Long-term blood pressure variability and risk of cardiovascular diseases in populations with different blood pressure status: an ambispective cohort study.

OBJECTIVE: We aimed to investigate the correlation between long-term blood pressure variability (BPV) and the risk of cardiovascular diseases (CVDs) among population with different blood pressure statuses (normotension, well-controlled hypertension, and uncontrolled hypertension). METHODS: In this ambispective cohort study, CVD-free residents aged over 50 years were consecutively enrolled from two community health service centers (CHCs) in Tianjin, China from April 2017 to May 2017. Information on blood pressure was retrospectively extracted from electronic medical records of CHCs between January 2010 and May 2017, and the occurrence of new-onset CVDs was prospectively observed during follow-up until September 2019. Long-term variation of SBP and DBP was assessed using four indicators: SD, coefficient of variation (CV), average successive variability (ASV), and average real variability (ARV). Cox proportional hazards regression model was developed to identify the potential impact of BPV on the incidence of CVDs. The receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of BPV indicators for the occurrence of CVDs. RESULTS: Of 1275 participants included, 412 (32.3%) experienced new CVD events during the median 7.7 years of follow-up, with an incidence density of 499/10 000 person-year in the whole cohort. Cox regression analysis revealed that almost all SBP and DBP variability indicators (except for SBP-SD) were significantly related to the risk of CVDs, especially among individuals with well-controlled hypertension. A trend toward an increased risk of CVDs across BPV quartiles was also observed. Moderate predictive abilities of BPV were observed, with the area under ROC curves ranging between 0.649 and 0.736. For SBP variability, SD had the lowest predictive ability, whereas for DBP variability, ARV had the lowest predictive ability. No significant association of CVDs with SBP-SD was found in all analyses, no matter as a continuous or categorical variable. CONCLUSION: Elevated long-term BPV is associated with an increased risk of CVDs, especially among individuals with well-controlled hypertension. CV and ASV had higher predictive values than SD and ARV.

Cultivation of novel Atribacterota from oil well provides new insight into their diversity, ecology, and evolution in anoxic, carbon-rich environments.

BACKGROUND: The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. RESULTS: We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. CONCLUSION: Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract.

[Spatiotemporal variation and driving factors of vegetation coverage in Shanxi Province, China]. / å±±è¥¿çœæ¤è¢«è¦†ç›–åº¦çš„æ—¶ç©ºå˜åŒ–åŠé©±åŠ¨å› å­.

Understanding the spatiotemporal variations and driving factors of regional vegetation coverage is crucial for developing scientific plans for ecological environment protection and maintaining regional ecological balance. Based on the Google Earth Engine (GEE) platform and using Landsat Collection 2 data, we investigated the spatiotemporal variation and driving factors of vegetation coverage in Shanxi Province, China, from 1990 to 2020, by employing methods such as pixel-based binary model, trend analysis, zonal statistics, and geodetector. The results showed that vegetation coverage in Shanxi Province showed a fluctuating upward trend from 1990 to 2020. Vegetation coverage in 44.4% of this region had been significantly improved, and the area with significant degradation accounted for 7.4%. Vegetation coverage in Shanxi Province was positively correlated with elevation, slope, and mountain terrain relief. The area proportion of vegetation coverage growth was the highest in the plateau and hilly regions. Factor detection results showed that land use type, landform type, annual average precipitation, and soil type were the main influencing factors of the spatial differentiation of vegetation coverage in Shanxi Province. Results of the interaction detection showed that the interaction between driving factors all showed enhancement. The interaction between natural factors showed a downward trend, while the interaction results of social factors showed an upward trend, reflecting that the impacts of human activities on vegetation coverage in Shanxi Province were gradually increasing.

Regulation of FSP1 myristoylation by NADPH: A novel mechanism for ferroptosis inhibition.

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis in the pathogenesis of excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show that exogenous NADPH, besides being reductant, interacts with N-myristoyltransferase 2 (NMT2) and upregulates the N-myristoylated ferroptosis suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 and strengthens resistance to ferroptosis. Arg-291 of NMT2 is critical for the NADPH-NMT2-FSP1 axis-mediated suppression of ferroptosis. This study suggests that NMT2 plays a pivotal role by bridging NADPH levels and neuronal susceptibility to ferroptosis. We propose a mechanism by which the NADPH regulates N-myristoylation, which has important implications for ferroptosis and disease treatment.

Zn-Mediated Fragmentation of N-Alkoxyphthalimides Enabling the Synthesis of gem-Difluoroalkenes.

