Cadmium causes cerebral mitochondrial dysfunction through regulating mitochondrial HSF1.

Mitochondria, as the powerhouse of the cell, play a vital role in maintaining cellular energy homeostasis and are known to be a primary target of cadmium (Cd) toxicity. The improper targeting of proteins to mitochondria can compromise the normal functions of the mitochondria. However, the precise mechanism by which protein localization contributes to the development of mitochondrial dysfunction induced by Cd is still not fully understood. For this research, Hy-Line white variety chicks (1-day-old) were used and equally distributed into 4 groups: the Control group (fed with a basic diet), the Cd35 group (basic diet with 35 mg/kg CdCl2), the Cd70 group (basic diet with 70 mg/kg CdCl2) and the Cd140 group (basic diet with 140 mg/kg CdCl2), respectively for 90 days. It was found that Cd caused the accumulation of heat shock factor 1 (HSF1) in the mitochondria, and the overexpression of HSF1 in the mitochondria led to mitochondrial dysfunction and neuronal damage. This process is due to the mitochondrial HSF1 (mtHSF1), causing mitochondrial fission through the upregulation of dynamin-related protein 1 (Drp1) content, while inhibiting oligomer formation of single-stranded DNA-binding protein 1 (SSBP1), resulting in the mitochondrial DNA (mtDNA) deletion. The findings unveil an unforeseen role of HSF1 in triggering mitochondrial dysfunction.

Characteristics and Functions of Dominant Yeasts Together with Their Applications during Strong-Flavor Baijiu Brewing.

Yeasts are pivotal brewing microbes that are associated with the flavor and quality of Chinese baijiu, yet research on dominant yeasts in strong-flavor baijiu brewing remains limited. In this study, Saccharomyces cerevisiae, Pichia kudriavzevii, and Kazachstania bulderi were identified as predominated yeasts in strong-flavor baijiu. Each strain showed distinct characteristics in ethanol resistance, thermal tolerance, and lactic acid tolerance, severally. S. cerevisiae FJ1-2 excelled in ethanol and ethyl ester production, P. kudriavzevii FJ1-1 in ethyl acetate, and K. bulderi FJ1-3 in lactic acid generation. Subsequently, the reinforced Fuqu of each yeast were severally prepared for application in baijiu brewing to verify their functions. Results revealed that the relative abundance of fortified yeast in each group rose. Pichia, Kazachstania, and Saccharomyces emerged as the core microbe for each group, respectively, by co-occurrence network analysis, influencing the microbiota to regulate flavor substances. In short, P. kudriavzevii FJ1-1 enhanced ethyl acetate. K. bulderi FJ1-3 improved ethyl caproate production and decreased levels of ethyl acetate and higher alcohols by modulating yeast community between Pichia and Saccharomyces. This is a systematic endeavor to study the functions of yeasts of strong-flavor baijiu, providing a solid basis for improving baijiu quality.

A High-Entropy Oxyhydroxide with a Graded Metal Network Structure for Efficient and Robust Alkaline Overall Water Splitting.

Designing high-entropy oxyhydroxides (HEOs) electrocatalysts with controlled nanostructures is vital for efficient and stable water-splitting electrocatalysts. Herein, a novel HEOs material (FeCoNiWCuOOH@Cu) containing five non-noble metal elements derived by electrodeposition on a 3D double-continuous porous Cu support is created. This support, prepared via the liquid metal dealloying method, offers a high specific surface area and rapid mass/charge transfer channels. The resulting high-entropy FeCoNiWCuOOH nanosheets provide a dense distribution of active sites. The heterostructure between Cu skeletons and FeCoNiWCuOOH nanosheets enhances mass transfer, electronic structure coupling, and overall structural stability, leading to excellent activities in the oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and water splitting reaction. At 10 mA cm-2, the overpotentials for OER, HER, and water splitting in 1.0 m KOH solution are 200, 18, and 1.40 V, respectively, outperforming most current electrocatalysts. The catalytic performance remains stable even after operating at 300 mA cm-2 for 100, 100, and over 1000 h, correspondingly. This material has potential applications in integrated hydrogen energy systems. More importantly, density functional theory (DFT) calculations demonstrate the synergy of the five elements in enhancing water-splitting activity. This work offers valuable insights for designing industrial water electrolysis systems.

Numerical simulation and in vitro experimental study of the hemodynamic performance of vena cava filters with helical forms.

Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid-structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement.

Mindful breathing for cancer pain: efficacy of a single 20-minute session - a randomised controlled study.

