Potassium affects the association between dietary intake of vitamin C and NAFLD among adults in the United States.

INTRODUCTION: Although the association between nonalcoholic fatty liver disease (NAFLD) and vitamin C has been well studied, the effects of dietary potassium intake on this relationship are still unclear. Thus, this study aimed to determine the effects of dietary potassium intake on the association between vitamin C and NAFLD. METHODS: We performed a cross-sectional learn about with 9443 contributors the usage of 2007-2018 NHANES data. Multiple logistic regression evaluation has been utilized to check out the affiliation of dietary vitamin C intake with NAFLD and advanced hepatic fibrosis (AHF). Subsequently, we plotted a smoothed match curve to visualize the association. Especially, the analysis of AHF was conducted among the NAFLD population. In addition, stratified evaluation used to be developed primarily based on demographic variables to verify the steadiness of the results. Effect amendment by way of dietary potassium intake used to be assessed via interplay checks between vitamin C and NAFLD in the multivariable linear regression. RESULTS: In this cross-sectional study, we found that vitamin C was negatively related to NAFLD and AHF. The relationship between vitamin C and NAFLD was different in the low, middle and high potassium intake groups. Furthermore, potassium intake significantly modified the negative relationship between vitamin C and NAFLD in most of the models. CONCLUSION: Our research showed that potassium and vitamin C have an interactive effect in reducing NAFLD, which may have great importance for clinical medication.

Bone morphogenetic protein 10 and atrial fibrillation.

Background: The association between bone morphogenetic protein 10 (BMP10) and atrial fibrillation (AF) has been widely investigated by observational studies, but their causal relationships remain inconclusive. Here, we aimed to evaluate the causal effect of BMP10 on the risk of AF through single-nucleotide polymorphisms. Methods: A Mendelian randomization (MR) analytic framework was applied to data from two BMP10-specific genome-wide association studies comprising a total of 11,036,163 single-nucleotide polymorphisms of European ancestry. Instrument genetic variants associated with BMP10 were selected. A total of 12 AF-specific genome-wide association studies comprising a total of 5,095,117 European participants were included. Summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were used. Pleiotropy and sensitivity were assessed. Results: Specific to AF-specific genome-wide association studies, we found that BMP10 was not associated with AF among different methods (all P > 0.05). We further identified no significant horizontal pleiotropy (all P > 0.05) and no fundamental impact among various data. Conclusions: This large-scale population study upon data from BMP10- and AF-specific genome-wide association studies and a longitudinal biobank cohort indicates plausible non-causal associations between BMP10 and AF in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.

FASN Inhibition Decreases MHC-I Degradation and Synergizes with PD-L1 Checkpoint Blockade in Hepatocellular Carcinoma.

Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Mechanistically, FASN inhibition reduced palmitoylation of MHC-I that led to its lysosomal degradation. The palmitoyltransferase DHHC3 directly bound MHC-I and negatively regulated MHC-I protein levels. In an orthotopic HCC mouse model, Fasn deficiency enhanced MHC-I levels and promoted cancer cell killing by tumor-infiltrating CD8+ T cells. Moreover, the combination of two different FASN inhibitors, orlistat and TVB-2640, with anti-PD-L1 antibody robustly suppressed tumor growth in vivo. Multiplex IHC of human HCC samples and bioinformatic analysis of The Cancer Genome Atlas data further illustrated that lower expression of FASN was correlated with a higher percentage of cytotoxic CD8+ T cells. The identification of FASN as a negative regulator of MHC-I provides the rationale for combining FASN inhibitors and immunotherapy for treating HCC. SIGNIFICANCE: Inhibition of FASN increases MHC-I protein levels by suppressing its palmitoylation and lysosomal degradation, which stimulates immune activity against hepatocellular carcinoma and enhances the efficacy of immune checkpoint inhibition.

Global, regional, and national time trends in incidence for tuberculosis, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease 2019 study.

