Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China (ANGEL-REBOOT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: Unsuccessful recanalisation or reocclusion after thrombectomy is associated with poor outcomes in patients with large vessel occlusion (LVO) acute ischaemic stroke (LVO-AIS). Bailout angioplasty or stenting (BAOS) could represent a promising treatment for these patients. We conducted a randomised controlled trial with the aim to investigate the safety and efficacy of BAOS following thrombectomy in patients with LVO. METHODS: ANGEL-REBOOT was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, blinded-endpoint clinical trial conducted at 36 tertiary hospitals in 19 provinces in China. Participants with LVO-AIS 24 h after symptom onset were eligible if they had unsuccessful recanalisation (expanded Thrombolysis In Cerebral Infarction score of 0-2a) or risk of reocclusion (residual stenosis >70%) after thrombectomy. Eligible patients were randomly assigned by the minimisation method in a 1:1 ratio to undergo BAOS as the intervention treatment, or to receive standard therapy (continue or terminate the thrombectomy procedure) as a control group, both open-label. In both treatment groups, tirofiban could be recommended for use during and after the procedure. The primary outcome was the change in modified Rankin Scale score at 90 days, assessed in the intention-to-treat population. Safety outcomes were compared between groups. This trial was completed and registered at ClinicalTrials.gov (NCT05122286). FINDINGS: From Dec 19, 2021, to March 17, 2023, 706 patients were screened, and 348 were enrolled, with 176 assigned to the intervention group and 172 to the control group. No patients withdrew from the trial or were lost to follow-up for the primary outcome. The median age of patients was 63 years (IQR 55-69), 258 patients (74%) were male, and 90 patients (26%) were female; all participants were Chinese. After random allocation, tirofiban was administered either intra-arterially, intravenously, or both in 334 [96%] of 348 participants. No between-group differences were observed in the primary outcome (common odds ratio 0·86 [95% CI 0·59-1·24], p=0·41). Mortality was similar between the two groups (19 [11%] of 176 vs 17 [10%] of 172), but the intervention group showed a higher risk of symptomatic intracranial haemorrhage (eight [5%] of 175 vs one [1%] of 169), parenchymal haemorrhage type 2 (six [3%] of 175 vs none in the control group), and procedure-related arterial dissection (24 [14%] of 176 vs five [3%] of 172). INTERPRETATION: Among Chinese patients with unsuccessful recanalisation or who are at risk of reocclusion after thrombectomy, BAOS did not improve clinical outcome at 90 days, and incurred more complications compared with standard therapy. The off-label use of tirofiban might have affected our results and their generalisability, but our findings do not support the addition of BAOS for such patients with LVO-AIS. FUNDING: Beijing Natural Science Foundation, National Natural Science Foundation of China, National Key R&D Program Beijing Municipal Administration of Hospitals Incubating Program, Shanghai HeartCare Medical Technology, HeMo (China) Bioengineering, Sino Medical Sciences Technology.

Cobalt based bimetallic catalysts for heterogeneous electro-Fenton adapting to vary pH for HEDP and MIT degradation.

Most of the materials studied as catalysts in the electro-Fenton system are variants of iron oxide or iron hydroxide. However, iron-based catalysts often exhibit weak catalytic capabilities under neutral and alkaline conditions. In this work, we synthesized three cobalt based bimetallic oxides, Co2CuOx, Co2AlOx, and Co2NiOx, using hydrothermal method and evaluated them as catalysts for the heterogeneous electro-Fenton system to remove 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) and Methylisothiazolinone [2-methyl-4-isothiazolin-3-one] (MIT). Co2NiOx has the highest catalytic degradation activity for HEDP, and Co2CuOx has the best catalytic degradation effect for MIT. Based on characterization results of the catalysts, the reasons for the differences in the pollutant removal efficiency were analysed, and the optimal pH for the three cobalt based oxides to remove HEDP and MIT was investigated. The results showed that the optimal pH values of the three cobalt based bimetallic oxides are not only influenced by the second metal type, but also by the properties of pollutants. Therefore, suitable cobalt based catalysts can be selected based on the different properties of pollutants, or the composition of cobalt based catalysts can be adjusted to meet the different pH requirements of target wastewater. The three cobalt based bimetallic oxides exhibited good degradation of HEDP and MIT under neutral conditions, which to some extent solved the problem of narrow pH range in the practical application of the electro-Fenton process.

miRNAs in treatment-resistant depression: a systematic review.

