Characteristic profiling of soluble factors in the cerebrospinal fluid of patients with neurosyphilis.

BACKGROUND: Soluble inflammatory factors have been investigated in the cerebrospinal fluid (CSF) of neurosyphilis patients with low-throughput technology. This study aimed to illustrate the characteristics of soluble factors profiles in CSF of neurosyphilis patients. METHODS: We measured the concentrations of 45 cytokines/chemokines/growth factors in CSF from 112 untreated syphilis cases, including latent syphilis (LS), asymptomatic neurosyphilis (ANS), meningeal neurosyphilis (MNS), meningovascular neurosyphilis (MVNS), paralytic dementia (PD) and ocular syphilis (OS). RESULTS: Thirty-three differentially expressed soluble factors (DeSFs) were categorized into three clusters. DeSFs scores of cluster 1 and 2 (DeSFS1 and DeSFS2) were positively correlated with elevated neopterin and neurofilament light subunit (NF-L) concentration, respectively. DeSFs scores of cluster 3 were positively correlated with WBC, protein, NF-L and neopterin. Patients with LS, ANS, and OS exhibited an overall lower abundance of DeSFs. PD patients exhibited significantly increased levels of cluster 1 and 3, and the highest total DeSFs score, while patients with MNS and MVNS showed enhanced levels of cluster 2. ROC analysis revealed that DeSFS1 effectively discriminated PD, and DeSFS2 discriminated MNS/MVNS with high accuracy. CONCLUSIONS: Patients with neurosyphilis at different stages have distinctive patterns of soluble factors in CSF, which are correlated with immune status and neuronal damage.

Comparative phylogenetic analysis of the mediator complex subunit in asparagus bean (Vigna unguiculata ssp. sesquipedialis) and its expression profile under cold stress.

BACKGROUND: The mediator complex subunits (MED) constitutes a multiprotein complex, with each subunit intricately involved in crucial aspects of plant growth, development, and responses to stress. Nevertheless, scant reports pertain to the VunMED gene within the context of asparagus bean (Vigna unguiculata ssp. sesquipedialis). Establishing the identification and exploring the responsiveness of VunMED to cold stress forms a robust foundation for the cultivation of cold-tolerant asparagus bean cultivars. RESULTS: Within this study, a comprehensive genome-wide identification of VunMED genes was executed in the asparagus bean cultivar 'Ningjiang3', resulting in the discovery of 36 distinct VunMED genes. A phylogenetic analysis encompassing 232 MED genes from diverse species, including Arabidopsis, tomatoes, soybeans, mung beans, cowpeas, and asparagus beans, underscored the highly conserved nature of MED gene sequences. Throughout evolutionary processes, each VunMED gene underwent purification and neutral selection, with the exception of VunMED19a. Notably, VunMED9/10b/12/13/17/23 exhibited structural variations discernible across four cowpea species. Divergent patterns of temporal and spatial expression were evident among VunMED genes, with a prominent role attributed to most genes during early fruit development. Additionally, an analysis of promoter cis-acting elements was performed, followed by qRT-PCR assessments on roots, stems, and leaves to gauge relative expression after exposure to cold stress and subsequent recovery. Both treatments induced transcriptional alterations in VunMED genes, with particularly pronounced effects observed in root-based genes following cold stress. Elucidating the interrelationships between subunits involved a preliminary understanding facilitated by correlation and principal component analyses. CONCLUSIONS: This study elucidates the pivotal contribution of VunMED genes to the growth, development, and response to cold stress in asparagus beans. Furthermore, it offers a valuable point of reference regarding the individual roles of MED subunits.

GMOIT: a tool for effective screening of genetically modified crops.

