40 years) and sex (male, female). A total of 43,547 cases of herpes zoster were reported, and compared with the median value, a high temperature and high relative humidity had a significant risk effect on the incidence of herpes zoster. The maximum harmful effect of high temperature on herpes zoster occurred on the lag0 (RR: 1.027, 95% CI: 1.002-1.053) and further declined over the following days. The cumulative effect increased with the extension of lag days, and the cumulative RR was the largest on the sixth day of lag (RR1.031, 95% CI: 1.006-1.056) when the relative humidity was 85.7% (77.0% as the reference). The stratified analysis results reveal that females and the elderly (≥40 years) were more susceptible to temperature and relative humidity. This study shows that high-temperatures may lead to herpes zoster, indicating that those infected with varicella zoster virus need to take measures over the course of several days when not exposed to the best appropriate temperature conditions.

Increased circulating sclerostin levels in rheumatoid arthritis patients: an updated meta-analysis.

BACKGROUND: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/ß-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role. METHOD: PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA). RESULTS: Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P < 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients. CONCLUSION: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.

Short-term effect of ambient temperature and ambient temperature changes on the risk of warts outpatient visits in Hefei, China: a retrospective time-series study.

Concerns are growing about the adverse health effects of ambient temperature and ambient temperature changes. However, the association between ambient temperature and ambient temperature changes on the risk of warts outpatient visits is poorly understood. Our study used the distributed lag non-linear model (DLNM) aimed to evaluate the association between ambient temperature, ambient temperature changes (including temperature change between neighboring days (TCN) and diurnal temperature range (DTR)), and warts outpatient visits. We also performed subgroup analyses in order to find susceptible populations by gender and age groups. The maximum relative risk (RR) of low ambient temperature (0 °C) for warts outpatient visits was 1.117 (95% CI: 1.041-1.198, lag 04 days), and the maximum RR of high ambient temperature (32 °C) for warts outpatient visits was 1.318 (95% CI: 1.083-1.605, lag 07 days). The large temperature drop (TCN = - 3 °C) decreased the risk of warts visits, with the lowest RR value at the cumulative exposure of lag 7 days (RR = 0.888, 95% CI: 0.822-0.959), and the large temperature rise (TCN = 2 °C) increased the risk of warts visits, with the highest RR value at the cumulative exposure of lag 7 days (RR = 1.080, 95% CI: 1.022-1.142). Overall, both low and high ambient temperatures and large temperature rise can increase the risk of warts visits, while large temperature drop is a protective factor for warts visits. However, we did not find any association between DTR and warts visits. Furthermore, subgroup analyses showed that males and the young (0-17 years old) were more sensitive to low and high ambient temperatures, and the elderly (≥ 65 years old) were more susceptible to TCN. The results may provide valuable evidence for reducing the disease burden of warts in the future.

Iron Competition as an Important Mechanism of Pulcherrimin-Producing Metschnikowia sp. Strains for Controlling Postharvest Fungal Decays on Citrus Fruit.

This study identified and tested fruit-isolated Metschnikowia yeasts against three major postharvest citrus pathogens, namely, Penicillium digitatum, Penicillium italicum, and Geotrichum citri-aurantii, and further evaluated the impact of FeCl3 on the biocontrol efficiency of pulcherrimin-producing M. pulcherrima strains. Based on the characterization of the pigmented halo surrounding the colonies and the analysis of the D1/D2 domain of 26S rDNA, a total of 46 Metschnikowia sp. were screened and identified. All 46 Metschnikowia strains significantly inhibited the hyphal growth of Penicillium digitatum, Penicillium italicum, and Geotrichum citri-aurantii, and effectively controlled the development of green mold, blue mold and sour rot of citrus fruit. The introduction of exogenous FeCl3 at certain concentrations did not significantly impact the pulcherriminic acid (PA) production of pigmented M. pulcherrima strains, but notably diminished the size of pigmented zones and the biocontrol efficacy against the three pathogens. Iron deficiency sensitivity experiments revealed that P. digitatum and P. italicum exhibited higher sensitivity compared to G. citri-aurantii, indicating that iron dependence varied among the three pathogens. These results suggested that M. pulcherrima strains, capable of producing high yields of PA, possessed great potential for use as biocontrol agents against postharvest citrus diseases. The biocontrol efficacy of these yeasts is mainly attributed to their ability to competitively deplete iron ions in a shared environment, with the magnitude of their pigmented halo directly correlating to their antagonistic capability. It is worth noting that the level of sensitivity of pathogens to iron deficiency might also affect the biocontrol effect of pulcherrimin-producing M. pulcherrima.

