An early and stable mouse model of polymyxin-induced acute kidney injury.

BACKGROUND: Polymyxins have been revived as a last-line therapeutic option for multi-drug resistant bacteria and continue to account for a significant proportion of global antibiotic usage. However, kidney injury is often a treatment limiting event with kidney failure rates ranging from 5 to 13%. The mechanisms underlying polymyxin-induced nephrotoxicity are currently unclear. Researches of polymyxin-associated acute kidney injury (AKI) models need to be more standardized, which is crucial for obtaining consistent and robust mechanistic results. METHODS: In this study, male C57BL/6 mice received different doses of polymyxin B (PB) and polymyxin E (PE, also known as colistin) by different routes once daily (QD), twice daily (BID), and thrice daily (TID) for 3 days. We continuously monitored the glomerular filtration rate (GFR) and the AKI biomarkers, including serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). We also performed histopathological examinations to assess the extent of kidney injury. RESULTS: Mice receiving PB (35 mg/kg/day subcutaneously) once daily exhibited a significant decrease in GFR and a notable increase in KIM-1 two hours after the first dose. Changes in GFR and KIM-1 at 24, 48 and 72 h were consistent and demonstrated the occurrence of kidney injury. Histopathological assessments showed a positive correlation between the severity of kidney injury and the changes in GFR and KIM-1 (Spearman's rho = 0.3167, P = 0.0264). The other groups of mice injected with PB and PE did not show significant changes in GFR and AKI biomarkers compared to the control group. CONCLUSION: The group receiving PB (35 mg/kg/day subcutaneously) once daily consistently developed AKI at 2 h after the first dose. Establishing an early and stable AKI model facilitates researches into the mechanisms of early-stage kidney injury. In addition, our results indicated that PE had less toxicity than PB and mice receiving the same dose of PB in the QD group exhibited more severe kidney injury than the BID and TID groups.

Urolithin A alleviates cell senescence by inhibiting ferroptosis and enhances corneal epithelial wound healing.

Purpose: To analyze the therapeutic effect and mechanism of Urolithin A (UA) on delayed corneal epithelial wound healing. Methods: The C57BL/6 mice were continuously exposed to hyperosmotic stress (HS) for 7 days followed by the removal of central corneal epithelium to establish a delayed corneal epithelial wound healing model in vivo. In vitro, the human corneal epithelial cell line (HCE-T) was also incubated under HS. UA was administered in vivo and in vitro to study its effects on corneal epithelial cells. Senescence-associated ß-galactosidase (SA-ß-gal) staining was performed to detect the level of cell senescence. Transcriptome sequencing (RNA-seq) was conducted to elucidate the molecular mechanism underlying the effect of UA on corneal epithelial repair. Additionally, the expression of senescence-related and ferroptosis-related genes and the levels of lipid peroxides (LPO) and malondialdehyde (MDA) were measured. Results: Hyperosmotic stress (HS) significantly increased the proportion of SA-ß-gal staining positive cells in corneal epithelial cells and upregulated the expression of p16 and p21 (p < 0.0001). Topical application of UA decreased the accumulation of senescent cells in corneal epithelial wounds and promoted epithelial wound healing. The results of RNA-seq of HS-induced corneal epithelial cells showed that the ferroptosis pathway was significantly dysregulated. Further investigation revealed that UA decreased the level of oxidative stress in HCE-T cells, including the levels of LPO and MDA (p < 0.05). Inhibition of ferroptosis significantly prevented cellular senescence in HS-induced HCE-T cells. Conclusion: In this study, UA promoted HS-induced delayed epithelial wound healing by reducing the senescence of corneal epithelial cells through the inhibition of ferroptosis.

Poor sample size reporting quality and insufficient sample size in economic evaluations conducted alongside pragmatic trials: A cross-sectional survey.

