High throughput identification of carbonyl compounds in natural organic matter by directional derivatization combined with ultra-high resolution mass spectrometry.

Carbonyl compounds are important components of natural organic matter (NOM) with high reactivity, so that play a pivotal role in the dynamic transformation of NOM. However, due to the lack of effective analytical methods, our understanding on the molecular composition of these carbonyl compounds is still limited. Here, we developed a high-throughput screening method to detect carbonyl molecules in complex NOM samples by combining chemical derivatization with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS). In six different types of dissolved organic matter (DOM) samples tested in this study, 20-30 % of detected molecules contained at least one carbonyl group, with relative abundance accounted for 45-70 %. These carbonyl molecules displayed lower unsaturation level, lower molecular weight, and higher oxidation degree compared to non-carbonyl molecules. More importantly, the measured abundances of carbonyl molecules were consistent with the results of 13C nuclear magnetic resonance (NMR) analysis. Based on this method, we found that carbonyl molecules can be produced at DOM-ferrihydrite interface, thus playing a role in shaping the molecular diversity of DOM. This method has broad application prospects in screening carbonyl compounds from complex mixtures, and the same strategy can be used to directional identification of molecules with other functional groups as well.

The effect of acupuncture on lateral habenular nucleus and intestinal microflora in depression model rats.

BACKGROUND: Depression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats. RESULTS: The results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents. CONCLUSION: Acupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.

Acupuncture exerts preventive effects in rats of chronic unpredictable mild stress: The involvement of inflammation in amygdala and brain-spleen axis.

BACKGROUND: Acupuncture has shown the preventive effects on depression in rats with chronic unpredictable mild stress (CUMS). However, the mechanisms of acupuncture for preventing depression still need to be explored. In the study, acupuncture was applied to a rat depression model of CUMS, high-mobility group box 1(HMGB1)/toll-like receptor 4 (TLR4) and brain-spleen axis were assessed. METHODS: Male Sprague Dawley (SD) rats were exposed to CUMS with two stressors per day for 28 days. In the meantime, manual acupuncture (at GV16 and GV23 acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL) were administered daily post CUMS stressors. Behavioral tests and biological detection methods were conducted in sequence to evaluate depression-like phenotypes in rats. RESULTS: The results showed CUMS induced depression-like behaviors, hyper-activation of HMGB1/TLR4 signaling pathway, elevated inflammation in amygdala and peripheral blood, and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis. These changes could be prevented and reversed by acupuncture to varying extents. CONCLUSION: Acupuncture prevented and ameliorated depression-like symptoms induced by CUMS, possibly via regulating inflammation through brain-spleen axis mediated by HMGB1/TLR4 signaling pathway and HPA axis regulation.

Development and validation of short-term renal prognosis prediction model in diabetic patients with acute kidney injury.

OBJECTIVE: Diabetes is a major cause of the progression of acute kidney injury (AKI). Few prediction models have been developed to predict the renal prognosis in diabetic patients with AKI so far. The aim of this study was to develop and validate a predictive model to identify high-risk individuals with non-recovery of renal function at 90 days in diabetic patients with AKI. METHODS: Demographic data and related laboratory indicators of diabetic patients with AKI in the First Affiliated Hospital of Guangxi Medical University from January 31, 2012 to January 31, 2022 were retrospectively analysed, and patients were followed up to 90 days after AKI diagnosis. Based on the results of Logistic regression, a model predicting the risk of non-recovery of renal function at 90 days in diabetic patients with AKI was developed and internal validated. Consistency index (C-index), calibration curve, and decision curve analysis were used to evaluate the differentiation, accuracy, and clinical utility of the prediction model, respectively. RESULTS: A total of 916 diabetic patients with AKI were enrolled, with a male to female ratio of 2.14:1. The rate of non-recovery of renal function at 90 days was 66.8% (612/916). There were 641 in development cohort and 275 in validation cohort (ration of 7:3). In the development cohort, a prediction model was developed based on the results of Logistic regression analysis. The variables included in the model were: diabetes duration (OR = 1.022, 95% CI 1.012-1.032), hypertension (OR = 1.574, 95% CI 1.043-2.377), chronic kidney disease (OR = 2.241, 95% CI 1.399-3.591), platelet (OR = 0.997, 95% CI 0.995-1.000), 25-hydroxyvitamin D3 (OR = 0.966, 95% CI 0.956-0.976), postprandial blood glucose (OR = 1.104, 95% CI 1.032-1.181), discharged serum creatinine (OR = 1.003, 95% CI 1.001-1.005). The C-indices of the prediction model were 0.807 (95% CI 0.738-0.875) and 0.803 (95% CI 0.713-0.893) in the development and validation cohorts, respectively. The calibration curves were all close to the straight line with slope 1. The decision curve analysis showed that in a wide range of threshold probabilities. CONCLUSION: A prediction model was developed to help predict short-term renal prognosis of diabetic patients with AKI, which has been verified to have good differentiation, calibration degree and clinical practicability.