Effect of low temperature on the shaping of yeast-derived metabolite compositions during wine fermentation.

Low-temperature fermentation is considered to enrich the aroma of wine. The metabolism of Saccharomyces cerevisiae responding to low temperatures is intricate and this complexity is further enhanced by various strains and culture media. However, the real effects of low-temperature fermentation on yeast metabolism are unclear. Aiming to clarify the yeast-derived metabolite formation in a low-temperature winemaking range, fermentations were performed at 10, 15, and 20 °C, using five wine yeast strains in two media respectively. Tolerance toward low temperatures and metabolite compositions (including basic chemical compositions and volatile aroma compounds) of wine yeasts were analyzed. Results showed that ethanol, ethyl acetate, and ethyl butanoate increased with the temperature decreasing, while acetic acid, phenylethanol, phenylethyl acetate, ethyl decanoate, and ethyl hexadecanoate decreased with decreasing temperature. The linear relationship between fermentation temperature and the formation of ethanol, acetic acid, and phenylethanol might be fundamentally due to the growth changes caused by temperature. The enhanced production of ethyl acetate and ethyl butyrate followed by decreasing temperature probably resulted from low-temperature-stimulated enzymes in metabolic pathways. These findings reveal a typical profile of yeast-derived metabolites at low-temperature fermentation and provide evidence to support the application of low-temperature winemaking in the wine industry.

Altered gut fungi in systemic lupus erythematosus - A pilot study.

Objective: Gut fungi, as symbiosis with the human gastrointestinal tract, may regulate physiology via multiple interactions with host cells. The plausible role of fungi in systemic lupus erythematosus (SLE) is far from clear and need to be explored. Methods: A total of 64 subjects were recruited, including SLE, rheumatoid arthritis (RA), undifferentiated connective tissue diseases (UCTDs) patients and healthy controls (HCs). Fecal samples of subjects were collected. Gut fungi and bacteria were detected by ITS sequencing and 16S rRNA gene sequencing, respectively. Alpha and beta diversities of microbiota were analyzed. Linear discriminant analysis effect size analysis was performed to identify abundance of microbiota in different groups. The correlation network between bacterial and fungal microbiota was analyzed based on Spearman correlation. Results: Gut fungal diversity and community composition exhibited significant shifts in SLE compared with UCTDs, RA and HCs. Compared with HCs, the alpha and beta diversities of fungal microbiota decreased in SLE patients. According to principal coordinates analysis results, the constitution of fungal microbiota from SLE, RA, UCTDs patients and HCs exhibited distinct differences with a clear separation between fungal microbiota. There was dysbiosis in the compositions of fungal and bacterial microbiota in the SLE patients, compared to HCs. Pezizales, Cantharellales and Pseudaleuria were enriched in SLE compared with HCs, RA and UCTDs. There was a complex relationship network between bacterial and fungal microbiota, especially Candida which was related to a variety of bacteria. Conclusion: This study presents a pilot analysis of fungal microbiota with diversity and composition in SLE, and identifies several gut fungi with different abundance patterns taxa among SLE, RA, UCTDs and HCs. Furthermore, the gut bacterial-fungal association network in SLE patients was altered compared with HCs.

Accuracy of Ultrasound Diagnosis of Thyroid Nodules Based on Artificial Intelligence-Assisted Diagnostic Technology: A Systematic Review and Meta-Analysis.

