Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM: To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS: One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P < 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS: Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P < 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION: Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.

First identified Toxoplasma gondii Type I in market-sold ducks in Fujian province, China: a significant for public health.

Toxoplasma gondii (T. gondii) is an intracellular protozoan that can cause toxoplasmosis in all warm-blooded hosts. This study focused on the prevalence and genetic characterize of T. gondii in ducks from Fujian province, China. Genomic DNA was extracted from duck tissue samples (heart, liver, lung, and muscle). To assess the genetic diversity of the T. gondii isolates, it was determined by using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. A total of 586 ducks from 5 cities in Fujian province were tested, and 35 (6.0%) of which were found to be positive for the T. gondii B1 gene. Further genotyping of these positive samples at 10 genetic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using PCR-RFLP revealed that one tissue samples (heart samples from Fuzhou ducks) were identified as Type I (ToxoDB#10). This study is the first report on the prevalence and genetic characterization of T. gondii in ducks in Fujian province, and Type I (ToxoDB#10) is found in ducks in China for the first time. The findings document the genetic characterization of T. gondii in free-range ducks from Fujian Province, thereby enriching the understanding of T. gondii genetic diversity in China. Moreover, these results provide essential data support for further prospective studies and underscores the "One Health" concept, emphasizing the integral link among human, animal, and environmental health.

Ruyi Zhenbao Tablet and Baimai Ointment Therapy in Acute Ischemic Stroke: A Study Protocol for a Multi-Center, Randomized, Double-blinded, and Parallel-Controlled Trial.

Introduction: Stroke is characterized by high incidence, recurrence rate, and mortality. Patients with acute ischemic stroke (AIS) who are ineligible for acute revascularization therapy require more effective medication treatments. A previous clinical study showed that Ruyi Zhenbao tablets and Baimai ointments might be effective against AIS; however, high-quality clinical evidence supporting their application in AIS is lacking. To explore the efficacy of the two classic Tibetan medicines in the treatment of AIS, a randomized clinical trial will be conducted in patients with AIS who are not eligible for thrombolytic treatment. Methods: A prospective, randomized, multiple-center, double-blinded, placebo-controlled, and parallel-group trial will be conducted. We shall randomize 480 eligible participants to either the intervention or the control group. The distribution ratio of each group will be 1:1:1:1, including 120 patients each in the dual-medication group, the Baimai ointment group, the Ruyi Zhenbao tablet group, and the placebo group. Participants will be treated with medication for 8 weeks, and they will receive three follow-up visits: at 4 weeks (D29), 8 weeks (D56), and 90 days (D90) after commencing treatment. The primary outcome will be D90 change in the simplified Fugl-Meyer score from baseline to posttreatment. The secondary outcomes are as follows: D29 change of simplified Fugl-Meyer score from baseline to posttreatment; proportion of participants whose D29 NIHSS scores decreased by four or more points from baseline D90 proportion of subjects with mRS score of 0-2 (inclusive); D90 proportion of subjects with Barthel index score ≥95; D90 incidence of cardiovascular and cerebrovascular events. Safety endpoint includes mortality within 90 days; proportion of subjects with adverse events/serious adverse events within 90 days. Conclusion: This research protocol lays a solid groundwork for its practical execution. This study is poised to serve as a reference for other Tibetan medicine researchers, contributing to the reduction of stroke-related expenditures globally and, in turn, benefiting a broader population of stroke patients.

Genome-wide identified VvOFP genes family and VvOFP4 functional characterization provide insight into fruit shape in grape.

Ovate Family Proteins (OFPs) are emerging as novel transcriptional regulators of fruit shape. Despite their established role in various species, their involvement in regulating grape fruit shape remains understudied. This study encompassed a comprehensive evaluation of 16 grape OFP genes in total at the whole genome level. Phylogenetic and synteny analyses established a close relationship between grape VvOFP genes and their tomato counterparts. Expression profiling post-treatment with gibberellic acid (GA3) and thidiazuron (TDZ) revealed that certain OFP genes responded to these regulators, with VvOFP4 showing peak expression three days post-anthesis. Functional assays via overexpression of VvOFP4 in tobacco and tomato altered the morphology of both vegetative and reproductive organs, including leaves, stamens, and fruits/pods. Paraffin sections of transgenic tobacco stems and tomato fruits demonstrated that VvOFP4 overexpression modifies cell dimensions, leading to changes in organ morphology. Additionally, treatments with GA3 and TDZ similarly influenced the shape of grape pulp cells and thereby the overall fruit morphology. These findings suggest that the VvOFP4 gene plays a crucial role in fruit shape determination by modulating cell shape and presents a potential target for future grape breeding programs aimed at diversifying fruit shapes.

