Advances in fecal microbiota transplantation for the treatment of diabetes mellitus.

Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.

Role of Helicobacter pylori virulence factors and alteration of the Tumor Immune Microenvironment: challenges and opportunities for Cancer Immunotherapy.

Various forms of malignancies have been linked to Helicobacter pylori. Despite advancements in chemotherapeutic and surgical approaches, the management of cancer, particularly at advanced stages, increasingly relies on the integration of immunotherapy. As a novel, safe therapeutic modality, immunotherapy harnesses the immune system of the patient to treat cancer, thereby broadening treatment options. However, there is evidence that H. pylori infection may influence the effectiveness of immunotherapy in various types of cancer. This association is related to H. pylori virulence factors and the tumor microenvironment. This review discusses the influence of H. pylori infection on immunotherapy in non-gastrointestinal and gastrointestinal tumors, the mechanisms underlying this relationship, and directions for the development of improved immunotherapy strategies.

In Vitro Antibacterial Activity of a Novel Acid-Activated Antimicrobial Peptide against Streptococcus mutans.

BACKGROUND: Dental caries is an oral disease associated with infection by microbial biofilm. The metabolic activity of cariogenic bacteria results in a pH decrease in the plaque biofilm, causing tooth demineralization. This acidic environment favors the growth of cariogenic bacteria that are highly resistant to strong acids, which, in turn, produce more acid resulting in a further decrease in the pH of the plaque biofilm. Therefore, the strategy of utilizing the acidic dental plaque microenvironment to prevent and treat dental caries has become a hot research topic in recent years, such as the development of pH-sensitive drug delivery systems. AIMS: Design of a new acid-activated antibacterial peptide. OBJECTIVES: To design and synthesis an acid targeted antimicrobial peptide with the GWHHFFHFFHFF sequence. METHODS: Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) testing confirmed its antibacterial activity. Propidium iodide (PI) staining was used to detect nucleic acid leakage. Determination of anti-biofilm activity by biofilm inhibition assay. A phototoxicity study confirmed the phototoxicity of PPIX-P12. RESULTS: MIC and MBC testing confirmed that P12 possessed acid-activated anti-Streptococcus mutans activity. Bactericidal kinetic experiments and propidium iodide (PI) staining experiments showed that P12 killed planktonic S. mutans UA159 cells leading to the leakage of nucleic acids in the acidic medium. Moreover, P12 showed acid-activated anti-biofilms at the early and mature biofilm stages. P12 was conjugated with the phototherapeutic agent protoporphyrin IX (PpIX) to construct the protoporphyrin derivative PpIX-P12. In vitro experiments revealed that PpIX-P12 displayed better antibacterial activity in pH 5.5 medium than in pH 7.2 medium. CONCLUSION: In conclusion, we designed an acid-activated AMP, which had no antimicrobial activity at neutral pH, but had antimicrobial activity at an acidic pH.

A Hybrid Antimicrobial Peptide Targeting Staphylococcus aureus with a Dual Function of Inhibiting Quorum Sensing Signaling and an Antibacterial Effect.

Community-associated methicillin-resistant Staphylococcus aureus (MRSA) is now a major cause of bacterial infection. Antivirulence therapy does not stimulate evolution of a pathogen toward a resistant phenotype, providing a novel method to treat infectious diseases. Here, we used a cyclic peptide of CP7, an AIP-III variant that specifically inhibited the virulence and biofilm formation of Staphylococcus aureus (S. aureus) in a nonbiocidal manner, to conjugate with a broad-spectrum antimicrobial peptide (AMP) via two N-termini to obtain a hybrid AMP called CP7-FP13-2. This peptide not only specifically inhibited the production of virulence of S. aureus at low micromolar concentrations but also killed S. aureus, including MRSA, by disrupting the integrity of the bacterial cell membrane. In addition, CP7-FP13-2 inhibited the formation of the S. aureus biofilm and showed good antimicrobial efficacy against the S. aureus-infected Kunming mice model. Therefore, this study provides a promising strategy against the resistance and virulence of S. aureus.

Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway.

BACKGROUND: Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC. AIM: To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice. METHODS: A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing. RESULTS: The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of Akkermansia decreased, and Lactobacillus became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. Akkermansia were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia. Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with Akkermansia included Aqp4, Clca4a, Dpm3, Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 (|R| > 0.9, P < 0.01). CONCLUSION: FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. Akkermansia bear great therapeutic potential for colitis.

Experimental impacts of grazing on grassland biodiversity and function are explained by aridity.