BACKGROUND: Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of TRD has been steadily increasing, yet significant advancements in its diagnosis and treatment remain elusive despite extensive research efforts. The precise underlying pathogenic mechanisms are still not fully understood. Epigenetic mechanisms play a vital role in a wide range of diseases. In recent years, investigators have increasingly focused on the regulatory roles of miRNAs in the onset and progression of TRD. miRNAs are a class of noncoding RNA molecules that regulate the translation and degradation of their target mRNAs via interaction, making the exploration of their functions in TRD essential for elucidating their pathogenic mechanisms. METHODS AND RESULTS: A systematic search was conducted in four databases, namely PubMed, Web of Science, Cochrane Library, and Embase, focusing on studies related to treatment-resistant depression and miRNAs. The search was performed using terms individually or in combination, such as "treatment-resistant depression," "medication-resistant depression," and "miRNAs." The selected articles were reviewed and collated, covering the time period from the inception of each database to the end of February 2024. We found that miRNAs play a crucial role in the pathophysiology of TRD through three main aspects: 1) involvement in miRNA-mediated inflammatory responses (including miR-155, miR-345-5p, miR-146a, and miR-146a-5p); 2) influence on 5-HT transport processes (including miR-674,miR-708, and miR-133a); and 3) regulation of synaptic plasticity (including has-miR-335-5p,has-miR- 1292-3p, let-7b, and let-7c). Investigating the differential expression and interactions of these miRNAs could contribute to a deeper understanding of the molecular mechanisms underlying TRD. CONCLUSIONS: miRNAs might play a pivotal role in the pathogenesis of TRD. Gaining a deeper understanding of the roles and interrelations of miRNAs in TRD will contribute to elucidating disease pathogenesis and potentially provide avenues for the development of novel diagnostic and therapeutic strategies.

Efficacy and safety of mepolizumab in a Chinese population with severe asthma: a phase III, randomised, double-blind, placebo-controlled trial.

Background: In China, the prevalence of severe asthma with eosinophilic phenotype is rising, yet treatment options are limited. Mepolizumab is the first targeted biologic therapy for eosinophilic-driven disease in China. This study (clinicaltrials.gov identifier NCT03562195) evaluated efficacy and safety of mepolizumab in Chinese patients with severe asthma. Methods: The phase III, multicentre, randomised, placebo-controlled, double-blind, parallel-group study enrolled patients aged ≥12 years with severe asthma, with two or more exacerbations in the previous year, and on inhaled corticosteroids plus at least one controller medication. Following a 1-4-week run-in, patients were randomised 1:1 to mepolizumab 100 mg or placebo subcutaneously every 4 weeks for 52 weeks. The primary end-point was annualised rate of clinically significant exacerbations (CSEs) through week 52. Secondary end-points were time to first CSE, frequency of CSEs requiring hospitalisation/emergency department visits or hospitalisation over 52 weeks, mean change in St George's Respiratory Questionnaire (SGRQ) total score and pre-bronchodilator forced expiratory volume in 1 s (FEV1) at week 52; safety was evaluated. Results: The modified intention-to-treat population included 300 patients. At week 52 with mepolizumab versus placebo, annualised rate of CSEs was 65% lower (0.45 versus 1.31 events per year; rate ratio 0.35, 95% CI 0.24-0.50; p<0.001); time to first CSE longer (hazard ratio 0.38, 95% CI 0.26-0.56; p<0.001) and number of CSEs requiring hospitalisation/emergency department visit lower (rate ratio 0.30, 95% CI 0.12-0.77; p=0.012). From baseline to week 52, SGRQ score improved (p=0.001) and pre-bronchodilator FEV1 increased (p=0.006). Incidence of adverse events was similar between treatment groups. Conclusion: Mepolizumab provided clinical benefits to patients with severe asthma in China and showed a favourable benefit-risk profile.

The utilization of a data fusion approach to investigate fingerprint profiles of dark tea from China's different altitudes.