OBJECTIVES: Economic evaluation outcomes are seldom taken into consideration during the process of sample size calculation in pragmatic trials. The reporting quality of sample size and information on its calculation in economic evaluations well suited to pragmatic randomized controlled trials (pRCTs) remain unknown. This study aims to assess the sample size and power of economic evaluations in pRCTs. STUDY DESIGN AND SETTING: We conducted a cross-sectional survey using data of pRCTs available from PubMed and OVID from 1 January 2010 to 24 April 2022. Two groups of independent reviewers identified articles; three groups of reviewers each extracted the data. Descriptive statistics presented the general characteristics of included studies. Statistical power analyses were performed on clinical and economic outcomes with sufficient data. RESULTS: The electronic search identified 715 studies; 152 met the inclusion criteria and, of these, 26 were available for power analysis. Only 9 out of 152 trials (5.9%) considered economic outcomes when estimating sample size, and only one adjusted the sample size accordingly. Power values for trial-based economic evaluations, and clinical trials ranged from 2.56% to 100%, 3.21% to 100%, respectively. Regardless of the perspectives, in 14 among 26 studies (53.8%), the power values of economic evaluations for quality-adjusted life years (QALYs) were lower than those of clinical trials for primary endpoints (PEs). In 11 out of 24 (45.8%) and 8 from 13 (61.5%) studies, power values of economic evaluations for QALYs were lower than those of clinical trials for PEs from the healthcare and societal perspectives, respectively. Power values of economic evaluations for non-QALYs from the healthcare and societal perspectives were potentially higher than those of clinical trials in 3 from a total of 4 studies (75%). The power values for economic outcomes in Q1 were not significantly higher than those for other journal impact factor quartile categories. CONCLUSIONS: Theoretically, pragmatic trials with concurrent economic evaluations can provide real-world evidence for healthcare decision makers. However, in pRCT-based economic evaluations, limited consideration and inadequate reporting of sample-size calculations for economic outcomes could negatively affect the results' reliability and generalisability. To avoid misleading decisions made based on study results, we recommend that future pragmatic trials with economic evaluations should report how sample sizes are determined or adjusted based on the economic outcomes in their protocols to enhance their transparency and evidence quality.

SIRT6 alleviates senescence induced by Porphyromonas gingivalis in human gingival fibroblasts.

OBJECTIVE: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs). DESIGN: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related ß-galactosidase (SA-ß-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry. RESULTS: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-ß-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05). CONCLUSIONS: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway.

Screening high-efficiency promoter to construct trans-vp28 gene Anabaena sp. PCC7120 against white spot syndrome virus of Litopenaeus vannamei.

This study aimed to select high-quality promoters to construct trans-vp28 gene Anabaena sp. PCC7120 and feed Litopenaeus vannamei to assess the effect of L.vannamei against white spot syndrome virus (WSSV). Transgenic algae were created using five plasmids containing PrbcL, Pcpc560, Ptrc, Ptac, and PpsbA. According to the gene expression efficiency and the growth index of transgenic algae, Pcpc560 was determined to be the most efficient promoter. Shrimps were continuously fed trans-vp28 gene Anabaena sp. PCC7120 for one week and then challenged with WSSV. After the challenge, the transgenic algae group (vp28-7120 group) was continuously immunized [continuous immunization for 0 days (vp28-7120-0d); continuous immunization for 2 days (vp28-7120-2d); continuous immunization for 4 days (vp28-7120-4d)]. After seven days, the daily survival rate of each experimental group was continuously tracked. Following the viral challenge, the hepatopancreas samples were assayed for their levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), thioredoxin peroxidase (TPX), acid phosphatase (ACP), and alkaline phosphatase (AKP) at varying time intervals. In comparison to the positive control group (challenge and no vaccination) and the wild-type group (challenge, fed wild-type Anabaena sp. PCC7120), the vp28-7120 group (challenge, fed trans-vp28 gene Anabaena sp. PCC7120) exhibited a remarkable increase in survival rates, reaching 50 % (vp28-7120-0d), 76.67 % (vp28-7120-2d), and 80 % (vp28-7120-4d). Furthermore, the vp28-7120 group consistently displayed significantly higher activities of SOD, CAT, GSH-Px, ACP, and AKP, while exhibiting notably lower TPX activity, when compared to the control group. These results indicate that the Pcpc560 promoter effectively elevated the expression level of the exogenous vp28 gene and spurred the growth of the trans-vp28 gene Anabaena sp. PCC7120. Consequently, trans-vp28 gene Anabaena sp. PCC7120 significantly bolstered the immunity of L.vannamei. Therefore, utilizing the Pcpc560 promoter to develop trans-vp28 gene Anabaena sp. PCC7120 based oral vaccine is highly beneficial for industrial-scale cultivation, advancing its commercialization prospects.