OBJECTIVES: Cancer pain is a prevalent and challenging symptom affecting a significant number of patients globally, with inadequate control remaining a substantial challenge despite advancements in pain management. Non-pharmacological interventions, including mindfulness-based approaches, have shown promise in alleviating cancer-related pain. This study aimed to explore the efficacy of a single session of 20-minute mindful breathing in reducing pain among patients with cancer. METHODS: A randomised controlled study was conducted at the University of Malaya Medical Centre, Malaysia, involving adult cancer inpatients with a pain score of ≥4/10. Participants were randomly assigned to a 20-minute mindful breathing intervention or a 20-minute supportive listening control group. Outcome measures included pain intensity, pain unpleasantness and Hospital Anxiety and Depression Scale score, assessed before and after the intervention. RESULTS: The 20-minute mindful breathing sessions demonstrated significant efficacy in reducing pain intensity, pain unpleasantness and anxiety compared with the control group. CONCLUSION: This research broadens the repertoire of cancer pain management by highlighting the rapid and holistic benefits of a single session of 20-minute mindful breathing. The findings suggest the potential integration of brief mindfulness exercises into routine cancer care to enhance pain management and overall well-being.

Synthesis, biological activities and mechanistic studies of C20-ketone pachysandra alkaloids as anti-hepatocellular carcinoma agents.

The pachysandra alkaloids found in Sarcococca ruscifolia demonstrate notable anti-hepatocellular carcinoma activity. Despite their efficacy, the structural diversity of these compounds remains limited, and their precise antitumor mechanism is still unclear. In pursuit of identifying novel lead compounds with high efficacy and low toxicity for combating hepatocellular carcinoma, twenty-three compounds of C20-ketone pachysandra alkaloid derivatives were designed and synthesized by using 3-dimethylamine pachysandra alkaloids as scaffolds. Subsequent in vitro anticancer activity experiments showed that synthetic pachysandra alkaloids had a stronger effect on HepG2 cells than did their natural counterparts, with low toxicity and high selectivity. The most potent derivative, 6k, had an IC50 value of 0.75 µM, demonstrating 25.7-fold greater anticancer activity than sarcovagine D against HepG2 cells. Through network pharmacology and molecular docking analysis, it was revealed that synthetic pachysandra alkaloids may exert their effects by inhibiting the JAK2/STAT3 pathway, thereby preventing the proliferation of liver cancer cells. Further research through scratch tests, immunofluorescence experiments, and Western blot analysis revealed that compound 6k effectively inhibited the migration of HepG2 cells and induced mitochondria-mediated intrinsic apoptosis of HepG2 cells by regulating the JAK2/STAT3 signaling pathway. The aforementioned results indicate that compound 6k could be developed as a potential candidate for the treatment of hepatocellular carcinoma.

Protective effects of fructose-1,6-bisphosphate postconditioning on myocardial ischemia-reperfusion injury in patients undergoing valve replacement：a randomized, double-blind, placebo-controlled clinical trial.

Legend of Graphical Abstract: The figure describes the serum CK-MB concentrations in the FDP and NS groups at 4, 24, 48, and 72 h postoperatively. OBJECTIVES: Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1, 6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. METHODS: Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), alpha-hydroxybutyrate dehydrogenase (α-HBDH) and cardiac troponin I (cTnI), the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, ICU and postoperative hospitalization. RESULTS: Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, LDH, CK, cTnI, α-HBDH and hs-CRP at T1∼4 were lower in the FDP group than in the NS group (P < 0.001). Compared with the NS group, the dosage of dopamine administered 1∼90min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P < 0.001, P < 0.001 and P = 0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group （median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm）(P < 0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group（50.3 [12.3] min vs 34.6 [6.9] min） (P < 0.001). CONCLUSIONS: The fructose-1, 6-bisphosphate postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation.

Anchoring PdOx clusters on defective alumina for improved catalytic methane oxidation.

Evolution of the Pd active centers in size and spatial distribution leads to an irreversible deactivation in many high-temperature catalytic processes. This research demonstrates the use of a defective alumina (Al2O3-x) as catalyst support to anchor Pd atoms and suppress the growth of Pd clusters in catalytic methane oxidation. A combination of operando spectroscopy and density functional theory (DFT) calculations provide insights into the evolution of Pd species and reveals distinct catalytic methane oxidation mechanisms on Pd single atoms, clusters, and nanoparticles (NPs). Among these Pd species, the cluster active centers are found to be the most favorable participants in methane oxidation due to their high dispersion, high content of Pd2+ oxidation state, and resistance to deactivation by carbonates, bicarbonates, and water. The Pd/Al2O3-x catalyst shows increased stability with respect to a Pd/Al2O3 counterpart during simulated aging in alternating reducing and oxidizing conditions due to stronger interactions with the support. This study demonstrates that defect engineering of non-reducible supports can constrain the evolution of active centers, which holds promising potential for widespread utilization across diverse industrial catalytic processes, including various hydrogenation and oxidation reactions.