Dark tea refers to a kind of post-fermented product, and its quality and price vary owing to the distinct altitudes at which it grows. In this study, a novel method based on high performance liquid chromatography with a diode-array detector (HPLC-DAD) and an evaporative light scattering detector (HPLC-ELSD) was proposed for the classification of dark teas from distinct altitudes in China. Through implementing a strategy fusing feature-level data to construct a combined dataset, the classification performance of dark teas from distinct altitudes in China was evaluated after preprocessing. The results suggested that, through the feature fusion strategy, the identification accuracy rate increased from <70% of a single detector to 76.923%. After the implementation of preprocessing, the identification accuracy rate was further improved. Typically, the model identification accuracy rate after short-time Fourier Transform (STFT) treatment reached 92.85%, and the AUROC value was higher than 0.84, exhibiting a favorable generalization ability. This study provides a new thinking for the identification technology of dark teas from different altitudes in China.

Biodistribution and preclinical safety profile of legubicin: A novel conjugate of doxorubicin and a legumain-cleavable peptide linker.

Legubicin is a novel conjugate of doxorubicin and a legumain-cleavable peptide linker. It has been developed to ameliorate the side effects of doxorubicin. Biodistribution in tumor-bearing mice, acute tolerance, and potential systemic toxic effects in Sprague-Dawley rats and beagle dogs of legubicin were assessed. Legubicin exists mainly as a protein complex in plasma after entering the circulation. Compared with conventional doxorubicin at an equal molar dose in mice, we found higher exposure to doxorubicin in tumor (approximately 1.7-fold increase) while lower exposure in normal tissues (an ~3.26-, 3.46-, and 1.29-fold reduction in heart, kidney, and plasma, respectively) in tumor-bearing mice after intravenous injection of legubicin. The acute maximum tolerance dose (MTD) of legubicin was >16 mg/kg doxorubicin equivalent in female rats, 11 mg/kg doxorubicin equivalent in male rats (LD50 of conventional doxorubicin is 10.51 mg/kg), and >8 mg/kg doxorubicin equivalent in dogs (MTD of conventional doxorubicin is 1.5 mg/kg). Four-week repeat-dose toxicity studies of intravenous legubicin were conducted in rats (5, 10, and 25 mg/kg/dose once weekly) and dogs (3/1.5, 10/5, and 20/10 mg/kg/dose once weekly); the dose levels were reduced from the second dose due to intolerable legubicin-associated toxicity at 20 mg/kg. Major organs of toxicity included the gastrointestinal tract, lymphoid and hematopoietic organs, kidney, skin, liver, reproductive organs, and peripheral nerves, which are all associated with doxorubicin. However, cardiotoxicity was only noted at MTD dose levels. Altogether, our results confirm an improved safety profile of legubicin over conventional doxorubicin and support its clinical benefit for treating cancer.

Transcriptome and proteome analyses reveal that upregulation of GSTM2 by allisartan improves cardiac remodeling and dysfunction in hypertensive rats.

Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker antihypertensive drug, allisartan can control blood pressure, and improve cardiac remodeling and cardiac dysfunction caused by hypertension. The aim of the present study was to investigate the protective effects of allisartan on the heart of spontaneously hypertensive rats (SHRs) and the underlying mechanisms. SHRs were used as an animal model of hypertensive heart disease and were treated with allisartan orally at a dose of 25 mg/kg/day. The blood pressure levels of the rats were continuously monitored, their body and heart weights were measured, and their cardiac structure and function were evaluated using echocardiography. Wheat germ agglutinin staining and Masson trichrome staining were employed to assess the morphology of the myocardial tissue. In addition, transcriptome and proteome analyses were performed using the Solexa/Illumina sequencing platform and tandem mass tag technology, respectively. Immunofluorescence co-localization was conducted to analyze Nrf2 nuclear translocation, and TUNEL was performed to detect the levels of cell apoptosis. The protein expression levels of pro-collagen I, collagen III, phosphorylated (p)-AKT, AKT, p-PI3K and PI3K, and the mRNA expression levels of Col1a1 and Col3a1 were determined by western blotting and reverse transcription-quantitative PCR, respectively. Allisartan lowered blood pressure, attenuated cardiac remodeling and improved cardiac function in SHRs. In addition, allisartan alleviated cardiomyocyte hypertrophy and cardiac fibrosis. Allisartan also significantly affected the 'pentose phosphate pathway', 'fatty acid elongation', 'valine, leucine and isoleucine degradation', 'glutathione metabolism', and 'amino sugar and nucleotide sugar metabolism' pathways in the hearts of SHRs, and upregulated the expression levels of GSTM2. Furthermore, allisartan activated the PI3K-AKT-Nrf2 signaling pathway and inhibited cardiomyocyte apoptosis. In conclusion, the present study demonstrated that allisartan can effectively control blood pressure in SHRs, and improves cardiac remodeling and cardiac dysfunction. Allisartan may also upregulate the expression levels of GSTM2 in the hearts of SHRs and significantly affect glutathione metabolism, as determined by transcriptome and proteome analyses. The cardioprotective effect of allisartan may be mediated through activation of the PI3K-AKT-Nrf2 signaling pathway, upregulation of GSTM2 expression and reduction of cardiomyocyte apoptosis in SHRs.