Influence of Red Blood Cell Distribution Width on All-Cause Death in Critical Diabetic Patients with Acute Kidney Injury.

Objective: To explore the relationship between red blood cell distribution width (RDW) and all-cause death in critical diabetic patients with acute kidney injury (AKI). Methods: The clinical data of critical diabetic patients with AKI in MIMIC-III database were analyzed retrospectively. According to the survival status of 28-day after AKI and levels of RDW, patients were divided into survival and death groups, high RDW (RDW > 15.3%) and low RDW groups (RDW ≤ 15.3%). Kaplan-Meier curves were used to compare the survival rates of diabetic patients with AKI in different RDW and AKI stages, and Cox regression analysis was used to evaluate the risk factors of 28-day all-cause death in critical diabetic patients with AKI. Results: A total of 5200 patients with critical diabetic patients with AKI were included in this study with the male to female ratio of 1.53:1. The mean follow-up time was 24.97 ± 7.14 days, and the 28-day all-cause mortality was 17.9% (931/5200). Age, RDW, blood urea nitrogen, serum creatinine, lactic acid, proportion of AKI stage, sepsis and respiratory failure in the death group were higher than those in the survival group, while mean arterial pressure (MAP) and red blood cell count were lower than those in the survival group. Kaplan-Meier analysis showed that the 28-day survival rate of the high RDW group was significantly lower than that of the low RDW group (log-rank χ 2 = 9.970, P = 0.002). Multivariate Cox regression analysis showed that advanced age (HR = 1.042, 95% CI = 1.021-1.063), decreased MAP (HR = 0.984, 95% CI = 0.969-0.998), stage 3 AKI (HR = 3.318, 95% CI = 1.598-6.890) and increased RDW (HR = 1.255, 95% CI = 1.123-1.403) were independent risk factors of 28-day all-cause death in critical diabetic patients with AKI (P < 0.05). Conclusion: High level of RDW is an important risk factor of all-cause death in critical diabetic patients with AKI, and it may be used as a valuable index to classify the mortality.

Relationship between total testosterone, sex hormone-binding globulin levels and the severity of non-alcoholic fatty liver disease in males: a meta-analysis.

Background: In recent years, many studies have reported the relationship between non-alcoholic fatty liver disease (NAFLD) and sex hormones, especially total testosterone (TT) and sex hormone-binding globulin (SHBG). However, the relationship between sex hormones and the severity of NAFLD is still unclear. Methods: PubMed, Embase, Cochrane Library, Web of Science, WanFang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to 31 August 2021. Values of weighted mean differences (WMDs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined by Stata 12.0 software to evaluate the relationship between TT, SHBG and the severity of NAFLD in males. Results: A total of 2995 patients with NAFLD from 10 published cross-sectional studies were included for further analysis. The meta-analysis indicated that the moderate-severe group had a lower TT than the mild group in males with NAFLD (WMD: -0.35 ng/ml, 95% CI = -0.50 to -0.20). TT and SHBG were important risk factors of moderate-severe NAFLD in males (ORTT = 0.79, 95% CI = 0.73 to 0.86; ORSHBG = 0.22, 95% CI = 0.12 to 0.39; p < 0.001). Moreover, when the analysis was limited to men older than age 50, SHBG levels were lower in those with moderate-severe disease (WMD: -11.32 nmol/l, 95% CI = -14.23 to -8.40); while for men with body mass index (BMI) >27 kg/m2, moderate-severe NAFLD had higher SHBG levels than those with mild disease (WMD: 1.20 nmol/l, 95% CI = -2.01 to 4.42). Conclusion: The present meta-analysis shows that lower TT is associated with the severity of NAFLD in males, while the relationship between SHBG and severity of NAFLD is still to be further verified.