BACKGROUND: Tuberculosis (TB) represents a significant global health concern, being the leading cause of mortality from a single infectious agent worldwide. The investigation of TB incidence and epidemiological trends is critical for evaluating the effectiveness of control strategies and identifying ongoing challenges. OBJECTIVES: This study presents the trend in TB incidence across 204 countries and regions over a 30-year period. METHODS: The study utilises data sourced from the Global Burden of Disease (GBD) database. The age cohort model and gender subgroup analysis were employed to estimate the net drift (overall annual percentage change), local drift (age annual percentage change), longitudinal age curve (expected age ratio), and cycle and cohort effect (relative risk of cycle and birth cohort) of TB incidence from 1990 to 2019. This approach facilitates the examination and differentiation of age, period, and cohort effects in TB incidence trends, potentially identifying disparities in TB prevention across different countries. RESULTS: Over the past three decades, a general downward trend in TB incidence has been observed in most countries. However, in 15 of the 204 countries, the overall incidence rate is still on the rise (net drift ≥0.0 %) or stagnant decline (≥-0.5 %). From 1990 to 2019, the net drift of tuberculosis mortality ranged from -2.2 % [95 % confidence interval (CI): -2.33, -2.05] in high Socio-demographic Index (SDI) countries to -1.7 % [95 % CI: -1.81, -1.62] in low SDI countries. In some below-average SDI countries,men in the birth cohort are at a disadvantage and at risk of deterioration, necessitating comprehensive TB prevention and treatment. CONCLUSIONS: While the global incidence of TB has declined, adverse period and cohort effects have been identified in numerous countries, raising questions about the adequacy of TB healthcare provision across all age groups. Furthermore, this study reveals gender disparities in TB incidence.

Genetic Contributions to Attachment Stability Over Time: the Roles of CRHR1 Polymorphisms.

Corticotropin-releasing hormone receptor 1 (CRHR1), a hormone receptor essential to the activation of HPA axis and the subsequent release of cortisol, plays critical roles in emotional and behavioral responses relevant to attachment. However, the specific roles of CRHR1 polymorphisms in attachment remain unclear. To further clarify these genetic effects, this research conducted a three-wave study to investigate whether the CRHR1 polymorphisms (i.e., rs110402 and rs242924) are associated with the stability and variability of attachment by using a sample of freshmen (N = 604; Mage = 18.57 years, SD = 1.90; 68.8% girls). The results showed that rs110402 and rs242924 were associated with the stability of closeness-dependence. The G alleles of the both polymorphisms were found not to be related to lower attachment stability. However, these polymorphisms were not associated with the variability of attachment. Overall, these findings provide evidence for the contribution of CRHR1 to attachment stability.

Deep learning-based 3D brain multimodal medical image registration.

Medical image registration is a critical preprocessing step in medical image analysis. While traditional medical image registration techniques have matured, their registration speed and accuracy still fall short of clinical requirements. In this paper, we propose an improved VoxelMorph network incorporating ResNet modules and CBAM (RCV-Net), for 3D multimodal unsupervised registration. Unlike popular convolution-based U-shaped registration networks like VoxelMorph, RCV-Net incorporates the convolutional block attention module (CBAM) during the convolution process. This inclusion enhances the feature map information extraction capabilities during training and effectively prevents information loss. Additionally, we introduce a lightweight and residual network module at the network's base, which enhances learning ability without significantly increasing training parameters. To evaluate the superiority of our registration model, we utilize evaluation metrics such as structural similarity (SSIM), peak signal-to-noise ratio (PSNR), and mean square error (MSE). Experimental results demonstrate that our proposed network structure outperforms current state-of-the-art methods, yielding better performance in multimodal registration tasks. Furthermore, generalization testing on databases outside of the training set has confirmed the optimal registration effectiveness of our model.

Action mechanism of the potential biocontrol agent Brevibacillus laterosporus SN19-1 against Xanthomonas oryzae pv. oryzae causing rice bacterial leaf blight.

The causal agent of rice bacterial leaf blight (BLB) is Xanthomonas oryzae pv. oryzae (Xoo), which causes serious damage to rice, leading to yield reduction or even crop failure. Brevibacillus laterosporus SN19-1 is a biocontrol strain obtained by long-term screening in our laboratory, which has a good antagonistic effect on a variety of plant pathogenic bacteria. In this study, we investigated the efficacy and bacterial inhibition of B. laterosporus SN19-1 against BLB to lay the theoretical foundation and research technology for the development of SN19-1 as a biopesticide of BLB. It was found that SN19-1 has the ability to fix nitrogen, detoxify organic phosphorus, and produce cellulase, protease, and siderophores, as well as IAA. In a greenhouse pot experiment, the control efficiency of SN19-1 against BLB was as high as 90.92%. Further investigation of the inhibitory mechanism of SN19-1 on Xoo found that the biofilm formation ability of Xoo was inhibited and the pathogenicity was weakened after the action of SN19-1 sterile supernatant on Xoo. The activities of enzymes related to respiration and the energy metabolism of Xoo were significantly inhibited, while the level of intracellular reactive oxygen species was greatly increased. Scanning electron microscopy observations showed folds on the surface of Xoo. A significant increase in cell membrane permeability and outer membrane permeability and a decrease in cell membrane fluidity resulted in the extravasation of intracellular substances and cell death. The results of this study highlight the role of B. laterosporus SN19-1 against the pathogen of BLB and help elucidate the underlying molecular mechanisms.

