Outcomes of patients aged ≥26 years with relapsed or refractory B-cell acute lymphoblastic leukemia in ZUMA-3 and historical trials.

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the USA and European Union (EU) for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL; aged ≥26 years in EU). Here, outcomes for patients with R/R B-ALL aged ≥26 years in ZUMA-3 treated with brexu-cel were compared with historical standard-of-care (SOC) therapy. After median follow-up of 26.8 months, the overall complete remission (CR) rate among patients treated with brexu-cel in Phase 2 (N = 43) was 72% and median overall survival (OS) was 25.4 months (95% CI, 15.9-NE). Median OS was improved in Phase 2 patients versus matched historical SOC-treated patients. Compared with aggregate historical trial data, Phase 1 and 2 patients had improved OS versus blinatumomab, inotuzumab, and chemotherapy in a matching-adjusted indirect comparison (MAIC) study. These data demonstrate clinical benefit of brexu-cel relative to SOC in patients ≥26 years with R/R B-ALL.

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Molecular and immunological characteristics of postoperative relapse in lymph node-positive esophageal squamous cell cancer.

BACKGROUND: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. METHODS: A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. RESULTS: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). CONCLUSION: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.

TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing cholesterol efflux capacity in macrophage.

Cholesterol efflux capacity (CEC) dysfunction in macrophages is important in atherosclerosis. However, the mechanism underlying CEC dysfunction remains unclear. We described the characteristics of ATF4 and inflammasome activation in macrophages during atherosclerosis through scRNA sequencing analysis. Then model of hyperlipemia was established in ApoE-/- mice; some were treated with tauroursodeoxycholic acid (TUDCA). TUDCA decreased the ATF4, Hspa, and inflammasome activation, reduced plaque area of the artery, and promoted CEC in macrophages. Furthermore, TUDCA abolished oxLDL-induced foam cell formation by inhibiting activation of the PERK/eIF2α/ATF4 and AIM2 inflammasome in macrophages. Further assays revealed ATF4 binding to AIM2 promoter, promoting its transcriptional activity significantly. Then we discovered that ATF4 affected AIM2-mediated foam cell formation by targeting ABCA1, which could be blocked by TUDCA. Our study demonstrated that TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing CEC of macrophage, which provided possibilities for the development of therapies.

Bringing Artificial Intelligence (AI) into Environmental Toxicology Studies: A Perspective of AI-Enabled Zebrafish High-Throughput Screening.

The booming development of artificial intelligence (AI) has brought excitement to many research fields that could benefit from its big data analysis capability for causative relationship establishment and knowledge generation. In toxicology studies using zebrafish, the microscopic images and videos that illustrate the developmental stages, phenotypic morphologies, and animal behaviors possess great potential to facilitate rapid hazard assessment and dissection of the toxicity mechanism of environmental pollutants. However, the traditional manual observation approach is both labor-intensive and time-consuming. In this Perspective, we aim to summarize the current AI-enabled image and video analysis tools to realize the full potential of AI. For image analysis, AI-based tools allow fast and objective determination of morphological features and extraction of quantitative information from images of various sorts. The advantages of providing accurate and reproducible results while avoiding human intervention play a critical role in speeding up the screening process. For video analysis, AI-based tools enable the tracking of dynamic changes in both microscopic cellular events and macroscopic animal behaviors. The subtle changes revealed by video analysis could serve as sensitive indicators of adverse outcomes. With AI-based toxicity analysis in its infancy, exciting developments and applications are expected to appear in the years to come.

Remediation of Metal Oxide Nanotoxicity with a Functional Amyloid.