Sabulicella glaciei sp. nov., Isolated from Glacier, and Reclassification of Roseomonas rubea, Roseomonas ponticola and Roseomonas oleicola as Neoroseomonas rubea comb. nov., Falsiroseomonas ponticola comb. nov. and Falsiroseomonas oleicola comb. nov.

A Gram-stain-negative, short rod-shaped strain, MDT2-1-1T, was isolated from cryoconite samples collected from the Midui glacier in Tibet, China. It grew aerobically from 7 to 40 °C, within a pH range of 6.0-10.0, and in NaCl concentration of 0 to 1.0% (w/v). The pairwise 16S rRNA gene sequence similarity, average nucleotide identity and digital DNA-DNA hybridization values between strains MDT2-1-1T and Sabulicella rubraurantiaca SYSU D01096T were 99.4%, 89.7% and 38.9%, respectively. Considering the results from phylogeny, phenotypic and genotypic data, strain MDT2-1-1T (=CGMCC 1.11170T = NBRC 110485T) was suggested to represent a novel species of the genus Sabulicella, for which the name Sabulicella glaciei sp. nov. is proposed. Furthermore, based on the phylogenomic analysis, it is recommended that Roseomonas rubea, Roseomonas ponticola and Roseomonas oleicola be reclassified as Neoroseomonas rubea comb. nov., Falsiroseomonas ponticola comb. nov. and Falsiroseomonas oleicola comb. nov., respectively. Considering the illegitimate status of the genera names Pararoseomonas and Pseudoroseomonas, the species within the genera Pararoseomonas and Pseudoroseomonas should be transferred to Muricoccus and Teichococcus, respectively. Therefore, we proposed the following new combinations: Muricoccus aeriglobus comb. nov., Muricoccus aerilatus comb. nov., Muricoccus harenae comb. nov., Muricoccus nepalensis comb. nov., Muricoccus pecuniae comb. nov., Muricoccus radiodurans comb. nov., Muricoccus vinaceus comb. nov., Teichococcus aerofrigidensis comb. nov., Teichococcus aerophilus comb. nov., Teichococcus aestuarii comb. nov., Teichococcus cervicalis comb. nov., Teichococcus coralli comb. nov., Teichococcus deserti comb. nov., Teichococcus globiformis comb. nov., Teichococcus hibiscisoli comb. nov., Teichococcus musae comb. nov., Teichococcus oryzae comb. nov., Teichococcus rhizosphaerae comb. nov., Teichococcus ruber comb. nov., Teichococcus suffuscus comb. nov., Teichococcus vastitatis comb. nov., and Teichococcus wenyumeiae comb. nov.

[Autosomal recessive polycystic kidney disease in a girl]. / å¸¸æŸ“è‰²ä½“éšæ€§é—ä¼ æ€§å¤šå›Šè‚¾1例.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis. Upon admission, gastroscopy revealed esophageal and gastric varices. Abdominal CT scan, MRI, and color Doppler ultrasound suggested cirrhosis, intrahepatic bile duct dilation, and bilateral kidney enlargement. Genetic testing identified compound heterozygous mutations in the PKHD1 gene: c.2264C>T (p.Pro755Leu) and c.1886T>C (p.Val629Ala). The c.2264C>T (p.Pro755Leu) mutation is a known pathogenic variant with previous reports, while c.1886T>C (p.Val629Ala) is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2. The child was diagnosed with autosomal recessive polycystic kidney disease. In children presenting with gastrointestinal bleeding without obvious causes, particularly those with liver or kidney disease, consideration should be given to the possibility of autosomal recessive polycystic kidney disease, and genetic testing should be conducted for definitive diagnosis when necessary.