Identifying the Interaction Between Tuberculosis and SARS-CoV-2 Infections via Bioinformatics Analysis and Machine Learning.

The number of patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 is still increasing. In the case of COVID-19 and tuberculosis (TB), the presence of one disease affects the infectious status of the other. Meanwhile, coinfection may result in complications that make treatment more difficult. However, the molecular mechanisms underpinning the interaction between TB and COVID-19 are unclear. Accordingly, transcriptome analysis was used to detect the shared pathways and molecular biomarkers in TB and COVID-19, allowing us to determine the complex relationship between COVID-19 and TB. Two RNA-seq datasets (GSE114192 and GSE163151) from the Gene Expression Omnibus were used to find concerted differentially expressed genes (DEGs) between TB and COVID-19 to identify the common pathogenic mechanisms. A total of 124 common DEGs were detected and used to find shared pathways and drug targets. Several enterprising bioinformatics tools were applied to perform pathway analysis, enrichment analysis and networks analysis. Protein-protein interaction analysis and machine learning was used to identify hub genes (GAS6, OAS3 and PDCD1LG2) and datasets GSE171110, GSE54992 and GSE79362 were used for verification. The mechanism of protein-drug interactions may have reference value in the treatment of coinfection of COVID-19 and TB.

UBR4 deficiency causes male sterility and testis abnormal in Drosophila.

Introduction: It has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model. Methods: Different Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila. Results: We found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility. Discussion: Overall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression.

Immunological effects of recombinant Lactobacillus casei expressing pilin MshB fused with cholera toxin B subunit adjuvant as an oral vaccine against Aeromonas veronii infection in crucian carp.

Aeromonas veronii is a zoonotic agent capable of infecting fish and mammals, including humans, posing a serious threat to the development of aquaculture and public health safety. Currently, few effective vaccines are available through convenient routes against A. veronii infection. Herein, we developed vaccine candidates by inserting MSH type VI pili B (MshB) from A. veronii as an antigen and cholera toxin B subunit (CTB) as a molecular adjuvant into Lactobacillus casei and evaluated their immunological effect as vaccines in a crucian carp (Carassius auratus) model. The results suggested that recombinant L. casei Lc-pPG-MshB and Lc-pPG-MshB-CTB can be stably inherited for more than 50 generations. Oral administration of recombinant L. casei vaccine candidates stimulated the production of high levels of serum-specific immunoglobulin M (IgM) and increased the activity of acid phosphatase (ACP), alkaline phosphatase (AKP) superoxide dismutase (SOD), lysozyme (LZM), complement 3 (C3) and C4 in crucian carp compared to the control group (Lc-pPG612 group and PBS group) without significant changes. Moreover, the expression levels of interleukin-10 (IL-10), interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß) genes in the gills, liver, spleen, kidney and gut of crucian carp orally immunized with recombinant L. casei were significantly upregulated compared to the control groups, indicating that recombinant L. casei induced a significant cellular immune response. In addition, viable recombinant L. casei can be detected and stably colonized in the intestine tract of crucian carp. Particularly, crucian carp immunized orally with Lc-pPG-MshB and Lc-pPG-MshB-CTB exhibited higher survival rates (48% for Lc-pPG-MshB and 60% for Lc-pPG-MshB-CTB) and significantly reduced loads of A. veronii in the major immune organs after A. veronii challenge. Our findings indicated that both recombinant L. casei strains provide favorable immune protection, with Lc-pPG-MshB-CTB in particular being more effective and promising as an ideal candidate for oral vaccination.

Machine learning algorithm to construct cuproptosis- and immune-related prognosis prediction model for colon cancer.