Understanding the environmental health and safety of nanomaterials (NanoEHS) is essential for the sustained development of nanotechnology. Although extensive research over the past two decades has elucidated the phenomena, mechanisms, and implications of nanomaterials in cellular and organismal models, the active remediation of the adverse biological and environmental effects of nanomaterials remains largely unexplored. Inspired by recent developments in functional amyloids for biomedical and environmental engineering, this work shows their new utility as metallothionein mimics in the strategically important area of NanoEHS. Specifically, metal ions released from CuO and ZnO nanoparticles are sequestered through cysteine coordination and electrostatic interactions with beta-lactoglobulin (bLg) amyloid, as revealed by inductively coupled plasma mass spectrometry and molecular dynamics simulations. The toxicity of the metal oxide nanoparticles is subsequently mitigated by functional amyloids, as validated by cell viability and apoptosis assays in vitro and murine survival and biomarker assays in vivo. As bLg amyloid fibrils can be readily produced from whey in large quantities at a low cost, the study offers a crucial strategy for remediating the biological and environmental footprints of transition metal oxide nanomaterials.

Effect of "needle sensation" and the real-time changes in autonomic nervous system activity during acupuncture analgesia.

Introduction: Acupuncture analgesia (AA) is widely used in clinical practice. The autonomic nervous system (ANS) may be an important pathway for acupuncture signal transduction. However, real-time changes in autonomic function during AA and the effect of "needle sensation" remain unclear. Methods: We established a human pain model in healthy adults and randomly assigned 128 participants to the model, sham acupuncture, and acupuncture groups in a 1:1:2 ratio. Heart rate variability (HRV), including total power (TP), low-frequency power (LF), high-frequency power (HF), ratio of LF to HF (LF/HF), standard deviation of the normal-normal intervals (SDNN), and root mean square of successive interval differences (RMSSD), were used to assess autonomic function. The visual analog scale (VAS) and efficiency were used to assess the analgesic effect of acupuncture. The Massachusetts General Hospital acupuncture sensation scale (MASS) was used to indicate the intensity of the needle sensation. Anxiety levels were also measured. Finally, the correlation of MASS with HRV, VAS, and anxiety levels was analyzed. Results: VAS decreased after 10 min of needling and 5 min after needle withdrawal in the acupuncture group compared with those in the model group (p = 0.038, p = 0.020). The efficacy rates were 82.0, 50.0, and 61.3% in the acupuncture, model, and sham groups, respectively. These represent significant differences between the acupuncture group and the model and sham acupuncture groups (p < 0.001 in each case). No differences were observed between the model and sham acupuncture groups. HF, TP, SDNN, and RMSSD were all increased in the acupuncture group compared with those in the model group (p = 0.045, p = 0.041, p = 0.002, p = 0.006, respectively). No differences were observed in the sham acupuncture group compared to the model group (p = 0.632, p = 0.542, p = 0.093, p = 0.222, respectively). The LF and LF/HF did not differ among all three groups. A positive correlation was observed between MASS and RMSSD2, LF2, RMSSD4, TP4, VAS5, and anxiety levels. Conclusion: AA was associated with enhanced vagal activity. The intensity of needle sensation was positively correlated with vagal and sympathetic nerve activities. Acupuncture is an effective means of regulating autonomic function, and needle sensation may be an important modulator.

Residue K28 of Zika Virus NS5 Protein Is Implicated in Virus Replication and Antagonism of STAT2.

The identification of four potential nonstructural 5 (NS5) residues-K28, K45, V335, and S749-that share the same amino acid preference in STAT2-interacting flaviviruses [Dengue virus (DENV) and Zika virus (ZIKV)], but not in STAT2-non-interacting flaviviruses [West Nile virus (WNV) and/or Yellow fever virus (YFV)] from an alignment of multiple flavivirus NS5 sequences, implied a possible association with the efficiency of ZIKV to antagonize the human signal transducer and activator of transcription factor 2 (STAT2). Through site-directed mutagenesis and reverse genetics, mutational impacts of these residues on ZIKV growth in vitro and STAT2 antagonism were assessed using virus growth kinetics assays and STAT2 immunoblotting. The results showed that mutations at the residue K28 significantly reduced the efficiency of ZIKV to antagonize STAT2. Further investigation involving residue K28 demonstrated its additional effects on the phenotypes of ZIKV-NS5 nuclear bodies. These findings demonstrate that K28, identified from sequence alignment, is an important determinant of replication and STAT2 antagonism by ZIKV.