Discovery of gene regulation mechanisms associated with uniconazole-induced cold tolerance in banana using integrated transcriptome and metabolome analysis.

BACKGROUND: The gibberellic acid (GA) inhibitor, uniconazole, is a plant growth regulator commonly used in banana cultivation to promote dwarfing but also enhances the cold resistance in plants. However, the mechanism of this induced cold resistance remains unclear. RESULTS: We confirmed that uniconazole induced cold tolerance in bananas and that the activities of Superoxide dismutase and Peroxidase were increased in the uniconazole-treated bananas under cold stress when compared with the control groups. The transcriptome and metabolome of bananas treated with or without uniconazole were analyzed at different time points under cold stress. Compared to the control group, differentially expressed genes (DEGs) between adjacent time points in each uniconazole-treated group were enriched in plant-pathogen interactions, MAPK signaling pathway, and plant hormone signal transduction, which were closely related to stimulus-functional responses. Furthermore, the differentially abundant metabolites (DAMs) between adjacent time points were enriched in flavone and flavonol biosynthesis and linoleic acid metabolism pathways in the uniconazole-treated group than those in the control group. Temporal analysis of DEGs and DAMs in uniconazole-treated and control groups during cold stress showed that the different expression patterns in the two groups were enriched in the linoleic acid metabolism pathway. In addition to strengthening the antioxidant system and complex hormonal changes caused by GA inhibition, an enhanced linoleic acid metabolism can protect cell membrane stability, which may also be an important part of the cold resistance mechanism of uniconazole treatment in banana plants. CONCLUSIONS: This study provides information for understanding the mechanisms underlying inducible cold resistance in banana, which will benefit the production of this economically important crop.

Associations of dietary iron intake with cardiovascular disease risk and dyslipidemia among Chinese adults.

BACKGROUND: Whether iron intake can affect cardiovascular disease (CVD) and dyslipidemia is controversial. However, few studies have focused on reducing the risk of CVD in people at risk for dyslipidemia. This study explored the linear relationship and possible nonlinear relationship between CVD and dyslipidemia. METHODS: Dietary data were obtained from the China Health and Nutrition Survey between 2004 and 2015. The survey included 8173 participants older than 18 years. CVD risk was estimated by the Framingham risk score (FRS). Logistic regression analysis was used to determine whether iron intake affects CVD incidence and lipid profiles. The nonlinear association was tested with restricted cubic splines (RCSs). RESULTS: For males, higher total iron intake [the fifth quintile (Q) vs. Q1 odds ratio (OR): 0.335, 95% confidence interval (CI): 0.248-0.453], heme iron intake (OR: 0.679, 95% CI: 0.492-0.937) and non-heme iron intake (OR: 0.362, 95% CI: 0.266-0.492) reduced CVD incidence. Heme iron intake increased high low-density lipoprotein cholesterol (LDL-C) (OR: 1.786, 95% CI: 1.226-2.602), high total cholesterol (TC) (OR: 2.404, 95% CI: 1.575-3.669), high triglyceride (TG) (OR: 1.895, 95% CI: 1.423-2.523), and low apolipoprotein A1/apolipoprotein B (ApoA-1/ApoB) risk (OR: 1.514, 95% CI: 1.178-1.945). Moderate non-heme iron intake reduced high-density lipoprotein cholesterol (HDL-C) incidence (Q5 vs. Q1 OR: 0.704, 95% CI: 0.507-0.979). For females, higher total iron intake (Q5 vs. Q1 OR: 0.362, 95% CI: 0.266-0.492) and non-heme iron intake (OR: 0.347, 95% CI: 0.154-0.781) reduced CVD incidence. Heme iron intake increased high LDL-C (OR: 1.587, 95% CI: 1.160-2.170) and high TC incidence (OR: 1.655, 95% CI: 1.187-2.309). CONCLUSIONS: Men, especially those at risk of developing dyslipidemia, should consume non-heme rather than heme iron to reduce CVD incidence. For women, increased heme iron intake did not reduce CVD incidence. Therefore, women should minimize their heme iron intake to prevent dyslipidemia.