Nicotinamide N-Methyltransferase (NNMT) is Involved in Gastric Adenocarcinoma Immune Infiltration by Driving Amino Acid Metabolism.

Objectives: This study investigates the role of Nicotinamide N-methyltransferase (NNMT) in immune infiltration modulation through amino acid metabolism in gastric adenocarcinoma (STAD). Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and validated with clinical samples, we analyzed NNMT expression and its prognostic implications in STAD. Differential amino acid profiles between cancerous and adjacent normal tissues were assessed, along with their associations with NNMT. Results: NNMT exhibits heightened expression in STAD cancer tissues, positively correlating with tumor immune infiltration. Additionally, twenty-eight amino acids display differential expression in gastric tissue, with their metabolic enzymes showing connections to NNMT. Conclusions: Elevated NNMT expression in STAD tissues potentially influences amino acid metabolism, thereby affecting immune infiltration dynamics and tumorigenesis in gastric adenocarcinoma.

Sustainability of exercise-induced benefits on circulating MicroRNAs and physical fitness in community-dwelling older adults: a randomized controlled trial with follow up.

BACKGROUND: Circulating miRNAs (c-miR) have been shown to be potential biomarkers in sarcopenia, but the miRNAs response to aerobic exercise in older people remains inconclusive. We sought to examine the exercise benefits on physical fitness and miRNAs, and to explore the mediating effect of miRNAs on training-induced fitness changes. METHODS: This controlled trial recruited 58 community-dwelling older adults and randomized them into exercise group (EX) and control group (CON). EX received 8-week supervised moderate intensity cycling training 3x/week. C-miR expression (c-miR-21, c-miR-126, c-miR-146a, c-miR-222), physical fitness (body composition, cardiorespiratory fitness, muscular fitness) and physical activity level (PAL, measured as in daily step counts) were evaluated at baseline, post-training, and post-16-week follow-up. The mediating effect of miRNA expression onto exercise-induced physical fitness change was determined by causal mediation analysis (CMA). RESULTS: Exercise significantly improved body fat and cardiorespiratory fitness in older people while maintaining muscle mass and strength, and augmented expression of c-miR-126, c-miR-146a, and c-miR-222 for up to 16 weeks post-training. Notably, older people in EX had substantially higher daily step counts than CON throughout the study even after the active training period. However, CMA revealed no significant indirect effect but a potential mediating effect of c-miR-21, but not the rest, onto the body composition, cardiorespiratory fitness, and lower limb strength. CONCLUSION: An eight-week supervised MICT program promoted a higher level of physical activity up to 16 weeks post-training, which induces better cardiorespiratory fitness and resists decline in muscular measures. C-miRNA, especially c-miR-21, potentially mediates the training effect upon fitness.

Comprehensive Analysis of Chemical Ingredients of Waiganfengsha Granule and Absorbed Components in Rat Plasma Based on UHPLC-Q-TOF-MS.

OBJECTIVE: Waiganfengsha Granule, an over-the-counter drug, is commonly used for treating windheat cold and sore throat in clinical settings. However, its material basis of medicinal efficacy is still unclear. In this study, an efficient integrated analytical strategy was established for its chemical and metabolite profiles study. METHODS: Firstly, to avoid the possible false-positive results of structural elucidation, an in-house component library that contains chemical constituents reported in the literature from the six individual medicines of Waiganfengsha Granule was established. Secondary, mass data post-processing techniques, including precursor ion list and neutral loss filtering, were applied to enhance the identification accuracy. Thirdly, for the rapid characterization of those absorbed components after oral administration in rats, the identified chemical constituents were used as candidate components for the serum analysis. By comparing the retention time and analyzing mass data, the metabolites in rat plasma were identified. RESULTS: As a result, 57 chemical ingredients were identified, including 21 phenolic acids, 9 alkaloids, 2 flavonoids, 5 lignins, 13 saponins, and 7 other compounds. Among these, 12 compounds were unambiguously identified by comparison with reference standards, and 45 were tentatively characterized by analyzing their accurate MS data, MS/MS fragmentation patterns, and also by comparison with those data reported in the literature. Additionally, 46 metabolites were detected and identified in rat plasma. CONCLUSION: This study is beneficial for understanding the chemical composition and metabolic profiles of Waiganfengsha Granule, and the results obtained might provide a solid basis for further studies on its functional mechanism.