Co-exposure of polystyrene nanoplastics and copper induces development toxicity and intestinal mitochondrial dysfunction in vivo and in vitro.

Nanoplastics (NPs) have raised concerns about the combined toxicity to living organisms due to their ability to adsorb heavy metals. There is still uncertainty, however, whether NPs combined with heavy metals exert adverse effects on intestinal microenvironment, especially the intestinal cells and microbiota. Herein, the combined effects of 500 nm spherical-shaped polystyrene nanoplastics (PSNPs) and copper ions (Cu2+) on intestinal cells and gut microbiota were assessed using HCT-116 cells and zebrafish models. The combined exposure of PSNPs (10 mg/L) and Cu2+ (0.5 mg/L) induced more severer hatching interference of zebrafish embryos, deformation, and mortality. In larval stage, PSNPs (10 mg/L) accumulated and carried more Cu2+ in the gastrointestinal tract (GIT) of zebrafish after co-exposure for 5 days. Excessive neutrophil recruitment and oxidative stress in GIT of zebrafish larvae were observed. The mechanism of the combined toxicity was revealed by transmission electron microscopy (TEM) showing the injuries of GIT, transcriptome and 16S rDNA gene sequencing showing the toxicity pathways, including oxidative phosphorylation and respiratory electron transport chain, as well as microbial community analysis showing the induced microbiota dysbiosis. In vitro tests using HCT-116 cells showed that PSNPs (10 mg/L) and Cu2+ (0.5 mg/L) increased cell death while decreasing ATP concentration and mitochondrial membrane potential after 48 h exposure. These findings may provide new insights into the combined toxicity of nanoplastics and heavy metals in the intestinal microenvironment.

Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses.

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.

Influence of electronic correlation on the valley and topological properties of VSiGeP4 monolayer.

Valley is used as a new degree of freedom for information encoding and storage. In this work, the valley and topological properties of the VSiGeP4 monolayer were studied by adjusting the U value based on first-principles calculations. The VSiGeP4 monolayer remains in a ferromagnetic ground state regardless of the change in the U value. The magnetic anisotropy of the VSiGeP4 monolayer is initially in-plane, and then turns out-of-plane with the increase in the U value. Moreover, a topological phase transition is observed in the present VSiGeP4 monolayer with the increase in U value from 0 to 3 eV, i.e., the VSiGeP4 monolayer behaves as a bipolar magnetic semiconductor, a ferrovalley semiconductor, a half-valley metal characteristic, and a quantum anomalous Hall state. The mechanism of the topological phase transition behavior of the VSiGeP4 monolayer was analyzed. It was found that the variation in U values would change the strength of the electronic correlation effect, resulting in the valley and topological properties. In addition, carrier doping was studied to design a valleytronic device using this VSiGeP4 monolayer. By doping 0.05 electrons per f.u., the VSiGeP4 monolayer with a U value of 3 eV exhibits 100% spin polarization. This study indicates that the VSiGeP4 monolayer has potential applications in spintronic, valleytronic, and topological electronic nanodevices.

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke.

Transcription factor EB (TFEB) is an important endogenous defensive protein that responds to ischemic stimuli. Acute ischemic stroke is a growing concern due to its high morbidity and mortality. Most survivors suffer from disabilities such as numbness or weakness in an arm or leg, facial droop, difficulty speaking or understanding speech, confusion, impaired balance or coordination, or loss of vision. Although TFEB plays a neuroprotective role, its potential effect on ischemic stroke remains unclear. This article describes the basic structure, regulation of transcriptional activity, and biological roles of TFEB relevant to ischemic stroke. Additionally, we explore the effects of TFEB on the various pathological processes underlying ischemic stroke and current therapeutic approaches. The information compiled here may inform clinical and basic studies on TFEB, which may be an effective therapeutic drug target for ischemic stroke.

Equivalent Input Disturbance-Based Control: Analysis, Development, and Applications.