Zn-mediated generation of alkoxyl radicals from N-alkoxyphthalimides emerged as an efficient approach for forming diverse and valuable alkyl radicals through ß-scission or a hydrogen atom transfer process. The alkyl radical species can be further trapped by α-trifluoromethyl alkenes to construct a series of gem-difluoroalkenes.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

Effects of simulated microgravity on current generation of electrochemically active bacteria: Insights from case-control study using random positioning machine.

Electrochemically active bacteria (EAB) exhibit promising prospects for space exploration and life support systems. However, the effects of the space environment on EAB are unclear. In this study, the effects of simulated microgravity on the current generation of mixed-culture EAB were illustrated, and the underlying mechanism was elucidated. The results demonstrated that the electrochemical activity of mixed-culture EAB was enhanced, which was mainly due to the enrichment of Geobacter and the increase in EAB biomass. Additionally, the genes and proteins of the biofilm changed obviously under simulated microgravity conditions, including: I) genes related to signal transfer, II) genes related to cell wall synthesis, and III) genes related to riboflavin synthesis. This study first revealed the enrichment in EAB abundance, the increase in EAB biomass, and the promotion of current generation under simulated microgravity.

The efficacy of Omega-3 polyunsaturated fatty acids for severe burn patients: A systematic review and trial sequential meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Severe burns lead to metabolic changes, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Omege-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties. In the absence of substantial evidence for use on major burns, we systematically reviewed the efficacy of omega-3 PUFAs for patients with severe burns. METHODS: We comprehensively searched MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, Wang Fang Data, Chinese Biomedicine Database, and Science Direct databases to collect randomised controlled trials of omega-3 PUFAs administered to patients with burns from January 2000 to June 2023. Two researchers independently screened the literatures, extracted the data, and assessed the risk of bias in the included studies. The outcomes were mortality, the risk of severe sepsis, septic shock, and multiple organ dysfunction syndrome. Data synthesis was conducted using Review Manager. Trial sequential analyses (TSA) for outcomes were performed. RESULTS: Three randomised controlled trials involving 140 patients were included. Of these, 71 patients received omega-3 PUFAs. The results showed that omega-3 PUFAs significantly reduced the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome (RR = 0.38, 95 % CI [0.19, 0.75], P = 0.005), C-reactive protein levels (MD = -39.70[-81.63, 2.23], P = 0.06), and improved respiratory outcomes. However, there was no difference in 14-day mortality (RR = 1.10, 95%CI [0.59, 2.05], P = 0.75). TSA showed that the results for the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome are insufficient and inconclusive. CONCLUSIONS: Omega-3 PUFAs may reduce inflammatory response and risk of sepsis, septic shock, and multiple organ dysfunction syndrome in severe burns patients and may shorten hospital stay but cannot reduce risk of death. Due to the limitation of the quantity and quality of the included studies, the evidence level is low, and the conclusions need to be verified by larger scale and higher quality randomised controlled trials.

Artificial intelligence-assisted diagnosis of congenital heart disease and associated pulmonary arterial hypertension from chest radiographs: A multi-reader multi-case study.

OBJECTIVES: To explore the possibility of automatic diagnosis of congenital heart disease (CHD) and pulmonary arterial hypertension associated with CHD (PAH-CHD) from chest radiographs using artificial intelligence (AI) technology and to evaluate whether AI assistance could improve clinical diagnostic accuracy. MATERIALS AND METHODS: A total of 3255 frontal preoperative chest radiographs (1174 CHD of any type and 2081 non-CHD) were retrospectively obtained. In this study, we adopted ResNet18 pretrained with the ImageNet database to establish diagnostic models. Radiologists diagnosed CHD/PAH-CHD from 330/165 chest radiographs twice: the first time, 50% of the images were accompanied by AI-based classification; after a month, the remaining 50% were accompanied by AI-based classification. Diagnostic results were compared between the radiologists and AI models, and between radiologists with and without AI assistance. RESULTS: The AI model achieved an average area under the receiver operating characteristic curve (AUC) of 0.948 (sensitivity: 0.970, specificity: 0.982) for CHD diagnoses and an AUC of 0.778 (sensitivity: 0.632, specificity: 0.925) for identifying PAH-CHD. In the 330 balanced (165 CHD and 165 non-CHD) testing set, AI achieved higher AUCs than all 5 radiologists in the identification of CHD (0.670-0.858) and PAH-CHD (0.610-0.688). With AI assistance, the mean ± standard error AUC of radiologists was significantly improved for CHD (ΔAUC + 0.096, 95 % CI: 0.001-0.190; P = 0.048) and PAH-CHD (ΔAUC + 0.066, 95 % CI: 0.010-0.122; P = 0.031) diagnosis. CONCLUSION: Chest radiograph-based AI models can detect CHD and PAH-CHD automatically. AI assistance improved radiologists' diagnostic accuracy, which may facilitate a timely initial diagnosis of CHD and PAH-CHD.

Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.

BACKGROUND: We aimed to assess differences in intestinal microflora between patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) and those without MVI. Additionally, we investigated the potential of the microbiome as a non-invasive biomarker for patients with MVI. METHODS: We analyzed the preoperative gut microbiomes (GMs) of two groups, the MVI (n = 46) and non-MVI (n = 56) groups, using 16S ribosomal RNA gene sequencing data. At the operational taxonomic unit level, we employed random forest models to predict MVI risk and validated the results in independent validation cohorts [MVI group (n = 17) and non-MVI group (n = 15)]. RESULTS: ß diversity analysis, utilizing weighted UniFrac distances, revealed a significant difference between the MVI and non-MVI groups, as indicated by non-metric multidimensional scaling and principal coordinate analysis. We also observed a significant correlation between the characteristic intestinal microbial communities at the genus level and their main functions. Nine optimal microbial markers were identified, with an area under the curve of 79.76% between 46 MVI and 56 non-MVI samples and 79.80% in the independent verification group. CONCLUSION: This pioneering analysis of the GM in patients with operable HBV-HCC with and without MVI opens new avenues for treating HBV-HCC with MVI. We successfully established a diagnostic model and independently verified microbial markers for patients with MVI. As preoperative targeted biomarkers, GM holds potential as a non-invasive tool for patients with HBV-HCC with MVI.

Multicopy Chromosome Integration and Deletion of Negative Global Regulators Significantly Increased the Heterologous Production of Aborycin in Streptomyces coelicolor.

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems.

[Characteristics of gut microbiome communities in the invasive African giant snail under urbanization gradient]. / åŸŽå¸‚åŒ–æ¢¯åº¦ä¸‹å ¥ä¾µç”Ÿç‰©éžæ´²å¤§èœ—ç‰›è‚ é“å¾®ç”Ÿç‰©ç¾¤è½ç‰¹å¾.

To investigate the diversity and community structure of gut microbiome of the invasive species, Achatina fulica, along an urbanization gradient, we collected 30 A. fulica samples from five parks in the urban, suburban, and rural areas of Xiamen City. Using full-length 16S rRNA gene sequencing performed by the third generation PacBio sequencing platform, we analyzed the community characteristics of gut microbiome and soil microbiome in different habitats. We found a significant disparity between the composition of gut microbiome of A. fulica and that of the soil microbiome in their habitats. Furthermore, the gut microbiome of A. fulica were more sensitive to urbanization. The microbial α-diversity indices (Sobs, Chao, Shannon indices) in the soil of A. fulica habitats were consistently higher than those within their guts. Despite the similar ß-diversity indices of microbial communities in urban, suburban, and rural soils, we found a significant discrepancy in gut microbiome composition. Urbanization significantly influenced A. fulica gut microbiome composition. Gut microbiome of A. fulica in urban and suburban regions primarily consisted of Enterobacteriaceae, Xanthomonadaceae, and Mycoplasmataceae, while that in rural areas chiefly composed of Streptococcaceae and Paenibacillaceae. The diversity and abundance of potential human pathogenic bacteria within the gut microbiome of A. fulica significantly increased in urban environments, suggesting that urbanization escalated the risk of A. fulica transmitting potential pathogens.

Instant water toxicity detection based on magnetically-constructed electrochemically active biofilm.

Water toxicity determination with electrochemically active bacteria (EAB) is promising in the early warning of water pollution. However, limited by tedious biofilm formation, natural EAB biofilms are uncapable of the instant detection of water toxicity, resulting in the failure for the emergency monitoring of water pollution. To solve this problem, a novel method for the rapid construction of EAB biofilms using magnetic adsorption was established, and the performance of instant water toxicity detection with magnetically-constructed EAB biofilm was investigated. The results demonstrate that EAB biofilms were magnetically constructed in less than 30 min, and magnetically-constructed EAB biofilm generated stable currents even under continuous flow conditions. Magnetically-constructed EAB biofilms realized instant water toxicity detection, and the sensitivity increased with the decrease of magnetic field intensity. Low magnetic field intensity resulted in a loose biofilm structure, which is conducive to toxic pollutant penetration. The detection limit for Cu2+, phenol, and Cd2+ achieved 0.07 mg/L with optimal magnetic field intensity, and the detection time was less than 30 min. This study broadens the application of water toxicity determination with EAB, and establishes a foundation for the instant and continuous detection of water toxicity with EAB.