Identification of Vernonia patula Merr. and Its Similar Varieties Based on a Combination of HPLC Fingerprinting and Chemical Pattern Recognition.

Vernonia patula Merr. (VP) is a traditional medicine used by the Zhuang and Yao people, known for its therapeutic properties in treating anemopyretic cold and other diseases. Distinguishing VP from similar varieties such as Praxelis clematidea (PC), Ageratum conyzoides L. (AC) and Ageratum houstonianum Mill (AH) was challenging due to their similar traits and plant morphology. The HPLC fingerprints of 40 batches of VP and three similar varieties were established. SPSS 20.0 and SIMCA-P 13.0 were used to statistically analyze the chromatographic peak areas of 37 components. The results showed that the similarity of the HPLC fingerprints for each of the four varieties was >0.9, while the similarity between the control chromatogram of VP and its similar varieties was <0.678. Cluster analysis and partial least squares discriminant analysis provided consistent results, indicating that all four varieties could be individually clustered together. Through further analysis, we found isochlorogenic acid A and isochlorogenic acid C were present only in the original VP, while preconene II was present in the three similar varieties of VP. These three components are expected to be identification points for accurately distinguishing VP from PC, AC and AH.

Synergistic suppression of BDNF via epigenetic mechanism deteriorating learning and memory impairment caused by Mn and Pb co-exposure.

Microglia, the resident immune cells of the central nervous system (CNS), play a dual role in neurotoxicity by releasing the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF) in response to environmental stress. Suppression of BDNF is implicated in learning and memory impairment induced by exposure to manganese (Mn) or lead (Pb) individually. Methyl CpG Binding Protein 2 (MeCp2) and its phosphorylation status are related to BDNF suppression. Protein phosphatase2A (PP2A), a member of the serine/threonine phosphatases family, dephosphorylates substrates based on the methylation state of its catalytic C subunit (PP2Ac). However, the specific impairment patterns and molecular mechanisms resulting from co-exposure to Mn and Pb remain unclear. Therefore, the purpose of this study was to explore the effects of Mn and Pb exposure, alone and in combination, on inducing neurotoxicity in the hippocampus of mice and BV2 cells, and to determine whether simultaneous exposure to both metals exacerbate their toxicity. Our findings reveal that co-exposure to Mn and Pb leads to severe learning and memory impairment in mice, which correlates with the accumulation of metals in the hippocampus and synergistic suppression of BDNF. This suppression is accompanied by up-regulation of the epigenetic repressor MeCp2 and its phosphorylation status, as well as demethylation of PP2Ac. Furthermore, inhibition of PP2Ac demethylation using ABL127, an inhibitor for its protein phosphatase methylesterase1 (PME1), or knockdown of MeCp2 via siRNA transfection in vitro effectively increases BDNF expression and mitigates BV2 cell damage induced by Mn and Pb co-exposure. We also observe abnormal activation of microglia characterized by enhanced release of the NLRP3 inflammasome, Casepase-1 and pro-inflammatory cytokines IL-1ß, in the hippocampus of mice and BV2 cells. In summary, our experiments demonstrate that simultaneous exposure to Mn and Pb results in more severe hippocampus-dependent learning and memory impairment, which is attributed to epigenetic suppression of BDNF mediated by PP2A regulation.

The relationship between human blood metabolites and preeclampsia-eclampsia: A Mendelian randomization study.