This article reviews the concept, analysis, development, and applications of the equivalent-input-disturbance (EID) approach. First, the definition and existence of the EID are given, and the configuration of the EID estimator is provided. Next, estimation errors in the conventional EID approach are explained, and error-suppression methods are exhibited, which improve the disturbance-rejection performance. Then, this article describes how to apply the EID approach and associate challenges in dealing with nonlinearities, time delays, and uncertainties. Moreover, this article reviews some additional meaningful studies that cannot be categorized into the above-mentioned classes. Finally, some conclusions and future directions are given. The EID approach has been successfully used to suppress the influences of exogenous disturbances, nonlinearities, time delays, and uncertainties in many control systems to improve control performance and robustness. Studies can further rich the theory of the EID approach in the future, such as designing evaluation index, improving disturbance-rejection performance, developing new applications, and combining with other control theory.

Towards virtual machine scheduling research based on multi-decision AHP method in the cloud computing platform.

Virtual machine scheduling and resource allocation mechanism in the process of dynamic virtual machine consolidation is a promising access to alleviate the cloud data centers of prominent energy consumption and service level agreement violations with improvement in quality of service (QoS). In this article, we propose an efficient algorithm (AESVMP) based on the Analytic Hierarchy Process (AHP) for the virtual machine scheduling in accordance with the measure. Firstly, we take into consideration three key criteria including the host of power consumption, available resource and resource allocation balance ratio, in which the ratio can be calculated by the balance value between overall three-dimensional resource (CPU, RAM, BW) flat surface and resource allocation flat surface (when new migrated virtual machine (VM) consumed the targeted host's resource). Then, virtual machine placement decision is determined by the application of multi-criteria decision making techniques AHP embedded with the above-mentioned three criteria. Extensive experimental results based on the CloudSim emulator using 10 PlanetLab workloads demonstrate that the proposed approach can reduce the cloud data center of number of migration, service level agreement violation (SLAV), aggregate indicators of energy comsumption (ESV) by an average of 51.76%, 67.4%, 67.6% compared with the cutting-edge method LBVMP, which validates the effectiveness.

A bidirectional Mendelian randomization study investigating the causal role between gut microbiota and insomnia.

Background: It has emerged that disturbances of the gut microbiota (GM) are linked to insomnia. However, the causality of the observed associations remains uncertain. Methods: We conducted a two-sample Mendelian randomization analysis based on genome-wide association study data to explore the possible causal link between GM and insomnia. The GM data were from the MiBioGen consortium, while the summary statistics of insomnia were obtained from the FinnGen consortium R9 release data. Cochran's Q statistics were used to analyze instrumental variable heterogeneity. Results: According to the inverse variance weighted estimates, the family Ruminococcaceae (odds ratio = 1.494, 95% confidence interval:1.004-2.223, p = 0.047) and the genus Lachnospiraceae (odds ratio = 1.726, 95% confidence interval: 1.191-2.501, p = 0.004) play a role in insomnia risk. In contrast, the genus Flavonifractor (odds ratio = 0.596, 95% confidence interval: 0.374-0.952, p = 0.030) and the genus Olsenella (odds ratio = 0.808, 95% confidence interval: 0.666-0.980, p = 0.031) tended to protect against insomnia. According to the reverse MR analysis, insomnia can also alter GM composition. Instrumental variables were neither heterogeneous nor horizontal pleiotropic. Conclusion: In conclusion, our Mendelian randomization study provides evidence of a causal relationship between GM and insomnia. The identified GM may be promising gut biomarkers and new therapeutic targets for insomnia. This investigation also provides a foundation for future studies examining the influence of GM on sleep disorders beyond insomnia, with potential implications for redefining the mechanisms governing sleep regulation.

The effect of intrinsic strain on the thermal expansion behavior of Janus MoSSe nanotubes: a molecular dynamic simulation.