The safety and efficacy evaluation of sodium-glucose co-transporter 2 inhibitors for patients with non-alcoholic fatty liver disease: An updated meta-analysis.

BACKGROUND: In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been increasingly used in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). This updated meta-analysis aimed to evaluate the efficacy and safety of SGLT2is for patients with NAFLD. METHODS: PubMed, Embase, Cochrane Library, Web of Science, Wan Fang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to April 30, 2021. Values of weighted mean differences (WMDs) and risk ratios (RRs) were determined for continuous and dichotomous outcomes, respectively. RESULTS: A total of 1,498 patients with NAFLD from 20 studies were included for further analysis. Pooled analyses indicated significant improvements in body mass index [WMD: -0.84 kg/m2, 95% CI (-1.09, -0.60)], alanine aminotransferase [WMD: -4.36 U/L, 95% CI (-7.17, -1.54)], aspartate aminotransferase [WMD: -2.94 U/L, 95% CI (-5.33, -0.55)], fasting plasma glucose [WMD: -4.08 mmol/L, 95% CI (-6.21, -1.95)] and fibrosis-4 index [WMD: -0.08, 95% CI (-0.11, -0.05)] following SGLT2i treatment (p < 0.01 for all above parameters). There was no significant difference in the incidence of total adverse events between the SGLT2i group and the control group (RR = 0.78, 95% CI (0.58, 1.06), p = 0.11]. CONCLUSION: SGLT2is seem to be a promising treatment for patients with NAFLD to improve metabolic and fibrosis indexes without increasing the incidence of adverse events. Most included studies were conducted in NAFLD patients with diabetes. Therefore, the results of this meta-analysis are more applicable to the diabetic population.

Polychlorinated dibenzo-p-dioxins and dibenzofurans in lotus from a lake historically polluted by the chlor-alkali industry: Occurrence, organ distribution and health risk from dietary intake.

In this study, the organ distribution and exposure risk from dietary intake of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were investigated for lotus collected from Ya-er Lake, a lake in Hubei Province, Central China that was historically polluted by the chlor-alkali industry. The highest concentrations of PCDD/Fs were found in the main and fibrous lotus roots, with mean values of 48.9 ± 90.1 pg/g and 94.6 ± 143 pg/g, respectively. In all the investigated samples, Octa-CDD (OCDD) and Octa-CDF (OCDF) were the predominant congeners, at 26% and 17% of Σ17 PCDD/Fs, respectively, followed by 1,2,3,4,6,7,8-HpCDF (9%). The distribution ratios of PCDD/Fs in adjacent lotus organs indicated that PCDD/Fs accumulated easily in edible organs, such as lotus seeds, membrane and leaves. The WHO-TEQ in the edible lotus organs and the probable daily intake (PDI) of lotus products by residents were calculated: the toxic equivalents in the lotus fruit parts reached a mean of 2 pg WHO-TEQ2005/g dw, and the mean weekly intake of lotus products for adolescents living around Ya-er Lake was 2.3 pg WHO-TEQ/kg bw/week. These results suggested that long-term consumption of lotus products from Ya-er Lake presents a health hazard to residents.

Perfluorooctane sulfonate (PFOS) disturbs fatty acid metabolism in Caenorhabditis elegans: Evidence from chemical analysis and molecular mechanism exploration.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that might induce disorders in fatty acid (FA) metabolism, but the underlying mechanisms remain unresolved. Caenorhabditis elegans (C. elegans) as a model organism can synthesize polyunsaturated FAs de novo via the polyunsaturated FA synthesis pathway. In this study, synchronized L1 C. elegans were exposed to 0, 0.01, 0.1, 0.5 and 1 µM PFOS for 72 h. Gas chromatography-mass spectrometry (GC-MS) was used to establish a sensitive and reliable analysis method for PFASs in exposed nematode, the instrument detection limits of nine fatty acid methyl esters examined ranged between 1.11 and 27.6 ng/mL, with satisfactory reproducibility (RSD < 10%) observed. Methyl pentadecanoate (C15:0) was used as an internal standard, the linearity of the calibration (0.1-10 µg/mL) nine FAs from the nematode were quantitatively analyzed. Comparing with the control group, PFOS exposure caused significantly decreased levels of C18:0 while significantly increased levels of C18:3n6. A decrease in the C18:3n6: C18:2n6 ratio was observed. Consistently, expression of the FA desaturation gene fat-3 was significantly down-regulated. These findings suggest that the FA disorder is associated with decrease in mRNA expression of Δ6-desaturase genes in C. elegans. Simultaneously, the disorders in FA metabolism were found to disrupt mitochondrial function with a reduction in ATP synthesis, as determined by the luciferase method. In summary, the results of the study provide insights into the adverse effects of PFOS on FA metabolism in living organisms.