BACKGROUND: Advancement in agricultural biotechnology has resulted in increasing numbers of commercial varieties of genetically modified (GM) crops worldwide. Though several databases on GM crops are available, these databases generally focus on collecting and providing information on transgenic crops rather than on screening strategies. To overcome this, we constructed a novel tool named, Genetically Modified Organisms Identification Tool (GMOIT), designed to integrate basic and genetic information on genetic modification events and detection methods. RESULTS: At present, data for each element from 118 independent genetic modification events in soybean, maize, canola, and rice were included in the database. Particularly, GMOIT allows users to customize assay ranges and thus obtain the corresponding optimized screening strategies using common elements or specific locations as the detection targets with high flexibility. Using the 118 genetic modification events currently included in GMOIT as the range and algorithm selection results, a "6 + 4" protocol (six exogenous elements and four endogenous reference genes as the detection targets) covering 108 events for the four crops was established. Plasmids pGMOIT-1 and pGMOIT-2 were constructed as positive controls or calibrators in qualitative and quantitative transgene detection. CONCLUSIONS: Our study provides a simple, practical tool for selecting, detecting, and screening strategies for a sustainable and efficient application of genetic modification.

Elevated liver enzymes in the first trimester are associated with gestational diabetes mellitus: A prospective cohort study.

AIMS: Previous studies have found that a single liver enzyme may predict gestational diabetes mellitus (GDM), but the results have been inconsistent. This study aimed to explore the associations of liver enzymes in early pregnancy with risk of GDM, as well as to independently rank risk factors. METHODS: This prospective cohort study included 1295 women who underwent liver enzyme measurements during early pregnancy and completed GDM assessment in mid-pregnancy. Logistic regression and restricted cubic spline analyses were conducted to assess the relationship between liver enzymes and risk of GDM. Back-propagation artificial neural network was performed to rank independently risk factors of GDM. RESULTS: Women diagnosed with GDM exhibited significantly higher levels of liver enzymes than those without GDM (all p < 0.05). The highest quartile of liver enzymes was associated with higher risk of GDM compared with the lowest quartile, with adjusted odds ratio (ORs) ranging from 2.76 to 8.11 (all p < 0.05). Moreover, the ORs of GDM increased linearly with liver enzymes level (all P for overall association <0.001). Furthermore, Back-propagation artificial neural network identified γ-gamma-glutamyl transferase (GGT) as accounting for the highest proportion in the ranking of GDM risk prediction weights (up to 20.8%). CONCLUSIONS: Single or total elevations of liver enzymes in early pregnancy could predict the GDM occurrence, in which GGT, alkaline Phosphatase, and aspartate aminotransferase were the three most important independent risk factors.

Tribological Effects of Quaternary Ammonium-Functionalized Montmorillonite as Water-Based Additives.

In this study, a water-soluble quaternary ammonium salt (QAS)-functionalized montmorillonite (MMT) was fabricated using a mechanochemical method as a high-performance water lubrication additive. The intercalation of QAS into the MMT layer expands the layer spacing of MMT, but does not affect the hydrophilicity of MMT. The ultrathin layer QAS-functionalized montmorillonite (QAS-MMT) demonstrated excellent water-stable dispersion and can be used as a water-based lubrication additive. Only 0.1% addition can reduce the friction coefficient by more than 71.4% and the wear volume by about 58.8% when compared to water, demonstrating its excellent friction reduction and antiwear performance. The frictional mechanism indicates that the physical adsorption film, together with the chemical reaction film, endows the QAS-MMT additives with outstanding tribological performance, provides excellent lubrication for the contact of steel/steel pairs, and prevents the steel surface from being further worn.

A 1,8-naphthimide-based Fluorescent Probe for Analyzing DMF/H2O Composition.

A novel 1,8-naphthalimide fluorescent probe (BNAS) containing 2-thiopheneethylamine moiety was designed and synthesized for analyzing the composition of N,N-dimethylformamide (DMF)/deionized water (H2O) mixtures. With the increase of DMF content, the fluorescence of the system was enhanced from dark to bright yellow-green. Taking 15% (volume) DMF content as the dividing point, the fluorescence intensity of the system at 535 nm showed two good linear relationships with the DMF content 1-15% and 15-99%, based on which the composition of the DMF/H2O mixtures with a volume ratio of 1/99-99/1 could be quickly and efficiently analyzed with high selectivity and sensitivity. BNAS can be applied in real sample assay and further be loaded onto filter paper to make a portable sensor. The mechanism of BNAS response to DMF/H2O composition was also explored.