In this study, we conducted molecular dynamic simulations to investigate the thermal expansion behavior of Janus MoSSe nanotubes. We focused on understanding how the intrinsic strain in these nanotubes affects their thermal expansion coefficient (TEC). Interestingly, we found that Janus MoSSe nanotubes with sulfur (S) on the outer surface (MoSeS) exhibit a different intrinsic strain compared to those with selenium (Se) on the outer surface (MoSSe). In light of this observation, we explored the influence of this intrinsic strain on the TEC of the nanotubes. Our results revealed distinct trends for the TEC along the radial direction (TEC-r) and the axial direction (TEC-lx) of the MoSSe and MoSeS nanotubes. The TEC-rof MoSeS nanotubes was found to be significantly greater than that of MoSSe nanotubes. Moreover, the TEC-lxof MoSeS nanotubes was smaller than that of MoSSe nanotubes. Further analysis showed that the TEC-rof MoSeS nanotubes decreased by up to 37% as the radius increased, while that of MoSSe nanotubes exhibited a slight increase with increasing radius. On the other hand, the TEC-lxof MoSeS nanotubes increased by as much as 45% with increasing radius, whereas that of MoSSe nanotubes decreased gradually. These opposite tendencies of the TECs with respect to the radius were attributed to the presence of intrinsic strain within the nanotubes. The intrinsic strain was found to play a crucial role in inducing thermally induced bending and elliptization of the nanotubes' cross-section. These effects are considered key mechanisms through which intrinsic strain influences the TEC. Overall, our study provides valuable insights into the thermal stability of Janus nanotubes. By understanding the relationship between intrinsic strain and the thermal expansion behavior of nanotubes, we contribute to the broader understanding of these materials and their potential applications.

Causal relationship between gut microbiota and myasthenia gravis: a bidirectional mendelian randomization study.

BACKGROUND: Observational studies have demonstrated an association between gut microbiota and myasthenia gravis; however, the causal relationship between the two still lacks clarity. Our goals are to ascertain the existence of a bidirectional causal relationship between gut microbiota composition and myasthenia gravis, and to investigate how gut microbiota plays a role in reducing the risk of myasthenia gravis. METHODS: We acquired gut microbiota data at the phylum, class, order, family, and genus levels from the MiBioGen consortium (N = 18,340) and myasthenia gravis data from the FinnGen Research Project (426 cases and 373,848 controls). In the two-sample Mendelian randomization analysis, we assessed the causal relationship between the gut microbiota and myasthenia gravis. We also conducted bidirectional MR analysis to determine the direction of causality. The inverse variance weighted, mendelian randomization-Egger, weighted median, simple mode, and weighted mode were used to test the causal relationship between the gut microbiota and severe myasthenia gravis. We used MR-Egger intercept and Cochran's Q test to assess for pleiotropy and heterogeneity, respectively. Furthermore, we utilized the MR-PRESSO method to evaluate horizontal pleiotropy and detect outliers. RESULTS: In the forward analysis, the inverse-variance weighted method revealed that there is a positive correlation between the genus Lachnoclostridium (OR = 2.431,95%CI 1.047-5.647, p = 0.039) and the risk of myasthenia gravis. Additionally, the family Clostridiaceae1 (OR = 0.424,95%CI 0.202-0.889, p = 0.023), family Defluviitaleaceae (OR = 0.537,95%CI 0.290-0.995, p = 0.048), family Enterobacteriaceae (OR = 0.341,95%CI 0.135-0.865, p = 0.023), and an unknown genus (OR = 0.407,95%CI 0.209-0.793, p = 0.008) all demonstrated negative correlation with the risk of developing myasthenia gravis. Futhermore, reversed Mendelian randomization analysis proved a negative correlation between the risk of myasthenia gravis and genus Barnesiella (OR = 0.945,95%CI 0.906-0.985, p = 0.008). CONCLUSION: Our research yielded evidence of a causality connection in both directions between gut microbiota and myasthenia gravis. We identified specific types of microbes associated with myasthenia gravis, which offers a fresh window into the pathogenesis of this disease and the possibility of developing treatment strategies. Nonetheless, more studies, both basic and clinical, are necessary to elucidate the precise role and therapeutic potential of the gut microbiota in the pathogenesis of myasthenia gravis.