Dietary crude protein and protein solubility manipulation enhances intestinal nitrogen absorption and mitigates reactive nitrogen emissions through gut microbiota and metabolome reprogramming in sheep.

Dietary nutrient manipulation (e.g. protein fractions) could lower the environmental footprints of ruminants, especially reactive nitrogen (N). This study investigated the impacts of dietary soluble protein (SP) levels with decreased crude protein (CP) on intestinal N absorption, hindgut N metabolism, fecal microbiota and metabolites, and their linkage with N metabolism phenotype. Thirty-two male Hu sheep, with an age of six months and an initial BW of 40.37 ± 1.18 kg, were randomly assigned to four dietary groups. The control diet (CON), aligning with NRC standards, maintained a CP content of 16.7% on a dry matter basis. Conversely, the experimental diets (LPA, LPB, and LPC) featured a 10% reduction in CP compared with CON, accompanied by SP adjustments to 21.2%, 25.9%, and 29.4% of CP, respectively. Our results showed that low-protein diets led to significant reductions in the concentrations of plasma creatinine, ammonia, urea N, and fecal total short-chain fatty acids (SCFA) (P < 0.05). Notably, LPB and LPC exhibited increased total SCFA and propionate concentrations compared with LPA (P < 0.05). The enrichment of the Prevotella genus in fecal microbiota associated with energy metabolism and amino acid (AA) biosynthesis pathways was evident with SP levels in low-protein diets of approximately 25% to 30%. Moreover, LPB and LPC diets demonstrated a decrease in fecal NH 4 + -N and NO 2 - -N contents as well as urease activity, compared with CON (P < 0.05). Concomitantly, reductions in fecal glutamic acid dehydrogenase gene (gdh), nitrite reductase gene (nirS), and nitric oxide reductase gene (norB) abundances were observed (P < 0.05), pointing towards a potential reduction in reactive N production at the source. Of significance, the up-regulation of mRNA abundance of AA and peptide transporters in the small intestine (duodenum, jejunum, and ileum) and the elevated concentration of plasma AA (e.g. arginine, methionine, aspartate, glutamate, etc.) underscored the enhancement of N absorption and N efficiency. In summary, a 10% reduction in CP, coupled with an SP level of approximately 25% to 30%, demonstrated the potential to curtail reactive N emissions through fecal Prevotella enrichment and improve intestinal energy and N utilization efficiency.

Corrigendum: Comparison of "Huaxi-1" or "histidine-tryptophan-ketoglutarate" cardioplegia in an animal model.

[This corrects the article DOI: 10.3389/fcvm.2024.1385253.].

ScLNet: A cornea with scleral lens OCT layers segmentation dataset and new multi-task model.

Objective: To develop deep learning methods with high accuracy for segmenting irregular corneas and detecting the tear fluid reservoir (TFR) boundary under the scleral lens. Additionally, this study aims to provide a publicly available cornea with scleral lens OCT dataset, including manually labeled layer masks for training and validation of segmentation algorithms. This study introduces ScLNet, a dataset comprising cornea with Scleral Lens (ScL) optical coherence tomography (OCT) images with layer annotations, and a multi-task network designed to achieve rapid, accurate, automated segmentation of scleral lens with regular and irregular corneas. Methods: We created a dataset comprising 31,360 OCT images with scleral lens annotations. The network architecture includes an encoder with multi-scale input and a context coding layer, along with two decoders for specific tasks. The primary task focuses on predicting ScL, TFR, and cornea regions, while the auxiliary task, aimed at predicting the boundaries of ScL, TFR, and cornea, enhances feature extraction for the main task. Segmentation results were compared with state-of-the-art methods and evaluated using Dice similarity coefficient (DSC), intersection over union (IoU), Matthews correlation coefficient (MCC), Precision, and Hausdorff distance (HD). Results: ScLNet achieves 98.22 % DSC, 96.50 % IoU, 98.13 % MCC, 98.35 % Precision, and 3.6840 HD (in pixels) in segmenting ScL; 97.78 % DSC, 95.66 % IoU, 97.71 % MCC, 97.70 % Precision, and 3.7838 HD (in pixels) in segmenting TFR; and 99.22 % DSC, 98.45 % IoU, 99.15 % MCC, 99.14 % Precision, and 3.5355 HD (in pixels) in segmenting cornea. The layer interfaces recognized by ScLNet closely align with expert annotations, as evidenced by high IoU scores. Boundary metrics further confirm its effectiveness. Conclusion: We constructed a dataset of corneal OCT images with ScL wearing, which includes regular and irregular cornea patients. The proposed ScLNet achieves high accuracy in extracting ScL, TFR, and corneal layer masks and boundaries from OCT images of the dataset.