Identification of important modules and biomarkers in diabetic cardiomyopathy based on WGCNA and LASSO analysis.

Background: Diabetic cardiomyopathy (DCM) lacks specific and sensitive biomarkers, and its diagnosis remains a challenge. Therefore, there is an urgent need to develop useful biomarkers to help diagnose and evaluate the prognosis of DCM. This study aims to find specific diagnostic markers for diabetic cardiomyopathy. Methods: Two datasets (GSE106180 and GSE161827) from the GEO database were integrated to identify differentially expressed genes (DEGs) between control and type 2 diabetic cardiomyopathy. We assessed the infiltration of immune cells and used weighted coexpression network analysis (WGCNA) to construct the gene coexpression network. Then we performed a clustering analysis. Finally, a diagnostic model was built by the least absolute shrinkage and selection operator (LASSO). Results: A total of 3066 DEGs in the GSE106180 and GSE161827 datasets. There were differences in immune cell infiltration. According to gene significance (GS) > 0.2 and module membership (MM) > 0.8, 41 yellow Module genes and 1474 turquoise Module genes were selected. Hub genes were mainly related to the "proteasomal protein catabolic process", "mitochondrial matrix" and "protein processing in endoplasmic reticulum" pathways. LASSO was used to construct a diagnostic model composed of OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB and verified it in the GSE163060 and GSE175988 datasets with AUCs of 0.9333 (95% CI: 0.7801-1) and 0.96 (95% CI: 0.8861-1), respectively. H9C2 cells were verified, and the results were similar to the bioinformatics analysis. Conclusion: We constructed a diagnostic model of DCM, and OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB were potential biomarkers, which may provide new insights for improving the ability of early diagnosis and treatment of diabetic cardiomyopathy.

Dissipation behaviours, residues, and health risk of six herbicides in sugar beets under field conditions.

This study established a residue detection method based on the QuEChERS pre-treatment method and combined it with high-performance liquid chromatography-tandem mass spectrometry to test six herbicides (metamitron, clopyralid, desmedipham, phenmedipham, ethofumesate, and haloxyfop-p-methyl) in sugar beet plants, soil, and roots. The degradation dynamics and terminal residues of each herbicide in sugar beets were analysed. Finally, the dietary risks of various herbicides in sugar beets were evaluated based on the dietary structure of Chinese people, and the risk quotient values were below 100%. Using this detection method, all reagents exhibited good linearity (0.9724 ≤ R2 ≤ 0.9998), The limit of quantification (LOQ) ranged from 0.01 to 0.05 mg/L, the matrix effect ranged from -1.2% to -50%, the addition recovery rate ranged from 77.00% to 103.48%, and the relative standard deviation ranged from 1.61% to 16.17%; therefore, all indicators of this method met the residue detection standards. Under field conditions, the half-lives (t1/2) ranged about 0.65 ∼ 2.96 d and 0.38 ∼ 27.59 d in sugar beet plants and soil, respectively. All herbicides were easily degraded in sugar beet plants and soil (t1/2 < 30 d). The terminal residue amounts in the beet plants, soil, and roots ranged from < LOQ to 0.243 mg/kg. The dietary risk assessment of each pesticide was conducted based on the residual median of the terminal residues and the highest residual values on the edible part of the beetroot. The chronic exposure risk quotient (RQc) and acute exposure risk quotient (RQa) values were < 100%, indicating that the residue of each pesticide in beetroot posed low risks to consumers in China at the recommended dosage.

p53-associated miRNAs repress lncRNA ZFAS1 to retard the proliferation of papillary thyroid carcinoma.