Background: Ultrasonography (US) is the most common method of identifying thyroid nodules, but US images require an experienced surgeon for identification. Many artificial intelligence (AI) techniques such as computer-aided diagnostic systems (CAD), deep learning (DL), and machine learning (ML) have been used to assist in the diagnosis of thyroid nodules, but whether AI techniques can improve the diagnostic accuracy of thyroid nodules still needs to be explored. Objective: To clarify the accuracy of AI-based thyroid nodule US images for differentiating benign and malignant thyroid nodules. Methods: A search strategy of "subject terms + key words" was used to search PubMed, Cochrane Library, Embase, Web of Science, China Biology Medicine (CBM), and China National Knowledge Infrastructure (CNKI) for studies on AI-assisted diagnosis of thyroid nodules based on US images. The summarized receiver operating characteristic (SROC) curve and the pooled sensitivity and specificity were used to assess the performance of the diagnostic tests. The quality assessment of diagnostics accuracy studies-2 (QUADAS-2) tool was used to assess the methodological quality of the included studies. The Review Manager 5.3 and Stata 15 were used to process the data. Subgroup analysis was based on the integrity of data collection. Results: A total of 25 studies with 17,429 US images of thyroid nodules were included. AI-assisted diagnostic techniques had better diagnostic efficacy in the diagnosis of benign and malignant thyroid nodules: sensitivity 0.88 (95% CI: (0.85-0.90)), specificity 0.81 (95% CI: 0.74-0.86), diagnostic odds ratio (DOR) 30 (95% CI: 19-46). The SROC curve indicated that the area under the curve (AUC) was 0.92 (95% CI: 0.89-0.94). Threshold effect analysis showed a Spearman correlation coefficient: 0.17 < 0.5, suggesting no threshold effect for the included studies. After a meta-regression analysis of 4 different subgroups, the results showed a statistically significant effect of mean age ≥50 years on heterogeneity. Compared with studies with an average age of ≥50 years, AI-assisted diagnostic techniques had higher diagnostic performance in studies with an average age of <50 years (0.89 (95% CI: 0.87-0.92) vs. 0.80 (95% CI: 0.73-0.88)), (0.83 (95% CI: 0.77-0.88) vs. 0.73 (95% CI: 0.60-0.87)). Conclusions: AI-assisted diagnostic techniques had good diagnostic efficacy for thyroid nodules. For the diagnosis of <50 year olds, AI-assisted diagnostic technology was more effective in diagnosis.

Pilot-Scale Vinification of Cabernet Sauvignon Using Combined Lactiplantibacillus plantarum and Saccharomyces cerevisiae to Achieve Wine Acidification.

Insufficient acidity in grape berries from warm climate regions has been exacerbated due to global warming, thereby becoming a major concern for winemaking. The wine lactic acid bacterium Lactiplantibacillus plantarum has potential to ameliorate wine acidity by producing lactic acid from hexose metabolism, but its impact on wine compositions and sensory outcomes is not well studied. Here, we evaluated acidification and fermentation performance of indigenous L. plantarum in two inoculation regimes (i.e., reverse inoculation and co-inoculation) by conducting pilot-scale vinification using Cabernet Sauvignon with low acidity. Important parameters of the bio-acidified wines, including fermentation kinetics, basic oenological parameters, volatile and sensory profile were compared to those in wines produced by single Saccharomyces cerevisiae with/without chemical acidification. Total titratable acidity in L. plantarum wines were either comparable or significantly higher compared to the chemical acidification control. Chemical profiling reviewed remarkable differences in certain organic acids and major volatile compounds, especially an up to a five-fold, six-fold, and nine-fold increase in lactic acid, ethyl lactate and isoamyl lactate, respectively. Changes in chemical compositions of the bio-acidified wines resulted in differentiated sensory perception compared to the control wines. Except having higher scores for "wine acidity", the flavour profile of the bio-acidified wines was shifted towards "jammy fruit" and "butter" aromas. Together, these findings highlighted the applicability of using L. plantarum to induce biological acidification along with modulation of wine flavour.

The Interaction Between Dietary Fructose and Gut Microbiota in Hyperuricemia and Gout.

With the worldwide epidemics of hyperuricemia and associated gout, the diseases with purine metabolic disorders have become a serious threat to human public health. Accumulating evidence has shown that they have been linked to increased consumption of fructose in humans, we hereby made a timely review on the roles of fructose intake and the gut microbiota in regulating purine metabolism, together with the potential mechanisms by which excessive fructose intake contributes to hyperuricemia and gout. To this end, we focus on the understanding of the interaction between a fructose-rich diet and the gut microbiota in hyperuricemia and gout to seek for safe, cheap, and side-effect-free clinical interventions. Furthermore, fructose intake recommendations for hyperuricemia and gout patients, as well as the variety of probiotics and prebiotics with uric acid-lowering effects targeting the intestinal tract are also summarized to provide reference and guidance for the further research.