Cyclic Phenylmethylsiloxane Oligomers in Municipal Landfills and Their Elimination Mechanisms in Leachate Treatment Processes.

This study investigated some sources and elimination mechanisms of phenylmethylsiloxanes in landfill leachates. During a 20-day leaching experiment for electronic wastes collected from one Chinese landfill, significant release (4.9 ng/L to 1.3 µg/L) of cis-/trans-2,4,6-triphenyl-2,4,6-trimethylcyclotrisiloxanes (cis-P3 and trans-P3) and cis-/trans-2,4,6,8-tetraphenyl-2,4,6,8-tetramethylcyclotetrasiloxanes (cis-P4 and trans-P4a,b,c) in simulated leachates was found. From January 2017 to December 2018, P3 and P4 isomers were detected in raw leachates from active cells [

Development and Validation of a Prediction Model for Survival in Diabetic Patients With Acute Kidney Injury.

Objective: We aimed to analyze the risk factors affecting all-cause mortality in diabetic patients with acute kidney injury (AKI) and to develop and validate a nomogram for predicting the 90-day survival rate of patients. Methods: Clinical data of diabetic patients with AKI who were diagnosed at The First Affiliated Hospital of Guangxi Medical University from April 30, 2011, to April 30, 2021, were collected. A total of 1,042 patients were randomly divided into a development cohort and a validation cohort at a ratio of 7:3. The primary study endpoint was all-cause death within 90 days of AKI diagnosis. Clinical parameters and demographic characteristics were analyzed using Cox regression to develop a prediction model for survival in diabetic patients with AKI, and a nomogram was then constructed. The concordance index (C-index), receiver operating characteristic curve, and calibration plot were used to evaluate the prediction model. Results: The development cohort enrolled 730 patients with a median follow-up time of 87 (40-98) days, and 86 patients (11.8%) died during follow-up. The 90-day survival rate was 88.2% (644/730), and the recovery rate for renal function in survivors was 32.9% (212/644). Multivariate analysis showed that advanced age (HR = 1.064, 95% CI = 1.043-1.085), lower pulse pressure (HR = 0.964, 95% CI = 0.951-0.977), stage 3 AKI (HR = 4.803, 95% CI = 1.678-13.750), lower 25-hydroxyvitamin D3 (HR = 0.944, 95% CI = 0.930-0.960), and multiple organ dysfunction syndrome (HR = 2.056, 95% CI = 1.287-3.286) were independent risk factors affecting the all-cause death of diabetic patients with AKI (all p < 0.01). The C-indices of the prediction cohort and the validation cohort were 0.880 (95% CI = 0.839-0.921) and 0.798 (95% CI = 0.720-0.876), respectively. The calibration plot of the model showed excellent consistency between the prediction probability and the actual probability. Conclusion: We developed a new prediction model that has been internally verified to have good discrimination, calibration, and clinical value for predicting the 90-day survival rate of diabetic patients with AKI.

Quercetin regulates fibrogenic responses of endometrial stromal cell by upregulating miR-145 and inhibiting the TGF-ß1/Smad2/Smad3 pathway.