Preeclampsia and eclampsia are serious complications of pregnancy, leading to high rates of maternal and neonatal mortality. During pregnancy, there are changes in relevant serum metabolites in women. However, it remains unclear if these serum metabolites contribute to the development of associated disorders during pregnancy. Therefore, we conducted a Mendelian randomization study to explore the causal relationship between serum metabolites and preeclampsia and eclampsia. We utilized the inverse variance weighted model as our primary analysis approach. We complemented this with sensitivity analyses, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis, to ensure the robustness of our findings. Furthermore, we conducted linkage disequilibrium score regression, multivariable Mendelian randomization, and metabolic pathway analysis to further explore the genetic data. The Mendelian randomization analysis has identified γ-glutamylglutamine, inosine, and isoleucine 10 metabolites that are significantly associated with preeclampsia, and γ-glutamylglutamine and phenylacetate 8 metabolites that may potentially contribute to the development of eclampsia. Notably, γ-glutamylglutamine has been found to have a causal relationship with both preeclampsia and eclampsia. In the multivariable Mendelian randomization analysis, our research findings suggest that both isoleucine and X-14304-leucylalanine directly impact preeclampsia within the context of amino acids and peptides. Moreover, our observations reveal that carbohydrates can also have a direct effect on preeclampsia. Importantly, it should be emphasized that only 3-lactate in amino acids has been shown to have a direct influence on eclampsia. This research has the potential to enhance our understanding of the biological variances related to disease status, providing a foundation for future investigations.

The predictive role of early inflammation and oxidative stress and the dynamics of cytokines networks in post-stroke depression.

BACKGROUNDS: Chronic inflammation and oxidative stress play an important role in the pathogenesis of PSD. The main purposes of this study were to examine the dynamic changes of cytokines networks in PSD and the predictive role of early inflammation and oxidative stress for 2-week PSD. METHODS: Patients with ischemic stroke were recruited on day 3, and those with Hamilton Depression Rating Scale 24-Item (HAMD-24) ≥8 were classified as ischemic stroke patients with depressive symptoms and others as ischemic stroke patients without depressive symptoms. Subjects were then followed up at 2 weeks and 3 months, with those meeting diagnostic criteria for depressive symptoms on the HAMD ≥8 and the Statistical Manual of Mental Disorders-V (DSM-V) as the PSD group, and the others as the non-PSD group. RESULTS: At 3 days, IFN-γ, IL-12(p70), IL-12(p40), IL-2, IL-28A/IFNλ2, and IL-19 were elevated in ischemic stroke patients with depressive symptoms. At 2 weeks, IL-12(p40), IL-19, IL-22, IFN-ß and MMP-1 all were increased in PSD patients. At 3 months, IL-2, IFN-ß and sCD163 increased in PSD group. Longitudinally, the inflammatory response decreased significantly in PSD group from 2 weeks to 3 months of follow-up, while it gradually decreased in non-PSD group from 3 days to 3 months of follow-up. SOD was positively related to IL-12(p70), IFN-γ and IL-20. Plasma IFN-γ at 3 days may be a potential predictive biomarker for 2-week PSD. CONCLUSIONS: Peripheral inflammation and oxidative stress are involved in the pathogenesis of PSD, providing new insights for its diagnosis and treatment.

The mediating role of childhood maltreatment in the association between residence migration and adolescent depression.

BACKGROUND: It is well established that residence migration can negatively affect the mental health of adolescents. However, the related factors that mediate the association between residence migration and depression are still uncertain. METHODS: The participants were 16,037 adolescents in junior middle schools. A self-administered questionnaire was used for the survey. In addition to collecting general demographic characteristics of the participants, including age, gender, local residence status, only child status, parental marriage status and parent-child relationship, the questionnaire also contained the 9-item Patient Health Questionnaire, the short form of the Childhood Trauma Questionnaire and the Connor-Davidson Resilience Scale. Data analysis was conducted using SPSS software. RESULTS: A total of 14,059 valid questionnaires were collected, resulting in 12,122 local adolescents, defined as being born and raised locally, and 1937 migrant adolescents, defined as being transferred from other regions. Meanwhile, 53.3 % of local adolescents and 58.2 % of migrant adolescents reported depressive symptoms. This result indicated that residence migration might contribute to depression symptoms(OR = 1.136, 95%CI: 1.013-1.273, p < 0.05). Childhood maltreatment and parental divorce are risk factors for depression in migrant adolescents. For all adolescents, resilience and a good parent-child relationship may reduce the risk of depression. Childhood maltreatment completely mediates residence migration-related depression(95 % bootstrap CI = 0.146, 0.323). CONCLUSION: This study revealed that residence migration could contribute to adolescent depression, and childhood maltreatment may largely mediate this process, providing new insight into the relationship between adolescent depressive symptoms and residence migration. Reducing childhood maltreatment may effectively improve the depressive symptoms of migrant adolescents.