Three Novel Rhodamine 6G-Based Colorimetric and Fluorescent pH Switches.

Three rhodamine 6G derivatives (REHA, RETA and REDA) were designed and synthesized by connecting rhodamine 6G and 3-methyl-2-thiophenal with hydrazine hydrate, ethylenediamine and diethylenetriamine, respectively. In CH3CN/H2O (50/50, v/v), the absorbance of REHA, RETA and REDA at 528 nm was suddenly enhanced by 3.2, 3.8 and 7.2 times within the pH range of 3.03-2.31, 3.05-2.32 and 3.06-2.34, respectively, and the solution changed from colorless to pink. Meanwhile, the maximal fluorescence intensity sharply increased by 53.9, 26.6 and 24.9 times in the pH range of 3.86-3.46, 3.88-3.47 and 3.89-3.48, respectively, and the solution changed from dark to bright yellow-green fluorescence. REHA, RETA and REDA can act as highly selective and sensitive colorimetric and fluorescent pH switches with good recyclability and anti-interference ability. The response mechanism of REHA, RETA and REDA to pH was studied by 1H NMR spectroscopy, and their application in indicating small pH changes in dyeing wastewater was investigated.

Prevalence and modifiable risk factors of cognitive frailty in patients with chronic heart failure in China: a cross-sectional study.

BACKGROUND: Cognitive frailty (CF) is currently a significant issue, and most of the associated factors discovered in current studies are not modifiable. Therefore, it is crucial to identify modifiable risk factors that can be targeted for interventions in patients with chronic heart failure (CHF). This study aimed to investigate the prevalence and modifiable risk factors of CF in CHF patients in China. METHODS: In this cross-sectional study, we sequentially enrolled patients diagnosed with CHF. CF served as the dependent variable, assessed through the Montreal Cognitive Assessment (MoCA) Scale and the FRAIL Scale. The independent variable questionnaire encompassed various components, including general demographic information, the Social Support Rating Scale (SSRS), the Simplified Nutrition Appetite Questionnaire (SNAQ), the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Logistic regression analysis was employed to identify independent factors contributing to CF. RESULTS: A total of 271 patients with CHF were included in the study. The overall prevalence of CF was found to be 49.4%, with 28.8% of patients exhibiting potentially reversible cognitive frailty and 20.7% showing reversible cognitive frailty. Among middle-young CHF patients, 10.7% had reversible cognitive frailty and 6.4% had potentially reversible cognitive frailty, with a prevalence of CF at 17.1%. Logistic regression analysis revealed that body mass index (OR = 0.826, 95%CI = 0.726-0.938), blood pressure level (OR = 2.323, 95%CI = 1.105-4.882), nutrition status (OR = 0.820, 95%CI = 0.671-0.979), and social support (OR = 0.745, 95%CI = 0.659-0.842) were independent factors associated with CF (p < 0.05). CONCLUSIONS: We observed a relatively high prevalence of CF among Chinese patients diagnosed with CHF. Many factors including BMI, blood pressure level, nutrition status, and social support emerging as modifiable risk factors associated with CF. We propose conducting clinical trials to assess the impact of modifying these risk factors. The outcomes of this study offer valuable insights for healthcare professionals, guiding them in implementing effective measures to improve the CF status in CHF patients during clinical practice.

Effects of inoculation and dry matter content on microbiome dynamics and metabolome profiling of sorghum silage.