BACKGROUND: Over the past few years, research into the pathogenesis of colon cancer has progressed rapidly, and cuproptosis is an emerging mode of cellular apoptosis. Exploring the relationship between colon cancer and cuproptosis benefits in identifying novel biomarkers and even improving the outcome of the disease. AIM: To look at the prognostic relationship between colon cancer and the genes associated with cuproptosis and the immune system in patients. The main purpose was to assess whether reasonable induction of these biomarkers reduces mortality among patients with colon cancers. METHOD: Data obtained from The Cancer Genome Atlas and Gene Expression Omnibus and the Genotype-Tissue Expression were used in differential analysis to explore differential expression genes associated with cuproptosis and immune activation. The least absolute shrinkage and selection operator and Cox regression algorithm was applied to build a cuproptosis- and immune-related combination model, and the model was utilized for principal component analysis and survival analysis to observe the survival and prognosis of the patients. A series of statistically meaningful transcriptional analysis results demonstrated an intrinsic relationship between cuproptosis and the micro-environment of colon cancer. RESULTS: Once prognostic characteristics were obtained, the CDKN2A and DLAT genes related to cuproptosis were strongly linked to colon cancer: The first was a risk factor, whereas the second was a protective factor. The finding of the validation analysis showed that the comprehensive model associated with cuproptosis and immunity was statistically significant. Within the component expressions, the expressions of HSPA1A, CDKN2A, and UCN3 differed markedly. Transcription analysis primarily reflects the differential activation of related immune cells and pathways. Furthermore, genes linked to immune checkpoint inhibitors were expressed differently between the subgroups, which may reveal the mechanism of worse prognosis and the different sensitivities of chemotherapy. CONCLUSION: The prognosis of the high-risk group evaluated in the combined model was poorer, and cuproptosis was highly correlated with the prognosis of colon cancer. It is possible that we may be able to improve patients' prognosis by regulating the gene expression to intervene the risk score.

Primulalizipingensis (Primulaceae), a new species from Sichuan, China.

A new species, Primulalizipingensis W.B.Ju, L.Y.He & X.F.Gao, found in Shimian County, Sichuan, China, is described and illustrated. It is morphologically similar to P.rhodochroa and P.socialis, but can be distinguished from them in having shorter plants covering with white farinose, leaf margin sharply dentate above the middle, the leaf blade becomes papery after drying, scapes obsolete, the bract linear-lanceolate to subulate, solitary at the base of the pedicel, and the white hairs present inside the corolla tube.

Systematic evaluation of line probe assays for the diagnosis of tuberculosis and drug-resistant tuberculosis.

BACKGROUND: Line probe assays (LPAs) are PCR-based assays used for the rapid diagnosis of Mycobacterium tuberculosis (MTB) and drug-resistant tuberculosis (DR-TB). But studies on its performance are insufficient. Thus, in this study, we conducted a systematic review and meta-analysis to evaluate the effect of LPAs in the detection of MTB and drug-resistant TB in comparison with the traditional culture and DST methods. METHODS: A systemic literature search was conducted on the Web of Science, Embase, PubMed, the Cochrane Library, Scopus, and OVID databases. All the included studies were classified according to different detecting objects. Sensitivity, specificity, Positive Likely Ratio (PLR), Negative Likely Ratio (NLR), Diagnostic Odds Ratio (DOR), corresponding 95% confidence interval, Area Under Curve (AUC), Deeks' funnel plot, and Bivariate Boxplot was used to do the evaluation. RESULTS: 147 studies included 491 datasets, with 182,448 samples, were incorporated into our analysis. The sensitivity (95% CI), specificity (95% CI), PLR, NLR, DOR and AUC for MTB were 0.89 (0.86 to 0.92), 0.94 (0.90 to 0.97), 15.70, 0.11, 139 and 0.96, respectively; for rifampicin-resistant TB were 0.96 (0.95 to 0.97), 0.99 (0.98 to 0.99), 82.9, 0.04, 1994 and 1.00, respectively; for isoniazid-resistant TB were 0.91 (0.89 to 0.93), 0.99 (0.98 to 0.99), 83.4, 0.09, (0.99 to 1.00), 195.7, 0.07, 2783 and 1.00, respectively; for Multi-drug resistant TB (MDR-TB) were 0.93 (0.90 to 0.95), 1.00 (0.99 to 1.00), 195.7, 0.07, 2783 and 1.00, respectively; for extensively drug-resistant TB (XDR-TB) were 0.60 (0.33 to 0.82), 1.00 (0.95 to 1.00), 291.3, 0.4, 726 and 0.95, respectively; for (second-line drug-resistant TB) SLID-TB were 0.83 (0.78 to 0.87), 0.98 (0.97 to 0.99), 44.6, 0.17, 262 and 0.98, respectively. Sensitivity in pre-extensively drug-resistant TB (Pre-XDR-TB) was 0.67, specificity was 0.91. No publication bias existed according to Deeks' funnel plot. CONCLUSION: High diagnosis performance was confirmed in LPAs for the diagnosis of MTB and drug-resistant TB. LPAs might be a good alternative to culture and DST in detecting MTB, RR-TB, INH-TB, XDR-TB, SLID-TB, and MDR-TB. While more studies were still needed to explore the diagnosis performance of LPAs for Pre-XDR TB.