INTRODUCTION: Thyroid carcinoma is the most frequent malignancy among endocrine-related tumours. Papillary thyroid carcinoma (PTC) is the main type of thyroid carcinoma, and almost 80% cases of thyroid carcinoma are diagnosed as PTC. The molecular mechanism underlying PTC progression is unclear. This study aims to investigate the potential mechanisms of zinc finger antisense 1 (ZFAS1) function in PTC. MATERIAL AND METHODS: The expression of ZFAS1 and p53 was determined by quantitative polymerase chain analysis (qPCR) in PTC tissues derived from 20 PTC patients. Quantitative chromatin immunoprecipitation assay (qChIP) analysis was performed to validate the target of ZFAS1/p53 and miRNAs/p53. The Gene Expression Omnibus (GEO) dataset GSE94908 was analysed to obtain the differentially expressed p53-associated microRNAs (miRNAs). Luciferase assay validated the target of ZFAS1/miRNAs, and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cell proliferation. RESULTS: The expression of ZFAS1 was up-regulated in the tissues derived from PTC patients, and the expression of ZFAS1 was negatively associated with p53 expression in PTC. The expression of ZFAS1 was significantly higher in the MDA-T120 cells harbouring mutant p53. We validated that ZFAS1 is a direct target of p53. In PTC cells, p53 directly repressed the ZFAS1 expression. In addition, we determined that miR-135b-5p and miR-193a-3p are directly induced by p53 in PTC cells. Interestingly, p53-targeted miR-135b-5p, miR-193a-3p, and miR-34b repressed the expression of ZFAS1 via the seed-matching sequences in the 3'-untranslated region (3'-UTR) of ZFAS1, and thereby suppressed PTC cell proliferation induced by ZFAS1. CONCLUSION: The oncogenic lncRNA ZFAS1 is directly repressed by p53 in PTC. p53-mediated miRNAs including miR-135b 5p, miR-193a-3p, and miR-34b repress ZFAS1 expression, and thereby inhibit the proliferation of PTC.

Using warming tolerances to predict understory plant responses to climate change.

Climate change is pushing species towards and potentially beyond their critical thermal limits. The extent to which species can cope with temperatures exceeding their critical thermal limits is still uncertain. To better assess species' responses to warming, we compute the warming tolerance (ΔTniche ) as a thermal vulnerability index, using species' upper thermal limits (the temperature at the warm limit of their distribution range) minus the local habitat temperature actually experienced at a given location. This metric is useful to predict how much more warming species can tolerate before negative impacts are expected to occur. Here we set up a cross-continental transplant experiment involving five regions distributed along a latitudinal gradient across Europe (43° N-61° N). Transplant sites were located in dense and open forests stands, and at forest edges and in interiors. We estimated the warming tolerance for 12 understory plant species common in European temperate forests. During 3 years, we examined the effects of the warming tolerance of each species across all transplanted locations on local plant performance, in terms of survival, height, ground cover, flowering probabilities and flower number. We found that the warming tolerance (ΔTniche ) of the 12 studied understory species was significantly different across Europe and varied by up to 8°C. In general, ΔTniche were smaller (less positive) towards the forest edge and in open stands. Plant performance (growth and reproduction) increased with increasing ΔTniche across all 12 species. Our study demonstrated that ΔTniche of understory plant species varied with macroclimatic differences among regions across Europe, as well as in response to forest microclimates, albeit to a lesser extent. Our findings support the hypothesis that plant performance across species decreases in terms of growth and reproduction as local temperature conditions reach or exceed the warm limit of the focal species.

A meta-analysis of the changes in the Gut microbiota in patients with intractable epilepsy compared to healthy controls.

OBJECTIVE: To explore gut microbiota changes in intractable epilepsy patients compared to healthy control individuals through meta-analysis. METHODS: PubMed, Web of Science, CNKI, Wanfang, medRxiv, bioRxiv, ilae.org, clinical trial databases, and papers from the International Epilepsy Congress (IEC) were searched, and the literature on the correlation between intractable epilepsy and the gut microbiota reported from database establishment to June 2023 was included. Literature meeting the inclusion criteria was screened, and meta-analysis of the included literature was performed using RevMan5.4 software. RESULTS: Ten case-control studies were included in the meta-analysis. There were 183 patients with intractable epilepsy and 283 healthy control subjects. The analysis results indicated that Bacteroidetes (MD = -0.64, 95 %-CI = -1.21 to -0.06) and Ruminococcaceae (MD = -1.44, 95 % CI = -1.96 to -0.92) were less abundant in the patients with intractable epilepsy than in the normal population. Proteobacteria (MD = 0.53, 95 % CI = 0.02 to 1.05) and Verrucomicrobia (MD = 0.26, 95 % CI = 0.06 to 0.45) were more abundant in the patients with intractable epilepsy than in the normal population. CONCLUSION: This meta-analysis indicated that the abundances of Bacteroidetes and Ruminococcaceae were reduced while those of Proteobacteria and Verrucomicrobia were significantly increased in patients with intractable epilepsy. The above changes in these four taxa of the gut microbiota may have been induced by intractable epilepsy, which may increase the risk of seizures. Their roles in the pathogenesis of intractable epilepsy need to be further explored, and related factors that influence microbiota changes should be considered in future studies.