OBJECTIVES: Aim of this study is to explore whether quercetin can inhibit the enlarged fibrogenic responses of endometrial stromal cells by increasing the level of microRNA-145 (miR-145) and mediating the TGFß1/Smad2/Smad3 signaling pathway, and to discuss the mechanism of signal transduction, further to provide experimental basis for revealing the pathophysiological mechanism and seeking new strategies for effective prevention and treatment of endometrial fibrosis. METHODS: The expression levels of miR-145 and TGF-ß receptor 2 (TGFBR2) were detected by RT-qPCR analysis. Expressions of α-smooth muscle actin (α-SMA) and vimentin were examined by immunofluorescence staining. Cell viability was measured by MTT assay. The protein expression of collagen type 1 alpha 1 (Col1a1), α-SMA, fibronectin (FN), TGFBR2, transforming growth factor (TGF-ß1), Smad2/3, phospho-Smad2/3 (p-Smad2/3) were detected by western blot analysis. The interaction between miR-145 and TGFBR2 was confirmed by dual-luciferase reporter gene assay. RESULTS: The expression level of miR-145 was decreased, whereas TGFBR2 was increased in intrauterine adhesion tissue. The expression levels of COL1A1, α-SMA, FN, TGFBR2, and p-Smad2/3 were increased, whereas miR-145 and cell proliferation were decreased in human endometrial stromal cells (hESCs) in response to TGF-ß1 stimulation in a time and dose-dependent manner, which could be reversed by quercetin. Furthermore, quercetin regulates cell fibrogenic responses of endometrial stromal cells via miR-145/TGF-ß1/Smad2/Smad3 pathway. CONCLUSIONS: These findings indicated that quercetin have a significant anti-fibrotic effect and could upregulate miR-145 and inhibit activation of TGF-ß1/Smad2/Smad3 pathway to regulate TGF-ß1 induced fibrogenic responses of endometrial stromal cells, which may serve as a potential therapeutic agent for endometrial fibrosis.

Phenylmethylsiloxanes and trifluoropropylmethylsiloxanes in municipal sludges from wastewater treatment plants in China: Their distribution, degradation and risk assessment.

Based on wastewater and raw/digested sludge samples from 29 wastewater treatment plants in 25 Chinese cities, the nationwide profiles of cis- and trans- isomers of phenylmethylsiloxanes (P3 and P4) and trifluoropropylmethylsiloxanes (D3F and D4F) were investigated. Calculated with paired influents/sludges positive for these compounds, majority (93% at mean) of them were found accumulating in raw sludges [

Methylsiloxanes and Their Brominated Products in One e-Waste Recycling Area in China: Emission, Environmental Distribution, and Elimination.

The present study investigated the sources and fates of methylsiloxanes and their brominated products in one e-waste recycling area of China. During thermal (30-1000 °C) recycling experiments for printed wiring boards (PWBs), besides volatile methylsiloxanes (D4, D5, and D6), their monobrominated products, that is, D3D(CH2Br), D4D(CH2Br), and D5D(CH2Br), were also found by quadrupole time-of-flight gas chromatography-mass spectrometry to have 2-3 orders of magnitude lower emissions (0.31-1.3 µg/g) than those (18.1-866 µg/g) of parent methylsiloxanes. Overall, the fastest emissions of methylsiloxanes and bromo-methylsiloxanes occurred at 300-400 and 400-500 °C, respectively, accounting for 35.3-51.0 and 39.4-82.1% of their total emission. In the e-waste recycling area, concentrations of D4-D6 were 1.1-75.0 µg/g dw [detection frequency (df) = 100%] in 31 dusts from PWB treatment workshops, while limits of detection (LOD) < 683 ng/g dw (df = 69-100%) in 48 surrounding soils were up to 3 orders of magnitudes higher than those in reference areas. Meanwhile, D3D(CH2Br)-D5D(CH2Br) were detected in both dusts (

Continuous citric acid production in repeated-fed batch fermentation by Aspergillus niger immobilized on a new porous foam.

The efficiency of current methods for industrial production of citric acid is limited. To achieve continuous citric acid production with enhanced yield and reduced cost, immobilized fermentation was employed in an Aspergillus niger 831 repeated fed-batch fermentation system. We developed a new type of material (PAF201), which was used as a carrier for the novel adsorption immobilization system. Hydrophobicity, pore size and concentration of carriers were researched in A. niger immobilization. The efficiency of the A. niger immobilization process was analyzed by scanning electron microscopy. Then eight-cycle repeated fed-batch cultures for citric acid production were carried out over 600 h, which showed stable production with maximum citric acid concentrations and productivity levels of 162.7 g/L and 2.26 g L-1 h-1, respectively. Compared with some other literatures about citric acid yield, PAF201 immobilization system is 11.3% higher than previous results. These results indicated that use of the new adsorption immobilization system could greatly improve citric acid productivity in repeated fed-batch fermentation. Moreover, these results could provide a guideline for A.niger or other filamentous fungi immobilization in industry.