Impact of web-based positive psychological intervention on emotions, psychological capital, and quality of life in gastric cancer patients on chemotherapy.

BACKGROUND: Gastric cancer is a malignant digestive tract tumor that originates from the epithelium of the gastric mucosa and occurs in the gastric antrum, particularly in the lower curvature of the stomach. AIM: To evaluate the impact of a positive web-based psychological intervention on emotions, psychological capital, and quality of survival in gastric cancer patients on chemotherapy. METHODS: From January 2020 to October 2023, 121 cases of gastric cancer patients on chemotherapy admitted to our hospital were collected and divided into a control group (n = 60) and an observation group (n = 61) according to the admission order. They were given either conventional nursing care alone and conventional nursing care combined with web-based positive psychological interventions, respectively. The two groups were compared in terms of negative emotions, psychological capital, degree of cancer-caused fatigue, and quality of survival. RESULTS: After intervention, the number of patients in the observation group who had negative feelings toward chemotherapy treatment was significantly lower than that of the control group (P < 0.05); the Positive Psychological Capital Questionnaire score was considerably higher than that of the control group (P < 0.05); the degree of cancer-caused fatigue was significantly lower than that of the control group (P < 0.05); and the Quality of Life Scale for Cancer Patients (QLQ-30) score was significantly higher than that of the control group (P < 0.05). CONCLUSION: Implementing a web-based positive psychological intervention for gastric cancer chemotherapy patients can effectively improve negative emotions, enhance psychological capital, and improve the quality of survival.

Development and validation of a nomogram for predicting rapid relapse in triple-negative breast cancer patients treated with neoadjuvant chemotherapy.

Background: Triple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. This study aimed to develop and validate a nomogram based on clinicopathological characteristics to predict rapid relapse in TNBC patients treated with neoadjuvant chemotherapy (NAC) first. Methods: The clinicopathological data of 504 TNBC patients treated with NAC first in Tianjin Medical University Cancer Hospital were analyzed retrospectively, with 109 rapid relapsed patients, and 395 non-rapid relapsed patients, respectively. Based on clinicopathologic characteristics, and follow-up data were analyzed. The independent predictors of clinicopathological characteristics were identified by logistic regression analysis and then used to build a nomogram. The concordance index (C-index), the area under the curve (AUC) of receiver operating characteristic (ROC), and calibration plots were used to evaluate the performance of the model. Results: Univariate and multivariate logistic regression analyses showed that age at diagnosis (age≥50 years, OR = 0.325,95% CI:0.137-0.771), Nodal staging (N3 staging, OR = 13.669,95% CI:3.693-50.592),sTIL expression levels (sTIL intermediate expression, OR = 0.272,95% CI:0.109-0.678; sTIL high expression, OR = 0.169,95% CI:0.048-0.594), and NAC response (ORR, OR = 0.059,95% CI:0.024-0.143) were independent predictors of rapid relapse in TNBC patients treated with NAC firstly. Among these independent predictors, age ≥ 50 years, sTIL intermediate expression, sTIL high expression, and ORR in NAC were independent protective factors for rapid relapse in TNBC NAC patients. N3 staging was an independent risk factor for rapid relapse in TNBC NAC patients. The ROC curve, calibration curve, and decision curve analysis were used to validate the model. The C-Index of the training sets and validation sets were 0.938 and 0.910, respectively. The Brier scores of the training sets and validation sets were 0.076 and 0.097, respectively. Conclusion: This study developed and verified a nomogram for predicting rapid relapse in TNBC NAC patients, and the predictive model had high discrimination and accuracy.