Sorghum forage was ensiled for 90 days at two dry matter (DM) contents (27 vs. 39%) without or with Lactiplantibacillus plantarum inoculation. On day 90 of fermentation, silages were sampled to assess the microbial community dynamics and metabolome profile. L. plantarum inoculation improved silage quality, as shown by a lower pH and greater acetic acid concentration. Loss of DM remained unaffected by L. plantarum inoculation but was greater in low- vs. high-DM sorghum silages (14.4 vs. 6.62%). The microbiome analysis revealed that Pseudomonas congelans represented the dominant species of the epiphytic microbiota in both low- and high-DM sorghum forage before ensiling. However, L. buchneri represented the dominant species at the end of ensiling. Ensiling fermentation resulted in distinct metabolic changes in silages with varying DM content. In low-DM silages, ensiling fermentation led to the accumulation of 24 metabolites and a reduction in the relative concentration of 13 metabolites. In high-DM silages, ensiling fermentation resulted in an increase in the relative concentration of 26 metabolites but a decrease in the concentration of 8 metabolites. Compared to non-inoculated silages, L. plantarum inoculation resulted in an increased concentration of 3 metabolites and a reduced concentration of 5 metabolites in low-DM silages. Similarly, in high-DM silages, there was an elevation in the relative concentration of 3 metabolites, while a decrease in 7 other metabolites. Ten metabolites with bio-functional activity were identified, including chrysoeriol, isorhamnetin, petunidin 3-glucoside, apigenin, caffeic acid, gallic acid, p-coumaric acid, trans-cinnamic acid, herniarin, and 3,4-dihydroxy-trans-cinnamate. This study presents a comprehensive analysis of microbiome and metabolome profiling of sorghum forage during ensiling as a function of DM content and L. plantarum inoculation, with a particular emphasis on identifying metabolites that may possess bio-functional properties. KEY POINTS: • DM loss was not different by L. plantarum but higher in low- vs. high-DM silage. • L. buchneri dominated ensiling, regardless of DM level. • 10 metabolites with bio-functional activity were identified.

Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway.

Patulin (PAT) is one of the mycotoxins commonly found in agricultural products and fruits, and has obvious toxic effects on animals and humans. PAT has been found to cause myocardial toxicity and oxidative damage, but the mechanism of myocardial toxicity remained to be elucidated. We investigated the toxic effects and potential mechanisms of PAT on human cardiomyocytes and explored the effects of reactive oxygen species (ROS) on them. The study showed that treatment with PAT for 24 h decreased cell viability and superoxide dismutase (SOD) activity, and increased ROS and lactate dehydrogenase (LDH) levels. Moreover, in addition to detecting increased γ-H2AX expression and observing nuclear damage, the comet assay also showed increased DNA tail distance in the PAT-treated group, followed by an increase in phosphorylation of the p53 protein and p21 protein expression, and a decrease in CDK1 and Cyclin B1 protein expression, and G2/M phase arrest. In addition, PAT induced endoplasmic reticulum stress (ERS) and induced apoptosis, as evidenced by Ca2+ increase, ER enlargement and swelling, and upregulation of ERS-related genes and proteins expression, and increased expression of three apoptotic pathway proteins under ERS, including CHOP, JNK, and caspase-12. Meanwhile, N-acetylcysteine (NAC, a ROS scavenger) reversed the negative effects of PAT treatment on cells. These results clarify that excessive ROS production by PAT-treated AC16 cells not only causes DNA damage, leading to cell cycle arrest, but also causes ERS, which triggers apoptotic pathways to cause apoptosis.

Medication burden in patients with dialysis-dependent CKD: a systematic review.

This systematic review aimed to statistically profile the medication burden and associated influencing factors, and outcomes in patients with dialysis-dependent chronic kidney disease (DD-CKD). Studies of medication burden in patients with DD-CKD in the last 10 years from 1 January 2013 to 31 March 2024 were searched from PubMed, Embase, and Cochrane databases. Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) methodology checklist was used to evaluate quality and bias. Data extraction and combining from multiple groups of number (n), mean, and standard deviation (SD) were performed using R programming language (version4.3.1; R Core Team, Vienna, Austria). A total of 10 studies were included, and the results showed a higher drug burden in patients with DD-CKD. The combined pill burden was 14.57 ± 7.56 per day in hemodialysis (HD) patients and 14.63 ± 6.32 in peritoneal dialysis (PD) patients. The combined number of medications was 9.74 ± 3.37 in HD and 8 ± 3 in PD. Four studies described the various drug classes and their proportions, in general, antihypertensives and phosphate binders were the most commonly used drugs. Five studies mentioned factors associated with medication burden. A total of five studies mentioned medication burden-related outcomes, with one study finding that medication-related burden was associated with increased treatment burden, three studies finding that poor medication adherence was associated with medication burden, and another study finding that medication complexity was not associated with self-reported medication adherence. Limitations: meta-analysis was not possible due to the heterogeneity of studies.