Mechanism and applications of bidirectional extracellular electron transfer of Shewanella.

Electrochemically active microorganisms (EAMs) play an important role in the fields of environment and energy. Shewanella is the most common EAM. Research into Shewanella contributes to a deeper comprehension of EAMs and expands practical applications. In this review, the outward and inward extracellular electron transfer (EET) mechanisms of Shewanella are summarized and the roles of riboflavin in outward and inward EET are compared. Then, four methods for the enhancement of EET performance are discussed, focusing on riboflavin, intracellular reducing force, biofilm formation and substrate spectrum, respectively. Finally, the applications of Shewanella in the environment are classified, and the restrictions are discussed. Potential solutions and promising prospects for Shewanella are also provided.

Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has been confirmed to contribute to brain injury in ischemic stroke via promoting excitotoxicity and necroptosis. Telaprevir, a hepatitis C virus protease inhibitor, is predicted to be a potential MALT1 inhibitor. Here, we showed that telaprevir protected against cerebral ischemic injury via inhibiting MALT1, thereby preventing glutamate receptor ionotropic NMDA 2B (GluN2B) activation, limiting calcium overload, and suppressing necroptosis. In ischemic stroke mice, telaprevir reduced infarct volume, improved the long-term survival rate, and enhanced sensorimotor, memory, and cognitive functions. In hypoxia-treated nerve cells, telaprevir decreased the intracellular calcium concentrations and reduced LDH release. Mechanistically, telaprevir inhibited MALT1 protease activity, thus decreasing the membrane protein level of GluN2B and its phosphorylation through reducing the level of STEP61. Moreover, telaprevir was able to inhibit the levels of necroptosis-associated proteins. According to these results, it can be concluded that telaprevir alleviates neuronal brain injury in stroke mice via restraining GluN2B activation and suppresses the receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway through inhibiting MALT1. Thus, telaprevir might have a novel indication for treating patients with ischemic stroke.

Nomograms for postsurgical extrahepatic recurrence prediction of hepatocellular carcinoma based on presurgical circulating tumor cell status and clinicopathological factors.

BACKGROUND AND AIMS: Extrahepatic recurrence (EHR) is one of the major reasons for the poor prognosis of hepatocellular carcinoma (HCC). The present study aimed to develop and assess the performance of predictive models by using a combination of presurgical circulating tumor cell (CTCs) data and clinicopathological features to screen patients at high risk of EHR to achieve precise decision-making. PATIENTS AND METHODS: A total of 227 patients with recurrent HCC and preoperative CTC data from January 2014 to August 2019 were enrolled. All patients were randomly assigned to one of two cohorts: development or validation. Two preoperative and postoperative nomogram models for EHR prediction were developed and multi-dimensionally validated. RESULTS: Patients with EHR had generally lower recurrence-free survival (p < 0.001), and overall survival (p < 0.001), and significantly higher CTC counts (epithelial CTCs, epithelial/mesenchymal hybrid CTCs, and mesenchymal CTCs count, all p < 0.05) than those without EHR. Univariate and multivariate analyses revealed that EHR was associated with four risk factors in the development cohort: total CTC count (p = 0.014), tumor size (p = 0.028), node number (p = 0.045), and microvascular invasion (p = 0.035). These factors were incorporated into two nomogram models (preoperative and postoperative), which reliably predicted EHR through multidimensional verification (e.g., calibration plot, receiver operating characteristic analysis, decision curve analysis, and clinical impact curve analysis) in the development and validation cohorts, respectively. With threshold of scores of 100.3 and 176.8 before and after surgery respectively, both nomograms were able to stratify patients into two distinct prognostic subgroups (all p < 0.05). CONCLUSION: The present study proposed two nomogram models integrating presurgical CTC counts and clinicopathological risks and showed relatively good predictive performance of EHR, which may be beneficial to the clinical practice of HCC recurrence. Further multicenter studies are needed to assess its general applicability.

Bacillus licheniformis prevents and reduces anxiety-like and depression-like behaviours.