A preliminary study of renal function for renal artery stenosis using multiparametric magnetic resonance imaging.

OBJECTIVE: To comprehensively evaluate the renal structure and function of patients with renal artery stenosis (RAS) using multiparametric magnetic resonance imaging (MRI), and analyze the correlation between magnetic resonance (MR) parameters and renal function. MATERIALS AND METHODS: Renal multiparametric MRI was conducted on 62 patients with RAS utilizing a Philips Ingenia CX 3.0 T MRI system. The scanning protocols encompassed arterial spin labeling, phase contrast MRI, diffusion weighted imaging, T1 mapping, and blood oxygen level-dependent MRI. All patients underwent radionuclide renal dynamic imaging to calculate the glomerular filtration rate (GFR) for assessing renal function. RESULTS: Most MR parameters were correlated with GFR: renal parenchymal volume (R = 0.603), whole kidney renal blood flow (RBF) (R = 0.192), renal cortical RBF (R = 0.294), renal artery mean velocity (R = 0.593), stroke volume (R = 0.599), mean flux (R = 0.629), renal cortical apparent diffusion coefficient (ADC) (R = 0.466), medullary ADC (R = 0.332), cortical T1 value (R = - 0.206), corticomedullary T1 difference (R = 0.204), cortical T2* value (R = 0.448), and medullary T2* value (R = 0.272). The best prediction model for GFR using multiparametric MRI was obtained, including renal PV, whole kidney RBF, cortical RBF, mean velocity, mean flux, and CMD T1. CONCLUSION: Multiparametric MRI is a novel noninvasive examination method that can effectively and comprehensively assess the renal structure and function of RAS.

Stimulation of an entorhinal-hippocampal extinction circuit facilitates fear extinction in a post-traumatic stress disorder model.

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging due to the fragile nature of fear extinction, for which ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed fear extinction. Gamma entrainment of vCA1 by deep brain stimulation (DBS) or noninvasive transcranial alternating current stimulation (tACS) of LEC persistently enhanced the PV-IN activity in vCA1, thereby promoting fear extinction. These results demonstrate that the LEC-vCA1 pathway forms a top-down motif to empower low gamma-band oscillations that facilitate fear extinction. Finally, application of low gamma DBS and tACS to a mouse model with persistent PTSD showed potent efficacy, suggesting that the dedicated LEC-vCA1 pathway can be stimulated for therapy to remove traumatic memory trace.

DJ-1: Potential target for treatment of myocardial ischemia-reperfusion injury.

Ischemic heart disease (IHD) is a significant global health concern, resulting in high rates of mortality and disability among patients. Although coronary blood flow reperfusion is a key treatment for IHD, it often leads to acute myocardial ischemia-reperfusion injury (IRI). Current intervention strategies have limitations in providing adequate protection for the ischemic myocardium. DJ-1, originally known as a Parkinson's disease related protein, is a highly conserved cytoprotective protein. It is involved in enhancing mitochondrial function, scavenging reactive oxygen species (ROS), regulating autophagy, inhibiting apoptosis, modulating anaerobic metabolism, and exerting anti-inflammatory effects. DJ-1 is also required for protective strategies, such as ischemic preconditioning, ischemic postconditioning, remote ischemic preconditioning and pharmacological conditioning. Therefore, DJ-1 emerges as a potential target for the treatment of myocardial IRI. Our comprehensive review delves into its protective mechanisms in myocardial IRI and the structural foundations underlying its functions.

Blueberry extract attenuates DSS-induced inflammatory bowel disease in mice through inhibiting ER stress-mediated colonic apoptosis in mice.

Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.

N-Difluoroacetylhexosamine as a Substrate-Engineering Precursor for Glycosylation Reactions.