Aberrant Activation of Notch1 Signaling in Glomerular Endothelium Induces Albuminuria.

RATIONALE: Glomerular capillaries are lined with a highly specialized fenestrated endothelium and contribute to the glomerular filtration barrier. The Notch signaling pathway is involved in regulation of glomerular filtration barrier, but its role in glomerular endothelium has not been investigated due to the embryonic lethality of animal models with genetic modification of Notch pathway components in the endothelium. OBJECTIVE: To determine the effects of aberrant activation of the Notch signaling in glomerular endothelium and the underlying molecular mechanisms. METHODS AND RESULTS: We established the ZEG-NICD1 (notch1 intracellular domain)/Tie2-tTA/Tet-O-Cre transgenic mouse model to constitutively activate Notch1 signaling in endothelial cells of adult mice. The triple transgenic mice developed severe albuminuria with significantly decreased VE-cadherin (vascular endothelial cadherin) expression in the glomerular endothelium. In vitro studies showed that either NICD1 (Notch1 intracellular domain) lentiviral infection or treatment with Notch ligand DLL4 (delta-like ligand 4) markedly reduced VE-cadherin expression and increased monolayer permeability of human renal glomerular endothelial cells. In addition, Notch1 activation or gene knockdown of VE-cadherin reduced the glomerular endothelial glycocalyx. Further investigation demonstrated that activated Notch1 suppression of VE-cadherin was through the transcription factors SNAI1 (snail family transcriptional repressor 1) and ERG (Ets related gene), which bind to the -373 E-box and the -134/-118 ETS (E26 transformation-specific) element of the VE-cadherin promoter, respectively. CONCLUSIONS: Our results reveal novel regulatory mechanisms whereby endothelial Notch1 signaling dictates the level of VE-cadherin through the transcription factors SNAI1 and ERG, leading to dysfunction of glomerular filtration barrier and induction of albuminuria. Graphic Abstract: A graphic abstract is available for this article.

Effect and mechanism of Fisetin on myocardial damage induced by Patulin.

OBJECTIVES OF THE STUDY: The aim of this study is to investigate whether fisetin can effectively reduce the myocardial damage induced by patulin. This study also aims to reveal the mechanism and target of fisetin in inhibiting myocardial damage. MATERIALS AND METHODS: Network pharmacology was used to screen the targets of fisetin on myocardial damage and the regulatory network of active ingredients-drug targets was constructed. GO and KEGG enrichment analyses were performed to screen out the key pathways and targets of fisetin on myocardial damage. Patulin induced apoptosis in H9c2 cardiomyocytes to verify the key targets. The mechanism of fisetin in inhibiting myocardial damage was determined. RESULTS: FIS can reduce the apoptosis of cardiomyocytes by protecting cardiomyocytes from PAT injury. According to the results of network pharmacology analysis, combined with enzyme activity detection and WB experiment, it was found that the mechanism of FIS to reduce myocardial damage may be related to the P53 signaling pathway, Caspase3/8/9 and Bax/Bcl-2. CONCLUSION: FIS plays a protective role in PAT-induced myocardial damage. On the one hand, FIS inhibits the protein overexpression of P53, Caspase-9 and Bax. On the other hand, FIS enhances the protein expression of Bcl-2.