Endoplasmic reticulum stress-mediated cell death in cardiovascular disease.

The endoplasmic reticulum (ER) plays a vital function in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) can trigger various modes of cell death by activating the unfolded protein response (UPR) signaling pathway. Cell death plays a crucial role in the occurrence and development of diseases such as cancer, liver diseases, neurological diseases, and cardiovascular diseases. Several cardiovascular diseases including hypertension, atherosclerosis, and heart failure are associated with ER stress. ER stress-mediated cell death is of interest in cardiovascular disease. Moreover, an increasing body of evidence supports the potential of modulating ERS for treating cardiovascular disease. This paper provides a comprehensive review of the UPR signaling pathway, the mechanisms that induce cell death, and the modes of cell death in cardiovascular diseases. Additionally, we discuss the mechanisms of ERS and UPR in common cardiovascular diseases, along with potential therapeutic strategies.

Transcriptomic and metabolomic differences between banana varieties which are resistant or susceptible to Fusarium wilt.

Background: Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense race 4 (Foc4), is the most lethal disease of bananas in Asia. Methods: To better understand the defense response of banana to Fusarium wilt, the transcriptome and metabolome profiles of the roots from resistant and susceptible bananas inoculated with Foc4 were compared. Results: After Foc4 inoculation, there were 172 and 1,856 differentially expressed genes (DEGs) in the Foc4-susceptible variety (G1) and Foc4-resistant variety (G9), respectively. In addition, a total of 800 DEGs were identified between G1 and G9, which were mainly involved in the oxidation-reduction process, cell wall organization, phenylpropanoid biosynthesis, and lipid and nitrogen metabolism, especially the DEGs of Macma4_08_g22610, Macma4_11_g19760, and Macma4_03_g06480, encoding non-classical arabinogalactan protein; GDSL-like lipase; and peroxidase. In our study, G9 showed a stronger and earlier response to Foc4 than G1. As the results of metabolomics, lipids, phenylpropanoids and polyketides, organic acids, and derivatives played an important function in response to Fusarium wilt. More importantly, Macma4_11_g19760 might be one of the key genes that gave G9 more resistance to Foc4 by a lowered expression and negative regulation of lipid metabolism. This study illustrated the difference between the transcriptomic and metabolomic profiles of resistant and susceptible bananas. These results improved the current understanding of host-pathogen interactions and will contribute to the breeding of resistant banana plants.

Risk of allergic rhinitis in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Numerous parallels exist between inflammatory bowel disease (IBD) and allergic rhinitis (AR), which include risk factors (such as environmental and genetic factors), pathogenesis (immune disorders, epithelial cell barriers, etc.), and treatment (immunosuppressants and immunomodulators, such as cyclosporine and steroids). However, the risk of AR in IBD patients is unknown. OBJECTIVE: In this systematic review and meta-analysis, patients with IBD are examined for their risk of AR. METHODS: Several databases are accessible in both Chinese and English, including PubMed, BioRXiv, WanFang, the China National Knowledge Infrastructure (CNKI), Web of Science, METSTR, and MedRxiv. Findings presented at allergy, rhinology, thoracic, and gastrointestinal conferences were analyzed. Based on the inclusion and exclusion criteria, two evaluators independently retrieved data, read the literature, and evaluated bias risk. The data analysis was conducted using RevMan 5.4. Case-control and cohort studies were eligible study designs for this research. RESULTS: There were 10 case-control studies and 1 cohort study included in the meta-analysis. The experimental group consisted of 65,687 IBD patients, of whom 5838 had AR. A total of 345,176 participants without IBD were included in the control group, of whom 24,625 developed AR. The outcomes demonstrated that IBD patients had a higher risk of developing AR (odds ratio [OR] = 1.48, 95% confidence interval [CI] [1.12, 1.95], Z = 2.78, P = 0.005) than those without IBD. CONCLUSION: The risk of AR is higher in IBD patients. Further investigation is required to determine the mechanism behind the association between AR and IBD.