We present the application of N-difluoroacetylglucosamine (GlcNDFA) in a chemical evolution strategy to synthesize oligosaccharides. In comparison to conventional N-trifluoroacetylglucosamine, GlcNDFA exhibits superior substrate compatibility with glycosyltransferases as well as stability in aqueous environments. Using our 16-step assembly line, GlcNDFA can be used to produce homogeneous dekaparin, a heparin-like medication, with a yield of 62.2%. This underscores the significant potential of GlcNDFA as a chemical evolution precursor in the precise synthesis of structurally defined polysaccharides.

ß-Cyclodextrin-optimized supramolecular nanovesicles enhance the droplet/foliage interface interactions and inhibition of succinate dehydrogenase (SDH) for efficient treatment of fungal diseases.

BACKGROUND: Plant fungal diseases present a major challenge to global agricultural production. Despite extensive efforts to develop fungicides, particularly succinate dehydrogenase inhibitors (SDHIs), their effectiveness is often limited by poor retention of fungicide droplets on hydrophobic leaves. The off-target losses and unintended release cause fungal resistance and severe environmental pollution. RESULTS: To update the structure of existing SDHIs and synchronously realize the efficient utilization, we have employed a sophisticated supramolecular strategy to optimize a structurally novel SDH inhibitor (AoH25), creating an innovative supramolecular SDH fungicide (AoH25@ß-CD), driven by the host-guest recognition principle between AoH25 and ß-cyclodextrin (ß-CD). Intriguingly, AoH25@ß-CD self-assembles into biocompatible supramolecular nanovesicles, which reinforce the droplet/foliage (liquid-solid) interface interaction and the effective wetting and retention on leaf surfaces, setting the foundation for enhancing fungicide utilization. Mechanistic studies revealed that AoH25@ß-CD exhibited significantly higher inhibition of SDH (IC50 = 1.56 µM) compared to fluopyram (IC50 = 244.41 µM) and AoH25 alone (IC50 = 2.29 µM). Additionally, AoH25@ß-CD increased the permeability of cell membranes in Botryosphaeria dothidea, facilitating better penetration of active ingredients into pathogenic cells. Further experimental outcomes confirmed that AoH25@ß-CD was 88.5% effective against kiwifruit soft rot at a low-dose of 100 µg mL-1, outperforming commercial fungicides such as fluopyram (52.4%) and azoxystrobin (65.4%). Moreover, AoH25@ß-CD showed broad-spectrum bioactivity against oilseed rape sclerotinia, achieving an efficacy of 87.2%, outstripping those of fluopyram (48.7%) and azoxystrobin (76.7%). CONCLUSION: This innovative approach addresses key challenges related to fungicide deposition and resistance, improving the bioavailability of agricultural chemicals. The findings highlight AoH25@ß-CD as a novel supramolecular SDH inhibitor, demonstrating its potential as an efficient and sustainable solution for plant disease management.

Dynamic changes in the real-time glomerular filtration rate and kidney injury markers in different acute kidney injury models.

In this study, we dynamically monitored the glomerular filtration rate and other assessment of renal function and markers of injury in various mice models of acute kidney injury. Male C57BL/6 mice were utilized to establish acute kidney injury models of sepsis, ischemia reperfusion, cisplatin, folic acid, aristolochic acid and antibiotic. In addition to the real time glomerular filtration rate, renal LCN-2 and HAVCR-1 mRNA expression levels, and serum creatinine, urea nitrogen and cystatin c levels were also used to evaluate renal function. In addition, the protein levels of LCN-2 and HAVCR-1 in renal, serum and urine were measured. Our results demonstrated that the changes in biomarkers always lagged the real time glomerular filtration rate during the progression and recovery of renal injury. Cystatin-c can reflect renal injury earlier than other markers, but it remains higher in the recovery stage. Perhaps the glomerular filtration rate does not reflect the greater injury caused by vancomycin plus piperacillin.

Site-directed mutagenesis leads to the optimized transglycosylation activity of endo-beta-N-acetylglucosaminidase from Trypanosoma brucei.