The Diagnostic Performance of Laboratory Tests of Neurosyphilis: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: The gold standard for diagnosing neurosyphilis (NS) is currently unavailable; various laboratory parameters in cerebrospinal fluid (CSF) and blood can assist in the diagnosis. METHODS: PubMed, Embase, and the Cochrane Library were searched. Studies utilizing laboratory tests to assist in the diagnosis of NS were included. The pooled indicators for diagnostic performance and their respective 95% confidence intervals (CIs) were calculated. We used the superiority index to test the superiority of a diagnostic test. RESULTS: Eleven citations were included in the study. Albumin quotient, CSF-TPHA, CSF-EIA, CSF-LDH, CSF-WBC, CSF-CXCL13, FTA-ABS, CSF-PCR, RPR, CSF-TPPA, TRUST, and CSF-venereal diseases research laboratory (VDRL) were assessed in the studies included. The pooled estimates of sensitivity, specificity, AUC of SROC and their respective 95% CIs for CSF-TPPA and CSF-VDRL were 0.97 (0.17, 1.00), 0.84 (0.62, 0.95), 0.93 (0.91, 0.95) and 0.74 (0.59, 0.85), 0.99 (0.93, 1.00), 0.94 (0.91, 0.96), respectively. CSF-TPHA demonstrated the highest relative sensitivity. CSF-VDRL manifested the highest specificity. CSF-TPHA, TRUST, CSF-VDRL, CSF-EIA, and RPR ranked in the top five laboratory tests with superiority index. CONCLUSION: CSF-TPHA, TRUST, CSF-VDRL, CSF-EIA, and RPR indicate acceptable performance in detecting NS compared to other modalities. Comprehensive diagnostic strategies still play a significant role in the diagnosis of NS.

Update of dialysis initiation timing in end stage kidney disease patients: is it a resolved question? A systematic literature review.

BACKGROUND: The exact optimal timing of dialysis for ESKD patients remains unknown. This study systematically reviewed the available evidence with regard to the optimal initiation of maintenance dialysis in ESKD patients. METHODS: An electronic search was performed in Embase, PubMed and the Cochrane Library in order to find studies investigating associations between variables reference to "start of dialysis" and outcomes. Quality assessment and bias assessment were performed by the Newcastle-Ottawa scale and the ROBINSI tool. Due to the heterogeneity of studies, a meta-analysis could not be performed. RESULTS: Thirteen studies were included; four studies included only haemodialysis patients, three peritoneal dialysis, six both; study outcomes included mortality, cardiovascular events, technique failure, quality of life and others. Nine studies mainly focused on the optimal GFR of maintenance dialysis initiation; five studies showed none association between GFR and mortality or other adverse outcomes, two studies showed dialysis initiation at higher GFR levels were with poor prognosis, and 2 studies showed higher GFR levels with better prognosis. Three studies paid attention to comprehensive assessment of uremic signs and/or symptoms for optimal dialysis initiation; uremic burden based on 7 uremic indicators (hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate) were not associated with mortality; another equation (combination of sex, age, serum creatinine, blood urea nitrogen, serum albumin, haemoglobin, serum phosphorus, diabetes mellitus, and heart failure) based on fuzzy mathematics to assess the timing of haemodialysis initiation was accuracy to prognose 3-year survival; the third study found that volume overload or hypertension was associated with the highest risk for subsequent mortality. Two studies compared urgent or optimal start in dialysis, a study reported increased survival in optimal start patients, another reported no differences between Urgent-Start-PD and Early-Start-PD regarding 6-month outcomes. LIMITATIONS: Heterogeneity among the studies was quite high, with differences in sample size, variable and group characteristics; no RCT studies were included, which weakened the strength of evidences. CONCLUSIONS: The criteria for dialysis initiation were varied. Most studies proved that GFR at dialysis initiation was not associated with mortality, timing of dialysis initiation should not be based on GFR, assessments of volume load and patient's tolerance to volume overload are prospective approaches.

Platelet distribution width and the risk of unexplained recurrent pregnancy loss: a meta-analysis.