Zn2+-Enhanced Lithium Magnesium Molybdate Ultralow Temperature Cofired Ceramics for Terahertz Wavefront Modulation Applications.

High efficiency, high frequency, low error, and low latency of wavefront modulation are challenges that must be addressed simultaneously in 5G/6G communication systems. In order to cope with these challenges, novel Li2Mg2-xZnxMo3O12 (x = 0.00-0.08) ceramics are prepared by a solid-state reaction method. The microwave dielectric properties (εr = 8.7, Q × f = 61,312 GHz, τf = -59.1 ppm/°C) and terahertz transmission properties (εr1 = 8.3, tanδ1 = 0.00908, Tamplitude = 0.673, Δphase = 27.65°) of this ceramic (x = 0.06, 625 °C) are effectively enhanced by Zn2+. The chemical compatibility between this ceramic and the Al electrode is demonstrated. The reflection amplitude of this ceramic combined with the Al electrode at 0.5 THz is revealed, and the error between simulation and experiment is only 0.06. A terahertz reflective device for wavefront modulation is designed and demonstrated by using this ceramic and Al electrode. This device can deflect the wavefront of cross-polarized waves and has a certain isolation effect on co-polarized waves. This work accelerates the development of dielectric ceramics and ultralow temperature cofired ceramics technology in the terahertz field.

First Molecular Detection and Genotype Identification of Toxoplasma gondii in Chickens from Farmers' Markets in Fujian Province, Southeastern China.

Toxoplasma gondii is an opportunistic pathogenic protozoan that can infect all nucleated cells in almost all warm-blooded animals, including humans. T. gondii infection has been reported in many food animals worldwide. However, the prevalence and genotypes of T. gondii in chickens from farmers' markets in Fujian province in southeastern China remain unreported. In the present study, four tissue samples from each of the 577 chickens (namely, the heart, liver, lungs, and muscles) were collected from farmers' markets in five regions of Fujian province (Zhangzhou, Sanming, Quanzhou, Fuzhou, and Longyan). We first analyzed the prevalence and genotypes of T. gondii using PCR targeting of the B1 gene of T. gondii. Of the 577 chickens, thirty-two (5.5%) tested positive for the B1 gene. Among the five regions, Sanming had the highest infection rate (16.8%, 16/95), followed by Quanzhou (8.0%, 8/100), Longyan (5.0%, 5/100), Zhangzhou (1.1%, 2/182), and Fuzhou (1.0%, 1/100). Among these thirty-two T. gondii-positive chickens, the infection rates of the lungs, heart, liver, and muscles were 68.8% (22/32), 34.4% (11/32), 28.1% (9/32), and 9.4% (3/32), respectively. Significant differences in prevalence were found among the different regions (χ2 = 35.164, p < 0.05) and tissues (χ2 = 25.874, p < 0.05). A total of 128 tissue and organ samples of the thirty-two T. gondii-positive chickens from the different regions were analyzed using PCR-restriction fragment length polymorphism (PCR-RFLP) on the basis of 10 genetic markers. Seven tissue samples (lung samples from five chickens, heart samples from one chicken, and liver samples from one chicken) underwent successful amplification at all the genetic markers, and all the T. gondii genotypes were identified as genotype I (ToxoDB #10). These findings serve as a foundation for evaluating the risk of T. gondii contamination in chicken products intended for human consumption and offer insight into preventing the transmission of the parasite from chickens to humans.

A preoperative prediction of lymph node metastasis in early cervical squamous cell cancer with hematologica - based model.