Predictive Value of Pretreatment Neutrophil to Albumin Ratio in Response to Neoadjuvant Chemotherapy of Breast Cancer.

Background: The immune system appears to play a crucial role in how breast cancer responds to chemotherapy. In this study, we investigated a peripheral marker of immune and inflammation named the neutrophil to albumin ratio (NAR) to explore its potential relationship with pathological complete response (pCR) in locally advanced breast cancer patients who underwent neoadjuvant chemotherapy (NAC). Methods: We conducted a retrospective analysis of 212 consecutive breast cancer patients who received NAC. The NAR was calculated by examining the complete blood cell count and albumin level in peripheral blood before starting NAC. Through ROC curve analysis, we determined the optimal cutoff value for NAR as 0.0877. We used Pearson's chi-square test or Fisher's exact test to evaluate the relationship between NAR and pCR, as well as other clinical and pathological characteristics. Logistic regression models were employed for univariate and multivariate analyses. Results: The results of both univariate and multivariate logistic regression analyses showed that NAR was associated with tumor pathological regression. The NAR high group had a higher pCR rate compared to the NAR low group (OR 3.127 [95% CI 1.545-6.328]; p = 0.002). Conclusion: According to this study, it was observed that patients with breast cancer who had high levels of NAR were more likely to achieve pCR when undergoing NAC.

Genomic analysis of Alteromonas sp. M12 isolated from the Mariana Trench reveals its role in dimethylsulfoniopropionate cycling.

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in stress tolerance, global carbon and sulfur cycling, and chemotaxis. It is the main precursor of the climate active gas dimethyl sulfide (DMS), which is the greatest natural source of bio­sulfur transferred from ocean to atmosphere. Alteromonas sp. M12, a Gram-negative and aerobic bacterium, was isolated from the seawater samples collected from the Mariana Trench at the depth of 2500 m. Here, we report the complete genome sequence of strain M12 and its genomic characteristics to import and utilize DMSP. The genome of strain M12 contains one circular chromosome (5,012,782 bp) with the GC content of 40.88%. Alteromonas sp. M12 can grow with DMSP as a sole carbon source, and produced DMS with DMSP as a precursor. Genomic analysis showed that strain M12 contained a set of genes involved in the downstream steps of DMSP cleavage, but no known genes encoding DMSP transporters or DMSP lyases. The results indicated that this strain contained novel DMSP transport and cleavage genes in its genome which warrants further investigation. The import of DMSP into cells may be a strategy of strain M12 to adapt the hydrostatic pressure environment in the Mariana Trench, as DMSP can be used as a hydrostatic pressure protectant. This study sheds light on the catabolism of DMSP by deep-sea bacteria.

Exploring the role of pyroptosis and immune infiltration in sepsis based on bioinformatic analysis.

PURPOSE: Sepsis is a disease that is typically treated in intensive care units with high mortality and morbidity. Pyroptosis is a newly identified type of programmed cell death and is characterized by inflammatory cytokine secretion. However, the role of pyroptosis in sepsis remains unclear. METHODS: GSE28750 and GSE134347 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed pyroptosis genes (DEPGs) were identified between sepsis and healthy controls. Machine learning was used to further narrow the gene range. Receiver operating curves (ROC) were generated to estimate the diagnostic efficacy. Immune infiltration levels were estimated via single-sample gene set enrichment analysis (ssGSEA). A network database was used to predict the upstream transcription factors and miRNAs of DEPGs. Finally, the expression of the genes was validated by qRT-PCR between sepsis patients and healthy controls. RESULTS: We found that the pyroptosis pathway was enriched and activated in sepsis. 8 DEPGs were identified. A heatmap showed that the genes, NLRC4, NAIP, IL-18, AIM2 and ELANE, were abundant in the sepsis samples, and the genes, NLRP1, CHMP7 and TP53, were abundant in the healthy control samples. The ssGSEA results showed that the abundances of activated dendritic cells, MDSC, macrophage, plasmacytoid dendritic cells, regulatory T-cells, and Th17-cells were significantly higher, while the activated B-cell, activated CD8 T-cell, CD56 dim tural killer cell, immature B-cell, monocyte, and T follicular helper cell abundances were lower in sepsis samples compared to healthy controls. The qRT-PCR results showed that the expression levels of NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1 were consistant with the bioinformatic analyses, while the expression level of AIM2 has no significant difference. CONCLUSION: Our study identified seven potential pyroptosis-related genes, NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1. This study revealed that pyroptosis may promote sepsis development by activating the immune response.