Evaluation of GeneXpert EV assay for the rapid diagnosis of enteroviral meningitis: a systematic review and meta-analysis.

BACKGROUND: GeneXpert enterovirus Assay is a PCR-based assay for Enterovirus meningitis diagnosis. However, there is currently no research about the performance of GeneXpert enterovirus assay in the diagnosis of enterovirus meningitis. Thus, a systematic review and meta-analysis is significant on the topic. METHODS: Embase, Cochrane Library, Web of Science, and PubMed were systematically reviewed with retrieval types. Some criteria were used to filter the studies. Only studies published in English, that made a comparison between GeneXpert enterovirus assay and RT-PCR, and could be formulated in a 2*2 table, were included. The quality of the included studies was evaluated by QUADAS-2. The effect of the GeneXpert enterovirus assay was assessed by the Sensitivity, Specificity, Positive Likelihood Ratio, Negative Likelihood Ratio, Diagnosis Odds Ratio, and summary receiver operating characteristic (SROC) curve. Publication bias and heterogeneity were evaluated by the Deeks' funnel test and Bivariate Box plot respectively. RESULTS: 7 studies were recruited in the analysis. The Pooled Sensitivity was 0.96 [95% CI (0.94-0.97)], Pooled Specificity was 0.99 [95% CI (0.98-0.99)], Positive Likelihood Ratio was 130.46 [95% CI (35.79-475.58)], Negative Likelihood Ratio was 0.04 [95% CI (0.02-0.10)], and Diagnostic Odds Ratio was 3648.23 (95% CI [963.99-13,806.72)]. In SROC Curve, Area Under Curve (AUC) was 0.9980, and Q*= 0.9849. In Deeks' funnel test, the P-value was 0.807 (P > 0.05), indicating no publication bias. The Bivariate Box plot indicated no evident heterogeneity. CONCLUSIONS: The GeneXpert enterovirus assay demonstrated high diagnostic accuracy in diagnosing enterovirus meningitis.

A modularized high-power ultra-wideband radiation system based on the space-synthesis method.

In this paper, a high-power ultra-wideband radiation system, composed of multiply radiation modules, is developed based on the space-synthesis method. The radiation module mainly consists of a transistorized pulser, a 2 × 2 combined antenna array, and a power divider. To improve the out parameters [the amplitude, the pulse repetition frequency (PRF), and the rise time] of the transistorized pulser based on the Marx circuit, the influence of the traveling wave process on the output pulse must be concerned. Based on the theoretical analysis, the printed circuit board circuit parameters and the circuit structure of the pulser are optimized. To improve the power synthesis efficiency, the pulse jitter characteristic of the pulser is improved by replacing the conventional base triggering mode with the collector voltage ramp triggering mode for the first-stage avalanche transistor in the pulser. The previous optimized antenna array is utilized in this radiation system, which has a better radiation performance in the prescribed aperture area. In addition, based on the gradient microstrip structure, the power divider integrated with the pulser is designed, which has the advantages of wide bandwidth, low loss, and light weight. Experimental results show that the peak effective potential rEp of the radiation system of 20 radiation modules is 221.8 kV, the maximum PRF could reach 10 kHz, and the half-power radiation angles of its radiation field are about 5° in both the E plane and the H plane. More radiation modules could be integrated into the system to achieve a higher electric field in the future.

Simultaneous Detection of Multiple Plant Growth Regulator Residues in Cabbage and Grape Using an Optimal QuEChERS Sample Preparation and UHPLC-MS/MS Method.