Background: This study aimed to construct a preoperative model predicting lymph node metastasis (LNM) in IB1-IIA2 stage cervical squamous cell cancer (CSCC) based on hematological indexes. Merhods: Between February 2011 and February 2022, 463 patients with IB1-IIA2 stage CSCC underwent radical resection. Patients were allocated to either a model-development cohort (n=337) or a validation cohort (n=126). The final model was determined by comparing different methods of variable selection, and then its discrimination and calibration metrics were evaluated. A predicted probability of LNM < 5% was defined as low risk. ROC curves were used to define high risk. Results: Age, lactate dehydrogenase level, FIGO stage, squamous cell carcinoma antigen, cancer antigen 125, and cancer antigen 199 were identified as critical factors for the construction of the model. The model demonstrated good discrimination and calibration (concordance index, 0.761; 95% confidence interval, 0.666-0.884). In the validation cohort the discrimination accuracy was 0.821 (95% confidence interval, 0.714 - 0.927). In the model-development cohort, 11.9% were classified as low risk with a negative predictive value of 95.0%, and 24.9% were classified as high risk with a positive predictive value of 39.3%. Conclusion: A predictive model was developed and validated for LNM in IB1-IIA2 stage CSCC. The model will assist physicians in appraising the risk of LNM in preoperative patients and could aid in patient counseling and individualized clinical decision-making.

RNA m5C methylation orchestrates BLCA progression via macrophage reprogramming.

Recently, epigenetics showed essential roles in tumour microenvironment (TME) and immunotherapy response, however, the functions of RNA 5-methylcytosine (m5C) modification in TME remains unknown. According to 13 m5C regulators, we evaluated 412 BLCA patients from The Cancer Genome Atlas (TCGA) database. The m5C score was constructed by unsupervised clustering analysis and principal component analysis (PCA) algorithms. Gene set variation analysis (GSVA), ESTIMATE algorithm, and immunohistochemical (IHC) staining were performed. Macrophage chemotaxis assay was used to assess the M2 macrophages. Among the 412 patients, the frequency of mutation was 13%. m5C regulators was expressed significantly in BLCA tissue compared with normal tissue. Then, two m5C methylation modification patterns were identified with dissimilar TME cell infiltration patterns. The C1 alteration pattern in the m5C cluster was connected with better survival. In addition, we found that NSUN6 was highly correlated with recruitment of macrophages via bioinformatics and IHC. Further experiment validated that NSUN6 promoted HDAC10 expression by mediating m5C methylation, inhibited the transcription of macrophage-associated chemokines and thus inhibited the recruitment of M2 macrophages. The m5C score constructed by m5C modification pattern showed that high m5C score group had a better prognosis. This study uncovered the significant roles of m5C modifications in modulating the TME and indicated that NSUN6 could inhibit the recruitment of M2 macrophages via m5C methylation, which provided novel insight into epigenetic regulation of TME and clinical suggestions for immunotherapeutic strategies.

Micro-mechanism insights into the adsorption of anionic dyes using quaternary ammonium-functionalised chitosan aerogels.

The development of adsorbents with outstanding adsorption capacities, wide versatility, and excellent recyclability for the removal of organic dyes remains a challenge. In this study, a quaternised chitosan-based aerogel (QCSA) was fabricated via a facile method to effectively treat concomitant anionic dyes. Porous QCSA with high hydrophilicity, nontoxicity, excellent thermal stability, and sustainability exhibits adsorption properties superior to most previously reported adsorbents. The equilibrium adsorption capacities for Congo red, Sunset yellow, and Methyl orange were 1259.6, 550.2, and 607.5 mg/g, respectively. Notably, the spent QCSA exhibits excellent cyclic performance. The multilayer adsorption, external-internal mass transfer resistance, and adsorption on the active site models were employed to enable a more accurate description of the dynamic characteristics, confirming that double-layer chemisorption was the dominant process. A quantitative analysis of the electrostatic potential and the independent gradient model further verified that electrostatic interactions, hydrogen bonding, and van der Waals forces led to the highly efficient adsorption of dye molecules. Therefore, the eco-friendly and recyclable QCSA is a promising adsorbent for trapping anionic dyes from aquatic systems.

Genome-Scale Analysis of the Grapevine KCS Genes Reveals Its Potential Role in Male Sterility.