Grazing by domestic herbivores is the most widespread land use on the planet, and also a major global change driver in grasslands. Yet, experimental evidence on the long-term impacts of livestock grazing on biodiversity and function is largely lacking. Here, we report results from a network of 10 experimental sites from paired grazed and ungrazed grasslands across an aridity gradient, including some of the largest remaining native grasslands on the planet. We show that aridity partly explains the responses of biodiversity and multifunctionality to long-term livestock grazing. Grazing greatly reduced biodiversity and multifunctionality in steppes with higher aridity, while had no effects in steppes with relatively lower aridity. Moreover, we found that long-term grazing further changed the capacity of above- and below-ground biodiversity to explain multifunctionality. Thus, while plant diversity was positively correlated with multifunctionality across grasslands with excluded livestock, soil biodiversity was positively correlated with multifunctionality across grazed grasslands. Together, our cross-site experiment reveals that the impacts of long-term grazing on biodiversity and function depend on aridity levels, with the more arid sites experiencing more negative impacts on biodiversity and ecosystem multifunctionality. We also highlight the fundamental importance of conserving soil biodiversity for protecting multifunctionality in widespread grazed grasslands.

Exploring the alteration of gut microbiota and brain function in gender-specific Parkinson's disease based on metagenomic sequencing.

Background: The role of the microbiota-gut-brain axis in Parkinson's disease (PD) has received increasing attention. Although gender differences are known to an essential role in the epidemiology and clinical course of PD, there are no studies on the sex specificity of the microbiota-gut-brain axis in the development and progression of PD. Methods: Fresh fecal samples from 24 PD patients (13 males, 11 females) were collected for metagenomic sequencing. The composition and function of the gut microbiota were analyzed by resting-state functional magnetic resonance imaging (fMRI). Gender-dependent differences in brain ALFF values and their correlation with microbiota were further analyzed. Results: The relative abundance of Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname was increased in male PD patients. LEfse analysis showed that Verrucomicrobial, Akkermansiaceae, and Akkermansia were dominant in the males. In female patients, the relative abundance of Propionicicella was decreased and Escherichia, Escherichia_coli, and Lachnospiraceae were predominant. The expression of the sesquiterpenoid and triterpenoid biosynthesis pathways was increased in male PD patients and was statistically different from females. Compared to the Male PD patients, female patients showed decreased ALFF values in the left inferior parietal regions, and the relative abundance of Propionivibrio was positively correlated with the regional ALFF values. Conclusion: Our study provides novel clinical evidence of the gender-specific relationship between gut microbiota alterations and brain function in PD patients, highlighting the critical role of the microbiota-gut-brain axis in gender differences in PD.

Fabrication and Characterization of a High-Strength Polyimide/Thermoplastic Polyurethane Composite Aerogel with Hydrophobicity and Low Thermal Conductivity.

Polyimide (PI) aerogel has surfaced in research and development as a result of its heat resistance, flame retardancy, and low dielectric constant. However, it is still a challenge to reduce the thermal conductivity while improving its mechanical strength and retaining hydrophobicity. Herein, the PI/thermoplastic polyurethane (TPU) composite aerogel was synthesized by coupling TPU with PI via a novel method of chemical imidization combined with freeze-drying technology. With this technique, PI aerogel with excellent comprehensive performance is produced. Interestingly, the volume shrinkage of the composite aerogel decreased from 24.14 to 5.47%, which leads to low density (0.095 g/cm3) and elevated porosity (92.4%). In addition, strong mechanical strength (1.29 MPa) and high hydrophobicity (123.6°) were achieved. More importantly, PI/TPU composite aerogel demonstrated a low thermal conductivity of 29.51 mW m-1 K-1 at ambient temperature. Therefore, PI/TPU composite aerogel can be a promising material for hydrophobic and thermal insulation applications.

Gut microbiota alterations in children and their relationship with primary immune thrombocytopenia.