Identification of immune-inflammation targets for intracranial aneurysms: A multiomics and epigenome-wide study integrating summary-data-based mendelian randomization, single-cell-type expression analysis, and DNA methylation regulation.

BACKGROUND: Dysfunction of the immune system and inflammation plays a vital role in developing intracranial aneurysms (IAs). However, the progress of genetic pathophysiology is complicated and not entirely elaborated. This study aimed to explore the genetic associations of immune- and inflammation-related genes (IIRGs) with IAs and their subtypes using Mendelian randomization, colocalization test, and integrated multiomics functional analysis. METHODS: We conducted a summary-data-based Mendelian randomization (SMR) analysis using data from several genome-wide association studies of gene expression (31,684 European individuals) and protein quantitative trait loci (35,559 Icelanders), as well as information on IAs and their subtypes from The International Stroke Genetics Consortium (IGSC) for discovery phase and the FinnGen study for replication. This analysis aimed to determine the causal relationship between IIRGs and the risk of IAs and their subtypes. Further functional analyses, including DNA methylation regulation (1980, European individuals), single-cell-type expression analysis, and protein-protein interaction, were conducted to detect the specific cell type with enriched expression and discover potential drug targets. RESULTS: After integrating multi-omics evidence from expression quantitative trait loci (eQTL)and protein quantitative trait loci(pQTL), we found that tier 1: RELT [odds ratio (OR): 0.14, 95% confidence interval (CI): 0.04-0.50], TNFSF12 (OR: 1.24, 95% CI: 1.24-1.43), tier 3:ICAM5 (OR: 0.89, 95% CI: 0.82-0.96), and ERAP2 (OR: 1.07, 95% CI: 1.02-1.12) were associated with the risk of IAs; tier 3: RELT (OR: 0.11, 95% CI: 0.02-0.54), ERAP2 (OR: 1.08, 95% CI: 1.02-1.13), and TNFSF12 (OR: 1.24, 95% CI: 1.05-1.47) were associated with the risk of aneurysmal subarachnoid hemorrhage (aSAH); and tier 1:RELT (OR: 0.04, 95% CI: 0.01-0.30) was associated with the risk of unruptured intracranial aneurysms (uIAs). Further functional analyses showed that RELT was regulated by cg06382664 and cg18850434 and ICAM5 was regulated by cg04295144 in IAs; RELT was regulated by cg06382664, cg08770935, cg16533363, and cg18850434 in aSAH; and RELT was regulated by cg06382664 and cg21810604 in uIAs. In addition, we found that H6PD (OR: 1.13, 95% CI: 1.01-1.28), NT5M (OR: 1.91, 95% CI: 1.21-3.01), and NPTXR (OR: 1.13, 95% CI: 1.01-1.26) were associated with IAs; NT5M (OR: 2.13, 95% CI: 1.23-3.66) was associated aSAH; and AP4M1 (OR: 0.06, 95% CI: 0.01-0.42) and STX7 (OR: 3.97, 95% CI: 1.41-11.18) were related to uIAs. STX7 and TNFSF12 were mainly enriched in microglial cells, whereas H6PD, STX7, and TNFSF12 were mainly enriched in astrocytes. CONCLUSIONS: After integrating multi-omics evidence, we eventually identified IIRGs: RELT, TNFSF12, ICAM5 and ERAP2 were the novel therapy targets for IAs. These new results confirmed a vital role of immune and inflammation in the etiology of IAs, contributing to enhance our understanding of the immune and inflammatory mechanisms in the pathogenesis of IAs and revealing the complex genetic causality of IAs.

Compounds derived from 5-fluoropyridine and benzo[b]thiophene: killing Mycobacterium tuberculosis and reducing its virulence.