Very long-chain fatty acid (VLCFA) synthesis in plants, is primarily rate-limited by the enzyme 3-ketoacyl CoA synthase (KCS), which also controls the rate and carbon chain length of VLCFA synthesis. Disruption of VLCFA during pollen development, may affect the pollen wall formation and ultimately lead to male sterility. Our study identified 24 grapevine KCS (VvKCS) genes and provided new names based on their relative chromosome distribution. Based on sequence alignment and phylogenetic investigation, these genes were grouped into seven subgroups, members of the same subgroup having similar motif structures. Synteny analysis of VvKCS genes, showed that the segmental duplication events played an important role in expanding this gene family. Expression profiles obtained from the transcriptome data showed different expression patterns of VvKCS genes in different tissues. Comparison of transcriptome and RT-qPCR data of the male sterile grape 'Y-14' and its fertile parent 'Shine Muscat', revealed that 10 VvKCS genes were significantly differentially expressed at the meiosis stage, which is a critical period of pollen wall formation. Further, joint analysis by weighted gene co-expression network analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed that five of these VvKCS (VvKCS6/15/19/20/24) genes were involved in the fatty acid elongation pathway, which may ultimately affect the structural integrity of the pollen wall in 'Y-14'. This systematic analysis provided a foundation for further functional characterization of VvKCS genes, with the aim of grapevine precision breeding improvement.

Sensitive detection of noradrenaline in human whole blood based on Au nanoparticles embedded vertically-ordered silica nanochannels modified pre-activated glassy carbon electrodes.

Sensitive determination of noradrenaline (NE), the pain-related neurotransmitters and hormone, in complex whole blood is of great significance. In this work, an electrochemical sensor was simply constructed on the pre-activated glassy carbon electrode (p-GCE) modified with vertically-ordered silica nanochannels thin film bearing amine groups (NH2-VMSF) and in-situ deposited Au nanoparticles (AuNPs). The simple and green electrochemical polarization was employed to pre-activate GCE to realize the stable binding of NH2-VMSF on the surface of electrode without the use of any adhesive layer. NH2-VMSF was conveniently and rapidly grown on p-GCE by electrochemically assisted self-assembly (EASA). With amine group as the anchor sites, AuNPs were in-situ electrochemically deposited on the nanochannels to improve the electrochemical signals of NE. Owing to signal amplification from gold nanoparticles, the fabricated AuNPs@NH2-VMSF/p-GCE sensor can achieve electrochemical detection of NE ranged from 50 nM to 2 µM and from 2 µM to 50 µM with a low limit of detection (LOD) of 10 nM. The constructed sensor exhibited high selectivity and can be easily regenerated and reused. Owing to the anti-fouling ability of nanochannel array, direct electroanalysis of NE in human whole blood was also realized.

Adipose-derived mesenchymal stem cells secrete extracellular vesicles: A potential cell-free therapy for canine renal ischaemia-reperfusion injury.

BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) and their extracellular vesicles (EVs) are a promising source of therapies for ischaemia-reperfusion (IR) because of their potent anti-inflammatory and immunomodulatory properties. OBJECTIVES: The aims of this study were to explore the therapeutic efficacy and potential mechanism of ADMSC-EVs in canine renal IR injury. METHODS: Mesenchymal stem cells (MSCs) and EVs were isolated and characterised for surface markers. A canine IR model administered with ADMSC-EVs was used to evaluate therapeutic effects on inflammation, oxidative stress, mitochondrial damage and apoptosis. RESULTS: CD105, CD90 and beta integrin ITGB were positively expressed in MSCs, while CD63, CD9 and intramembrane marker TSG101 were positively expressed in EVs. Compared with the IR model group, there was less mitochondrial damage and reduction in quantity of mitochondria in the EV treatment group. Renal IR injury led to severe histopathological lesions and significant increases in biomarkers of renal function, inflammation and apoptosis, which were attenuated by the administration of ADMSC-EVs. CONCLUSIONS: Secretion of EVs by ADMSCs exhibited therapeutic potential in renal IR injury and may lead to a cell-free therapy for canine renal IR injury. These findings revealed that canine ADMSC-EVs potently attenuate renal IR injury-induced renal dysfunction, inflammation and apoptosis, possibly by reducing mitochondrial damage.