OBJECTIVE: Changes of platelet distribution width (PDW) have been observed in women with unexplained recurrent pregnancy loss (URPL). However, relevant previous studies showed inconsistent results. We performed a meta-analysis to comprehensively evaluate the association between PDW and URPL. METHODS: Observational studies reporting the difference of PDW between women with and without URPL were retrieved by searching PubMed, Embase, Web of Science, Wanfang, and CNKI. A random-effect model was used to pool the results by incorporating potential heterogeneity. RESULTS: Eleven case-control studies with 1847 women with URPL and 2475 healthy women were included. Age was matched for all studies between cases and controls. Pooled results showed women with URPL had significantly increased level of PDW (mean difference [MD]: 1.54%, 95% CI: 1.04 to 2.03, p < 0.05; I2 =77%). Subgroup analysis showed consistent result for URPL defined as ≥ 2 (MD: 1.45%, p = 0.003) and ≥ 3 (MD: 1.61%, p < 0.001) failed clinical pregnancies, and in studies compared to women with normal pregnancy (MD: 2.02%, p < 0.001) and non-pregnant healthy women (MD: 1.34%, p < 0.001). Results of the meta-analysis also showed that increment of PDW was associated with higher odds of URPL (per 1 unit, odds ratio: 1.26, 95% CI: 1.17 to 1.35, p < 0.001; I2 = 0%). CONCLUSIONS: Women with URPL had significantly increased levels of PDW compared to healthy women without URPL, which suggest that higher PDW may predict the risk of URPL.

Efficacy and safety of belimumab therapy in lupus nephritis: a systematic review and meta-analysis.

BACKGROUND: Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE), but the efficacy of belimumab for lupus nephritis (LN) is not clear. We conducted this meta-analysis and systematic review to compare the efficacy and safety of belimumab with those of conventional therapy for LN. METHODS: PubMed, EMBASE, Cochrane Library, Clinical Trials.gov were searched in 31 December 2022 to identify relevant adult human studies reporting effectiveness outcomes of belimumab in patients with LN. Review manager (RevMan 5.4) was used for data analysis with fixed effects model based on heterogeneities. RESULTS: Six randomized controlled trials (RCTs) were included in the quantitative analysis. A total of 2960 participants were identified. Belimumab plus standard therapy significantly improved total renal response rates (RR, 1.31; 95% CI, 1.11-1.53; p = 0.001) and complete renal RRs (1.47; 95% CI, 1.07-2.02; p = 0.02) compared with the control plus standard therapy group. It significantly reduced the risk of renal flare (RR, 0.51; 95% CI, 0.37-0.69; p < 0.001) and renal function worsening or progression to end-stage renal disease (ESRD) (RR, 0.56; 95% CI, 0.40-0.79; p = 0.001). When assessed with the incidence of adverse events, no significant differences between the two groups were observed for the occurrence of treatment-related adverse events (RR, 1.04; 95% CI, 0.99-1.09; p = 0.12). CONCLUSIONS: This meta-analysis showed that belimumab plus standard therapy was more effective and had a favorable safety in patients with LN.

Occurrence and fate of antibiotic-resistance genes and their potential hosts in high-moisture alfalfa silage treated with or without formic acid bactericide.

Silage as the main forage for ruminants could be a reservoir for antibiotic resistance genes (ARGs) through which these genes got access into the animals' system causing a latent health risk. This study employed metagenomics and investigated the ARGs' fate and transmission mechanism in high-moisture alfalfa silage treated with formic acid bactericide. The results showed that there were 22 ARGs types, in which multidrug, macrolide-lincosamide-streptogramine, bacitracin, beta-lactam, fosmidomycin, kasugamycin, and polymycin resistance genes were the most prevalent ARGs types in the ensiled alfalfa. The natural ensiling process increased ARGs enrichment. Intriguingly, after 5 days of ensiling, formic acid-treated silage reduced ARGs abundances by inhibiting host bacterial and plasmids. Although formic acid bactericide enhanced the fermentation characteristics of the high-moisture alfalfa by lowering silage pH, butyric acid concentration, dry matter losses and proteolysis, it increased ARGs abundances in alfalfa silage owing to increases in abundances of ARGs carriers and transposase after 90 days of ensiling. Notably, several pathogens like Staphylococcus, Clostridium, and Pseudomonas were inferred as potential ARGs hosts in high-moisture alfalfa silage, and high-moisture alfalfa silage may harbor a portion of the clinical ARGs. Fundamentally, microbes were distinguished as the foremost driving factor of ARGs propagation in ensiling microecosystem. In conclusion, although formic acid bactericide improved the fermentation characteristics of high-moisture alfalfa during ensiling and reduced ARGs enrichment at the initial ensiling stage, it increased ARGs enrichment at the end of ensiling.