The rise of drug-resistant Mycobacterium tuberculosis (Mtb) has extended the duration of tuberculosis (TB) treatment and reduced the likelihood of cure. One strategy to combat this issue is the development of inhibitors targeting the virulence factors of bacterial pathogens. Mtb' catalase (KatG) is crucial for its detoxification mechanisms and also serves as a significant virulence factor for the bacterium. In this study, twelve derivatives synthesized from 5-fluoropyridine and benzo[b]thiophene demonstrated antimycobacterial efficacy with minimum inhibitory concentrations (MICs) varying between 0.5 and 32 µg/mL. Compound 2, 2-(benzo[b]thiophene-2-ylmethylene) hydrazine-1-carbothioamide, emerged as the most potent candidate. It effectively inhibited Mtb KatG. Molecular docking revealed that compound 2 binds  to the active site of Mtb-KatG with  docking score of 114. The rabbit skin tuberculosis model was employed to assess the virulence of Mtb. Animal study results indicated that the granulomas induced by Mtb after treatment with compound 2 were reduced in size, exhibited a lower bacterial load, and the bacteria were no longer aggregated, in contrast to those caused by untreated Mtb. Hence, compound 2 can be regarded as a molecule capable of neutralizing the virulence factors of Mtb. This research offers insights into the design of anti-Mtb molecules with novel mechanisms of action.

Transcriptomic and Metabolomic Analyses of Soybean Protein Isolate on Monascus Pigments and Monacolin K Production.

Monascus pigments (MPs) and monacolin K (MK) are important secondary metabolites produced by Monascus spp. This study aimed to investigate the effect of soybean protein isolate (SPI) on the biosynthesis of MPs and MK based on the analysis of physiological indicators, transcriptomes, and metabolomes. The results indicated that the growth, yellow MPs, and MK production of Monascus pilosus MS-1 were significantly enhanced by SPI, which were 8.20, 8.01, and 1.91 times higher than that of the control, respectively. The utilization of a nitrogen source, protease activity, the production and utilization of soluble protein, polypeptides, and free amino acids were also promoted by SPI. The transcriptomic analysis revealed that the genes mokA, mokB, mokC, mokD, mokE, mokI, and mokH which are involved in MK biosynthesis were significantly up-regulated by SPI. Moreover, the glycolysis/gluconeogenesis, pyruvate metabolism, fatty acid degradation, tricarboxylic acid (TCA) cycle, and amino acid metabolism were effectively up-regulated by SPI. The metabolomic analysis indicated that metabolisms of amino acid, lipid, pyruvate, TCA cycle, glycolysis/gluconeogenesis, starch and sucrose, and pentose phosphate pathway were significantly disturbed by SPI. Thus, MPs and MK production promoted by SPI were mainly attributed to the increased biomass, up-regulated gene expression level, and more precursors and energies.

Silicone oil migrating into the conjunctival space and orbit after surgery for an eye-penetrating injury: A case report.

BACKGROUND: We report a case of eye-penetrating injury in which a massive silicone oil migration into the patient's subconjunctival space and orbit occurred after vitrectomy. CASE SUMMARY: A 30-year-old male patient sought medical attention at Ganzhou People's Hospital after experiencing pain and vision loss in his left eye due to a nail wound on December 9, 2023. Diagnosis of penetrating injury caused by magnetic foreign body retention in the left eye and hospitalization for treatment. On December 9, 2023, pars plana vitrectomy was performed on the left eye for intraocular foreign body removal, abnormal crystal extraction, retinal photocoagulation. Owing to the discovery of retinal detachment at the posterior pole during surgery, silicone oil was injected to fill the vitreous body, following which upper conjunctival bubble-like swelling was observed. Postoperative orbital computed tomography (CT) review indicated migration of silicone oil to the subconjunctival space and orbit through a self-permeable outlet. On December 18, 2023, the patient sought treatment at the First Affiliated Hospital of Nanchang University, China. The patient presented with a pronounced foreign body sensation following left eye surgery. On December 20, 2023, the foreign body was removed from the left eye frame and an intraocular examination was conducted. The posterior scleral tear had closed, leading to termination of the surgical procedure following supplementary laser treatment around the tear. The patient reported a significant reduction in ocular surface symptoms just one day after surgery. Furthermore, a notable decrease in the migration of silicone oil was observed in orbital CT scans. CONCLUSION: The timing of silicone oil injection for an eye-penetrating injury should be carefully evaluated to avoid the possibility of silicone oil migration.

Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.