Responses of plant carbon and nitrogen assimilations to nitrogen addition in a subtropical forest: Canopy addition vs. understory addition.

The global atmospheric nitrogen (N) deposition has intensified in recent years, resulting in a complex impact on forest ecosystems. This study investigated the effects of canopy (CAN) and understory additions of N (UAN) on leaf carbon (C) and N assimilations, as well as growth parameters of representative woody plant species in an evergreen broad-leaved forest, i.e. Castanea henryi, Schefflera heptaphylla, Blastus cochinchinensis, and Lasianthus chinensis. The results showed that leaf N assimilation key enzyme nitrate reductase (NR) activities of B. cochinchinensis and S. heptaphylla were significantly decreased by UAN, and were significantly decreased by CAN for C. henryi. CAN significantly decreased the nitrite reductase activity of C. henryi, while significantly increased that of L. chinensis. However, the Amax values of each woody species were not significantly different among control (CK), CAN, and UAN. Community surveys demonstrated that CAN and UAN inhibited the growth (diameter at breast height, height, or crown width) of the representative large tree, C. henryi, while promoting the growths of understory woody species (B. cochinchinensis and L. chinensis). Overall, N addition was found to change the physiological processes of N and C metabolisms of the dominant woody species in an evergreen broad-leaved forest. The community of subtropical evergreen broad-leaved forests may further decline and its C fixation capacity may be detrimentally changed under N deposition in the future.

Untangling the impact of plantation type and functional traits on ecosystem nutrient stocks in an experimentally restored forest ecosystem.

The primary objective of ecological restoration is recovering biodiversity and ecosystem functioning. While a functional trait-based approach can help understand community assembly and ecosystem function recovery during ecological restoration, there still exists a knowledge gap in assessing how functional traits indicate the mediating roles of the plant community in response to forest restoration effects on ecosystem functions. This study applied the "response-effect trait" framework to investigate experimentally whether the treatment of plantation type has an impact on community trait compositions, which in turn could affect forest ecosystem nutrient stocks - here, carbon (C) and nitrogen (N) and phosphorus (P) stocks in tree, understory, litter and soil pools at an experimental station in subtropical China. We used structural equation models (SEMs) to examine the relationships among plantation type, community weighted mean of traits, and nutrient stocks in each pool. Our results show that most of the tree and understory traits studied were response traits to plantation type. Moreover, certain traits played a significant role in mediating plantation-type effects on C, N and P stocks for understory pool (e.g., understory stem specific density and specific leaf area, tree leaf phosphorus content), and for litter and soil pools (e.g., tree leaf carbon or phosphorus content, understory specific leaf area, leaf nitrogen or phosphorus content), known as "response-effect traits". For the tree pool, only effect traits, and no "response-effect" tree traits, were found for the N stock. Total effects of SEMs indicated that, understory or tree traits can have a greater impact than plantation type on understory or litter C, N or P stocks. After approximately 35 years of natural restoration, exotic plantations exhibited a different community trait characteristic from native plantations. The important roles of traits in mediating the effects of plantation type on non-tree pool C, N and P stocks were highlighted.

The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia.

BACKGROUND: Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. METHODS: This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. RESULTS: In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P < 0.05). Furthermore, when compared to the fasting blood glucose (FBG) or triglyceride (TG) level, the TyG index had a greater area under the ROC curve for predicting coronary lesions and carotid plaques. The subgroup analysis demonstrated the TyG index to be an equally effective predictor of coronary and carotid artery disease, regardless of diabetes and hyperlipidaemia. CONCLUSION: The TyG index is a useful marker for predicting coronary and carotid atherosclerosis in patients with symptomatic CAD, regardless of diabetes mellitus and hyperlipidaemia. The TyG index is of higher value for the identification of both coronary and carotid atherosclerotic plaques than the FBG or TG level alone.