Endo-ß-N-acetylglucosaminidases (ENGases) are pivotal enzymes in the degradation and remodeling of glycoproteins, which catalyze the cleavage or formation of ß-1,4-glycosidic bond between two N-acetylglucosamine (GlcNAc) residues in N-linked glycan chains. It was investigated that targeted mutations of amino acids in ENGases active site may modulate their hydrolytic and transglycosylation activities. Endo-Tb, the ENGase derived from Trypanosoma brucei, belongs to the glycoside hydrolase family 85 (GH85). Our group previously demonstrated that Endo-Tb exhibits hydrolytic activity toward high-mannose and complex type N-glycans and preliminarily confirmed its transglycosylation potential. In this study, we further optimized the transglycosylation activity of recombinant Endo-Tb by focusing on the N536A, E538A and Y576F mutants. A comparative analysis of their transglycosylation activity with that of the wild-type enzyme revealed that all mutants exhibited enhanced transglycosylation capacity. The N536A mutant exhibited the most pronounced improvement in transglycosylation activity with a significant reduction in hydrolytic activity. It is suggested that Endo-Tb N536A possesses the potential as a tool for synthesizing a wide array of glycoconjugates bearing high-mannose and complex type N-glycans.

Research progress in the biosynthesis of xylitol: feedstock evolution from xylose to glucose.

Xylitol, as an important food additive and fine chemical, has a wide range of applications, including food, medicine, chemical, and feed. This review paper focuses on the research progress of xylitol biosynthesis, from overcoming the limitations of traditional chemical hydrogenation and xylose bioconversion, to the full biosynthesis of xylitol production using green and non-polluting glucose as substrate. In the review, the molecular strategies of wild strains to increase xylitol yield, as well as the optimization strategies and metabolic reconfiguration during xylitol biosynthesis are discussed. Subsequently, on the basis of existing studies, the paper further discusses the current status of research and future perspectives of xylitol production using glucose as a single substrate. The evolution of raw materials from xylose-based five-carbon sugars to glucose is not only cost-saving, but also safe and environmentally friendly, which brings new opportunities for the green industrial chain of xylitol.

The role of left atrium posterior wall isolation in patients undergoing catheter ablation for atrial fibrillation.

The posterior left atrium (LAPW) is an important substrate for initiation and maintenance of atrial fibrillation (AF). While it has been proposed as a potential target for preventing recurrence of atrial tachyarrhythmias, it remains unclear whether electrical silence of LAPW offers additional benefits over pulmonary vein isolation (PVI) alone. We conducted a systematic review of PubMed, Medline, Embase, and Cochrane databases and identified 21 eligible studies, encompassing 1,514 patients assigned to PVI + posterior wall isolation (PWI) group and 1,629 patients assigned to PVI group. Over a median follow-up of 12 months, adjunctive PWI significantly improved the atrial tachyarrhythmia-free survival by 14% in comparison to PVI alone [relative risk (RR): 1.14, 95% confidence interval (CI): 1.04 to 1.25, p=0.004]. This improvement was mainly attributed to a pronounced benefit for patients with persistent AF. In addition, patients undergoing PVI+PWI had a longer procedure time [weighted mean difference (WMD): 23.85, 95% CI: 12.68 to 35.01, p<0.001], ablation time (WMD: 9.27, 95% CI: 5.19 to 13.54, p<0.001), and a nearly negligible increase in fluoroscopic exposure (WMD: 2.69, 95% CI: -0.23 to 5.62, p=0.071). There was no increased risk of procedure-related complications between these approaches (RR: 1.06, 95% CI: 0.71 to 1.57, p=0.787). Compared with PVI alone, PWI adjunctive to PVI exhibited a higher procedure success of sinus rhythm maintenance in persistent AF during an index catheter ablation. Meanwhile, elongated procedure time and ablation time did not compromise the safety of extensive ablation strategy with additional PWI.