Introduction: Gut microbiota reportedly play a critical role in some autoimmune diseases by maintaining immune homeostasis. Only a few studies have examined the correlation between gut microbiota and the onset of primary immune thrombocytopenia (ITP), especially in children. The purpose of this study was to investigate changes in the composition and diversity of the fecal microbiota of children with ITP, as well as the correlation between such microbiota and the onset of ITP. Methods: Twenty-five children newly diagnosed with ITP and 16 healthy volunteers (controls) were selected for the study. Fresh stool samples were collected to identify changes in the composition and diversity of gut microbiota as well as for potential correlation analysis. Results: In ITP patients, the phyla that were most frequently encountered were Firmicutes (54.3%), followed by Actinobacteria (19.79%), Bacteriodetes (16.06%), and Proteobacteria (8.75%). The phyla that were predominantly found in the controls were, Firmicutes (45.84%), Actinobacteria (40.15%), Bacteriodetes (3.42%), and Proteobacteria (10.23%). Compared with those of the controls, the proportions of Firmicutes and Bacteriodetes in the gut microbiota of ITP patients were increased while the proportions of Actinobacteria and Proteobacteria were decreased. Furthermore, gut microbiota in ITP patients varied by age group, showed specific changes in diversity, and were correlated with antiplatelet antibodies. IgG levels were significantly positively correlated with Bacteroides (P<0.01). Conclusions: The gut microbiota of children with ITP are imbalanced, as shown by the increase in Bacteroidetes, which was positively correlated with IgG. Thus gut microbiota may contribute to ITP pathogenesis via IgG. Clinical Trial Registration: The clinical trial were registered and approved by the Institutional Review Committee of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University. Ethics number KY-2023-106-01.

Exploration of the shared pathways and common biomarker PAN3 in ankylosing spondylitis and ulcerative colitis using integrated bioinformatics analysis.

Background: Ulcerative colitis (UC) is a chronic autoimmune-related disease that causes inflammation of the intestine. Ankylosing spondylitis (AS) is a common extraintestinal complication of UC involving the sacroiliac joint. However, the pathogenesis of AS secondary to UC has not been studied. This study aimed to investigate the shared pathways and potential common biomarkers of UC and AS. Methods: Microarray data downloaded from the Gene Expression Omnibus (GEO) database were used to screen differentially expressed genes (DEGs) in the UC and AS datasets. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules related to UC and AS. Shared genes were then further analyzed for functional pathway enrichment. Next, the optimal common biomarker was selected using SVM-RFF and further validated using two independent GEO datasets. Finally, immune infiltration analysis was used to investigate the correlation of immune cell infiltration with common biomarkers in UC and AS. Results: A total of 4428 and 2438 DEGs in UC and AS, respectively, were screened. Four modules were identified as significant for UC and AS using WGCNA. A total of 25 genes overlapped with the strongest positive and negative modules of UC and AS. KEGG analysis showed these genes may be involved in the mitogen-activated protein kinase (MAPK) signaling pathway. GO analysis indicated that these genes were significantly enriched for RNA localization. PAN3 was selected as the optimal common biomarker for UC and AS. Immune infiltration analysis showed that the expression of PAN3 was correlated with changes in immune cells. Conclusion: This study first explored the common pathways and genetic diagnostic markers involved in UC and AS using bioinformatic analysis. Results suggest that the MAPK signaling pathway may be associated with both pathogeneses and that PAN3 may be a potential diagnostic marker for patients with UC complicated by AS.

Cepharanthine Alleviates DSS-Induced Ulcerative Colitis via Regulating Aconitate Decarboxylase 1 Expression and Macrophage Infiltration.

Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.

Changes in plant community assembly from patchy degradation of grasslands and grazing by different-sized herbivores.

Grassland degradation caused by increases in livestock grazing threatens a variety of ecosystem services. Understanding changes in plant community assembly during the process of grassland degradation in the presence of grazing is important to help restore degraded grasslands worldwide but has received little attention thus far. The grassland degradation process is typified by heterogeneous degradation, that is, gradual formation of degraded patches (hereafter "patchy degradation"). Here, we experimentally examined the effects of herbivore grazing and patchy degradation on plant community assembly using nine pairs of non-degraded (intact) and patch-degraded (fragmented) grasslands subject to grazing by different-sized herbivores (i.e., NG, no grazing; SG, sheep grazing; CG, cattle grazing) over 4 years. Using a null-model approach, we estimated the relative magnitude of deterministic processes of community assembly by comparing the observed and expected ß-diversity. We found that in the absence of herbivore grazing, deterministic processes played a greater role in community assembly, regardless of whether patchy degradation had occurred. However, the deterministic processes resulted in plant communities being more spatially similar in non-degraded grasslands while being more dissimilar in patchy degraded grasslands. Compared with non-degraded grasslands, species with strong competitive abilities (i.e., Leymus chinensis) were less dominant in patchy degraded grasslands, indicating relaxed competition and a reduced role of species interactions over plant communities. Instead, patchy degradation added the role of environmental variables over plant communities. SG consistently promoted more stochastic plant community assembly in both non-degraded and patch-degraded grasslands, while CG promoted more stochastic plant community assembly only in the non-degraded state, having no effect in the patch-degraded state. Our study offers important insights into changes in plant community assembly during ongoing patch-degradation of grasslands, indicating the role of increased environmental filtering of soil and reduced species interactions in driving plant community dynamics with increasing grassland patchy degradation. We also uncovered an herbivore species-specific effect on plant community assembly during the process of grassland degradation, which will better inform and improve future grassland restoration planning efforts.