Regarding reference state to identify priority areas for ecological restoration in a karst region.

Widespread degradation of natural ecosystems around the globe has resulted in several ecological problems. Ecological restoration is considered a global priority as an important means of mitigating ecosystem degradation and enhancing ecosystem services provision. Regarding ecosystem reference state is a prerequisite for ecological restoration. However, there were few studies focusing on how to regard reference state for ecological restoration, especially under a changing climate. Taking Guizhou Province, a typical karst region in China, as a case study area, in this study we firstly assessed ecosystem services under homogeneous climate conditions. Secondly, we defined the optimal ecosystem services as ecosystem reference state, and then evaluated restoration suitability under a comprehensive framework. Finally, ecological restoration priority areas (EPRAs), which included ecological reconstruction areas, assisted regeneration areas and conservation priority areas needing restoration, were identified by integrating restoration suitability and conservation priority areas. The results showed that the services of water conservation and habitat maintenance only increased less than 10% from 2001 to 2018. Identified ecological reconstruction areas and assisted regeneration areas covered 1078 km2 and 1159 km2 respectively. Additionally, 15 conservation priority areas with the total area of 18,507 km2 were identified as conservation priority areas needing restoration. Accounting for 11.78% of the total area, ERPAs were mostly located in the eastern part of Guizhou, including Qiandongnan, Tongren, and Zunyi. The approach proposed here for regarding ecosystem reference state after controlling climate variables and the framework for identifying ERPAs can provide a scientific reference for large-scale ecological restoration planning.

Comprehensive profiling of the metabolome in corn silage inoculated with or without Lactiplantibacillus plantarum using different untargeted metabolomics analyses.

Silage fermentation is a complicated biochemical process involving interactions between microbes and metabolites. However, the overall metabolome feature of ensiled forage and its response to lactic acid bacteria inoculation is poorly understood. Hence, in this study metabolome profiles of whole-plant corn silage inoculated with or without Lactiplantibacillus plantarum were characterised via solid-phase microextraction/gas chromatography/mass spectrometry (SPME-GC-MS), gas chromatography/time-of-flight mass spectrometry (GC-TOF-MS), and Liquid chromatography/Q Exactive HFX mass spectrometry (LC-QE-MS/MS) analysis. There were 2087 identified metabolites including 1143 reliably identified metabolites in fresh and ensiled whole-plant corn. After ensiling, the increased metabolites in whole-plant corn were mainly composed of organic acids, volatile organic compounds (VOC), benzene and substituted derivatives, carboxylic acids and derivatives, fatty acyls, flavonoids, indoles and derivatives, organooxygen compounds (including amines and amides), phenols, pyridines and derivatives, and steroids and steroid derivatives, which includes neurotransmitters and metabolites with aromatic, antioxidant, anti-inflammatory, and antimicrobial activities. Phenylacetaldehyde was the most abundant aromatic metabolite after ensiling. L-isoleucine and oxoproline were the major free amino acids in silage. Ensiling markedly increased the relative abundances of 3-phenyllactic acid, chrysoeriol, 6-O-acetylaustroinulin, acetylcholine, γ-aminobutyric acid, pyridoxine, and alpha-linoleic acid. Inoculation with L. plantarum remarkably changed silage VOC composition, and essential amino acids, 3-phenyllactic acid, and cinnamaldehyde compared with untreated silage. The present study does not only provide a deeper insight into metabolites of the ensiled whole-plant corn but also reveals metabolites with specific biological functions that could be much helpful in screening novel lactic acid bacteria to well ensile forages. Inoculation with L. plantarum significantly affects the metabolome in ensiled whole-plant corn.