Excessive Sedentary Time Is Associated with Cognitive Decline in Older Patients with Minor Ischemic Stroke.

BACKGROUND: Cognitive impairment is commonly seen after acute ischemic stroke (AIS). Sedentary behaviors increase the risk of dementia among community dwelling population. OBJECTIVE: This study aims to investigate the association of sedentary behaviors with poststroke cognitive impairment among older adults with minor AIS. METHODS: This cohort study recruited 594 older subjects with minor AIS from three hospitals in China during February 1, 2016, and December 31, 2018. Participants were followed up for two years and the sedentary time per day was self-reported at the end of follow-up. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). Participants were categorized into the high and low sedentary time group according to the median sedentary time of the participants. RESULTS: At two years of follow-up, the long sedentary time group had significantly lower MMSE scores than the short sedentary time group [median, (IQR): 21 (18 to 25) versus 22 (18 to 25), p = 0.368]. The long sedentary time group had a higher speed of cognitive decline than the short sedentary time group. Excessive sedentary time was associated with a higher risk of longitudinal cognitive decline (OR: 2.267, 95% CI: 1.594 to 3.225), adjusting for age, sex, education, body mass index, APOE genotype, comorbidities, symptoms of depression, anxiety, and insomnia, baseline MMSE scores and National Institute of Health Stroke Scale scores, cognitive therapy, and TOAST ischemic stroke subtypes. CONCLUSIONS: This study identified a possible link between sedentary behaviors and longitudinal cognitive decline among older patients with minor AIS, suggesting that reducing sedentary time might be helpful for preventing poststroke dementia.

Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action.

Colorectal cancer (CRC) is the third most common malignant tumor in the world, and it is prone to recurrence and metastasis during treatment. Aerobic glycolysis is one of the main characteristics of tumor cell metabolism in CRC. Tumor cells rely on glycolysis to rapidly consume glucose and to obtain more lactate and intermediate macromolecular products so as to maintain growth and proliferation. The regulation of the CRC glycolysis pathway is closely associated with several signal transduction pathways and transcription factors including phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), myc, and p53. Targeting the glycolytic pathway has become one of the key research aspects in CRC therapy. Many phytochemicals were shown to exert anti-CRC activity by targeting the glycolytic pathway. Here, we review the effects and mechanisms of phytochemicals on CRC glycolytic pathways, providing a new method of drug development.

Natural products and mitochondrial allies in colorectal cancer therapy.

Colorectal cancer (CRC) is a globally prevalent malignancy with a high potential for metastasis. Existing cancer treatments have limitations, including drug resistance and adverse effects. Researchers are striving to develop effective therapies to address these challenges. Impressively, contemporary research has discovered that many natural products derived from foods, plants, insects, and marine invertebrates can suppress the progression, metastasis, and invasion of CRC. In this review, we conducted a comprehensive search of the CNKI, PubMed, Embase, and Web of Science databases from inception to April 2023 to evaluate the efficacy of natural products targeting mitochondria to fight against CRC. Mitochondria are intracellular energy factories involved in cell differentiation, signal transduction, cell cycle regulation, apoptosis, and tumorigenesis. The identified natural products have been classified and summarized based on their mechanisms of action. These findings indicate that natural products can induce apoptosis in colorectal cancer cells by inhibiting the mitochondrial respiratory chain, ROS elevation, disruption of mitochondrial membrane potential, the release of pro-apoptotic factors, modulation of the Bcl-2 protein family to facilitate cytochrome c release, induction of apoptotic vesicle activity by activating the caspase protein family, and selective targeting of mitochondrial division. Furthermore, diverse apoptotic signaling pathways targeting mitochondria, such as the MAPK, p53, STAT3, JNK and AKT pathway, have been triggered by natural products. Natural products such as diosgenin, allopurinol, and clausenidin have demonstrated low toxicity, high efficacy, and multi-targeted properties. Mitochondria-targeting natural products have great potential for overcoming the challenges of CRC therapy.