Land use intensification alters the relative contributions of plant functional diversity and soil properties on grassland productivity.

Understanding the mechanisms of grassland productivity variation is critical for global carbon cycling and climate change mitigation. Heretofore, it is unknown how different environmental factors drive small-scale spatial variation in productivity, and whether land use intensification, one of the most important global changes, can regulate the processes that drive productivity change. Here we performed an 18-year exclosure experiment across six sites with high-intensity mowing/grazing history in northern China to examine the effects of land use intensification on plant functional diversity, soil properties, and their relative contributions to above-ground net primary productivity (ANPP). We found that plant functional diversity and soil properties contributed to the variation in ANPP both independently and equally in enclosed grasslands (plant diversity: 20.6%; soil properties: 19.5%). Intensive land use significantly decreased the Rao's quadratic entropy (RaoQ) and community-weighted mean value (CWM) of plant height, and further suppressed the contributions of plant functional diversity to ANPP. In contrast, intensive land use increased soil available N, P, pH, electrical conductivity, and homogeneity of soil available P, and strengthened their contributions to ANPP (31.5%). Our results indicate that high-intensity land use practices in grasslands decrease the role of plant functional diversity, but strengthen the effects of soil properties on productivity. We, therefore, suggest that plant functional diversity can be used effectively to boost productivity in undisturbed grasslands, while soil properties might be a more critical consideration for grassland management in an areas with increased land use.

Lung adenocarcinoma relapse with emerging EGFR mutation following complete response of small cell lung cancer warrants routine re-biopsy: A case report.

Transformation of small cell lung cancer (SCLC) to lung adenocarcinoma (LUAD) is rarely reported. Here, we report a case initially presented with SCLC and was diagnosed as LUAD when the lesion relapsed at the same site. A 56-year-old patient with SCLC who received etoposide and cisplatin chemotherapy combined with radiotherapy achieved a complete radiological response. After 28 months of stable disease, a computed tomography scan revealed a new lesion at the same site as the primary tumor. Pathological examination suggested a LUAD with an emerging EGFR exon 19 deletion. The patient was then treated with icotinib and achieved a near-complete radiological response. Nineteen months later, the patient developed resistance caused by EGFR T790M mutation and received treatment with osimertinib. At the last follow-up in January 2022, the patient was symptom-free. This case warrants re-biopsy and genetic testing as a routine operation when SCLC relapses at the same site as the primary tumor for an extended period, and prospective investigation is required.

The S40 family members delay leaf senescence by promoting cytokinin synthesis.

Leaf senescence is regulated by both endogenous hormones and environmental stimuli in a programmed and concerted way. The members of the S40 family have been reported to play roles in leaf senescence. Here we identified an S40 family member, CiS40-11, from Caragana intermedia. Phylogenetic analysis revealed that the CiS40-11 protein had the highest identity with AtS40-5 (AT1G11700) and AtS40-6 (AT1G61930) of Arabidopsis thaliana. CiS40-11 was highly expressed in leaves and was down-regulated after dark treatment. The subcellular localization analysis showed that CiS40-11 was a cytoplasm-nucleus dual-localized protein. Leaf senescence was delayed in both the CiS40-11 overexpressed A. thaliana and its transiently expressed C. intermedia. Transcriptomic analysis and endogenous hormones assay revealed that CiS40-11 inhibited leaf senescence via promoting the biosynthesis of cytokinins by blocking AtMYB2 expression in the CiS40-11 overexpression lines. Furthermore, overexpression of either AtS40-5 or AtS40-6 showed similar phenotype as the CiS40-11 overexpressing lines, while in the ats40-5a or ats40-6a mutants, the AtMYB2 expression was increased and their leaves exhibited a premature senescence phenotype. These results provide a new molecular mechanism of the S40 family in leaf senescence regulation of plants.

Carbon Aerogels as Electrocatalysts for Sustainable Energy Applications: Recent Developments and Prospects.

Carbon aerogel (CA) based materials have multiple advantages, including high porosity, tunable molecular structures, and environmental compatibility. Increasing interest, which has focused on CAs as electrocatalysts for sustainable applications including oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and CO2 reduction reaction (CO2RR) has recently been raised. However, a systematic review covering the most recent progress to boost CA-based electrocatalysts for ORR/OER/HER/CO2RR is now absent. To eliminate the gap, this critical review provides a timely and comprehensive summarization of the applications, synthesis methods, and principles. Furthermore, prospects for emerging synthesis, screening, and construction methods are outlined.