As common mental disorders, depression and anxiety impact people all around the world. Recent studies have found that the gut microbiome plays an important role in mental health. It is becoming possible to treat mental disorders by regulating the composition of the gut microbiota. Bacillus licheniformis is a probiotic used to treat gut diseases through balancing the gut microbiome during lasting years. Considering the role of gut microbiota in the gut-brain axis, this study used chronic unpredictable mild stress (CUMS) model rats to explore whether Bacillus licheniformis can prevent and treat depression and anxiety. We found that B. licheniformis reduced the depressive-like and anxiety-like behaviours of the rats during the CUMS process. Meanwhile, B. licheniformis changed the gut microbiota composition; increased the short chain fatty acids (SCFAs) in the colon, decreased kynurenine, norepinephrine, and glutamate levels; and increased the tryptophan, dopamine, epinephrine, and γ-aminobutyric acid (GABA) in the brain. After correlation analysis, we found Parabacteroides, Anaerostipes, Ruminococcus-2, and Blautia showed significant correlation with neurotransmitters and SCFAs, indicating the gut microbiome plays an important role in B. licheniformis reducing depressive-like behaviours. Therefore, this study suggested B. licheniformis may prevent depressive-like and anxiety-like behaviours while regulating the gut microbiota composition and increasing the SCFA levels in the colon to alter the levels of the neurotransmitters in the brain. KEY POINTS: • B. licheniformis reduced depressive-like and anxiety-like behaviours induced by the chronic unpredictable mild stress. • GABA levels in the brain are assonated with B. licheniformis regulating depressive-like and anxiety-like behaviours. • Gut microbiota composition alteration followed by metabolic changes may play a role in the GABA levels increase.

Inhibition of MALT1 reduces ferroptosis in rat hearts following ischemia/reperfusion via enhancing the Nrf2/SLC7A11 pathway.

The dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and/or solute carrier family 7 member 11 (SLC7A11) is believed to contribute to ferroptosis in the hearts suffered ischemia/reperfusion (I/R), but the mechanisms behind the dysregulation of them are not fully elucidated. Mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) can function as a paracaspase to cleave specified substrates and it is predicted to interact with Nrf2. This study aims to explore whether targeting MALT1 can reduce I/R-induced ferroptosis via enhancing the Nrf2/SLC7A11 pathway. The SD rat hearts were subjected to 1h-ischemia plus 3h-reperfusion to establish the I/R injury model, which showed myocardial injuries (increase in infarct size and creatine kinase release) and up-regulation of MALT1 while downregulation of Nrf2 and SLC7A11 concomitant with the increased ferroptosis, reflecting by an increase in glutathione peroxidase 4 (GPX4) level while decreases in the levels of acyl-CoA synthetase long chain family member 4 (ACSL4), total iron, Fe2+ and lipid peroxidation (LPO); these phenomena were reversed in the presence of MI-2, a specific inhibitor of MALT1. Consistently, similar results were achieved in the cultured cardiomyocytes subjected to 8h-hypoxia plus 12h-reoxygenation. Furthermore, micafungin, an antifungal drug, could also exert beneficial effect on mitigating myocardial I/R injury via inhibition of MALT1. Based on these observations, we conclud that inhibition of MALT1 can reduce I/R-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction.

Restoration of metal homeostasis: a potential strategy against neurodegenerative diseases.

Metal homeostasis is critical to normal neurophysiological activity. Metal ions are involved in the development, metabolism, redox and neurotransmitter transmission of the central nervous system (CNS). Thus, disturbance of homeostasis (such as metal deficiency or excess) can result in serious consequences, including neurooxidative stress, excitotoxicity, neuroinflammation, and nerve cell death. The uptake, transport and metabolism of metal ions are highly regulated by ion channels. There is growing evidence that metal ion disorders and/or the dysfunction of ion channels contribute to the progression of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Therefore, metal homeostasis-related signaling pathways are emerging as promising therapeutic targets for diverse neurological diseases. This review summarizes recent advances in the studies regarding the physiological and pathophysiological functions of metal ions and their channels, as well as their role in neurodegenerative diseases. In addition, currently available metal ion modulators and in vivo quantitative metal ion imaging methods are also discussed. Current work provides certain recommendations based on literatures and in-depth reflections to improve neurodegenerative diseases. Future studies should turn to crosstalk and interactions between different metal ions and their channels. Concomitant pharmacological interventions for two or more metal signaling pathways may offer clinical advantages in treating the neurodegenerative diseases.