BACKGROUND: At present, plant growth regulators (PGRs) are widely used in agricultural and forestry production. PGRs, like traditional pesticides, have certain toxicities. Naively excessively applying them will cause the acute and chronic poisoning of humans and animals and potentially harm human health. OBJECTIVE: In order to assess, prevent, and control the residues of PGRs in fruits and vegetables, a set of quick, easy, cheap, effective, rugged, and safe (QuEChERS) analytical methods that simultaneously detect multiple PGR residues are urgently needed for quality and safety inspection of agricultural product. METHODS: In this study, grapes (representative of fruits) and cabbages (representative of vegetables) were used as the detected objects. The 30 commercial product residues of PGRs were detected in both with an ultra-high performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS/MS) method, based on optimized chromatographic, MS, and preparation conditions (extraction solvent and cleanup conditions). Grape and cabbage samples were extracted with acetonitrile containing 5% (v/v) acetic acid, dehydrated using a salt package, purified using the QuEChERS method, ionized using electrospray ionization under positive and negative ion switching mode, detected using multi-reaction monitoring, and quantification using an external standard method of matrix matching standard curve. RESULTS: Methanol was selected as the strong elution phase. A methanol-0.1% formic acid-5 mmol/L ammonium acetate solution was selected as the best mobile phase. The optimal extraction solvent was acetonitrile containing 5% acetic acid. Primary secondary amine cleanup could met the determination requirements of PGR residues. The developed method for determination of 30 commercial products of PGR, such as betaine, showed excellent linearity in 1-500, 10-1000, ∼500, ∼2000, and 100-10 000 µg/kg (R ≥ 0.98). At the 0.001 (0.01), 0.05, 0.20, and 1.00 mg/kg additive concentrations, the average addition standard recovery of 30 commercial products of PGR were 61-132% with the relative standard deviations of 1-14% and the LOQs were confirmed to be 1.0-100 µg/kg through the actual addition values of samples. CONCLUSION: The set of optimized QuEChERS UHPLC-MS/MS methods simultaneously detect residues of PGRs in fruits and vegetables with one-time sample preparation for high-throughput, rapid quantitative screening, and confirmation. The methods cover a wide range of PGRs with simple and convenient preparation and small amounts of solvent, and can provide technical support for the supervision of PGR residues in fruits and vegetables. HIGHLIGHTS: The optimizations of extraction solvent screening, different ratios of various purification packages in the QuEChERS method, and UPLC-MS conditions were conducted and the precision, sensitivity, and recovery rates of the methods were investigated in order to establish a QuEChERS UPLC-MS/MS method for simultaneously detecting 30 kinds of PGR residues in fruits and vegetables. The methods allow high-throughput determination of multiple PGR residues in fruits and vegetables and can also provide technical references for related compound residue detection of other matrixes.

Transcriptomic analysis of the ΔPaLoc mutant of Clostridioides difficile and verification of its toxicity / 中华预防医学杂志

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.

Serum vitamin E levels and chronic inflammatory skin diseases: A systematic review and meta-analysis.

BACKGROUND: Vitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases. METHODS: We searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected. RESULTS: Twenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30). CONCLUSIONS: Our meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases.

Transcriptome sequencing and metabolome analysis reveal the mechanism of Shuanghua Baihe Tablet in the treatment of oral mucositis.

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg-1·d-1. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues. After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.

Soluble microbial products from the white-rot fungus Phanerochaete chrysosporium as the bioflocculant for municipal wastewater treatment.

Soluble microbial products (SMP), a type of polymers released from microbial metabolism and decay, show great potential for wastewater treatment as bioflocculants; however, biogenic flocculant utilization is currently limited to bacterial SMP. In this study, SMP produced by Phanerochaete chrysosporium BKMF-1767 (SMP-P) was investigated to determine the application potential of fungal SMP. SMP-P exhibited high flocculation activity in kaolin suspension at a dosage range of 0.67-0.84 mg/L with Ca2+ assistance, comparable to that of commercial polyacrylamide. The high molecular weight polysaccharides (2.0 × 106-4.7 × 107 Da) in SMP-P, which enabled flocculation via the bridging mechanism and served as the dominant active constituent, were composed of glucose and arabinose at a molar ratio of 1: 0.03, with (1 â†’ 4, 6)-linked glucose as the main backbone and a small proportion of branched structures. They contained hydroxyl and carboxyl, effective functional groups for the flocculation process, and displayed parallel self-orientation behavior in water. Efficient chemical oxygen demand removal was achieved during municipal wastewater treatment using SMP-P as the bioflocculant. This study demonstrates the feasibility of utilizing fugal SMP as bioflocculants and provides guidance for their practical application.