Konjac glucomannan/cellulose nanofibers composite aerogel supported HKUST-1 for CO2 adsorption.

Biomass aerogels are attractive in various applications owing to their inherent advantages of renewability, biodegradability and eco-friendly. Herein, a novel composite aerogel of konjac glucomannan (KGM)/TEMPO-oxidized cellulose nanofibers (TOCNF)@HKUST-1 (KTA@HKUST-1) is prepared through a facile vacuum impregnation method combined with the directional freeze-drying process, which using KGM and TOCNF as raw materials. The structural analyses disclose that the KTA@HKUST-1 has a hierarchical porosity, in which HKUST-1 can provide micropores for adsorption, while the meso-/macropores from KTA act as high-speed channels to improve diffusion and mass transfer rate to transport CO2 components into the micropores of HKUST-1. The experiment results of KTA@HKUST-1-10 (KTA@H10) show that the CO2 adsorption capacity can reach 3.50 mmol·g-1 at 1 bar and 298 K, and the adsorption capacity retention rate as high as 91.43% after 7 cycles. In addition, the CO2/N2 adsorption selectivity of KTA@H10 can reach 18.42, which has an excellent potential for selective CO2 adsorption.

Positive Correlation of Peripheral CD8+ T Lymphocytes with Immune-Related Adverse Events and Combinational Prognostic Value in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8+ T lymphocytes at baseline was the independent risk factor for the onset of irAEs (p = 0.008). A higher level of CD8+ T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, p < 0.001) and OS (27.9 months vs. 11.7 months, p = 0.014). Furthermore, patients who had higher baseline CD8+ T lymphocytes and experienced irAEs had a longer PFS (18.4 months vs. 2.2 months, p < 0.001) and OS (32.8 months vs. 9.0 months, p = 0.001) than those who had lower CD8+ T lymphocytes and no irAEs. Our study highlights the value of baseline peripheral CD8+ T lymphocytes as a predictive factor for irAEs in advanced NSCLC patients receiving ICIs. In addition, patients who have higher baseline CD8+ T lymphocytes and experience irAEs would have a superior PFS and OS.

Cepharanthine ameliorates dextran sulphate sodium-induced colitis through modulating gut microbiota.

Cepharanthine (CEP) is an active alkaloid isolated from Stephania Cepharantha Hayata. It is reported that the anti-inflammatory properties of CEP could be employed to treat a variety of diseases. In this study, we first found that CEP ameliorates ulcerative colitis (UC) induced by DSS. The effect of CEP on gut microbiota was further evaluated by 16S rRNA gene sequencing, antibiotic pretreatment and faecal microbiota transplantation (FMT). Results showed that the abundances of gut microbiota, such as Romboutsia, Turicibacter and Escherichia-Shigella (especially Romboutsia), were significantly reduced after CEP treatment. Additionally, we explored the mechanisms of CEP by a strategy integrating transcriptomics with network pharmacology. The transcriptome data confirmed that CEP functioned through cytokine and cytokine receptor pathways. The expression levels of 10 pro-inflammatory hub genes (such as CXCL1, CXCL9, CCL7) were positively correlated with the abundance of Romboutsia. Our data identified Romboutsia as a potential pathobiont in UC. Collectively, we confirmed that CEP relieved colon inflammation by modulating gut microbiota and pro-inflammatory cytokine expression. CEP can be adopted to design novel effective therapeutic strategies for UC.

The risk of dementia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Growing evidence indicates that inflammatory bowel disease (IBD) and dementia share similar pathological mechanisms, but no consensus has yet emerged on the effect that IBD and dementia are associated. To explore such a possible correlation, we summarize herein the epidemiological evidence. We subject relevant studies to meta-analysis. METHODS: We comprehensively searched Pubmed and Embase for relevant articles published to Dec 2021. The pooled risk ratio (RR) with the 95% confidence interval (CI) was used to estimate the effect; we calculated the generic inverse variance using a random-effects model. RESULTS: Seven studies involving 65,454 patients with dementia were included in the meta-analysis. The overall risk of dementia in IBD patients was significantly higher than that in the general population (risk ratio [RR], 1.35; 95% confidence interval [CI], 1.08-1.68; P = 0.008). The results of subgroup analyses were consistent with the overall results. The risk of Alzheimer's disease was higher in IBD patients (RR = 2.79, 95% CI = 1.1, 7.04; P < 0.001). CONCLUSIONS: Our results revealed that IBD may be a potential risk indicator for dementia.