scMLC: an accurate and robust multiplex community detection method for single-cell multi-omics data.

Clustering cells based on single-cell multi-modal sequencing technologies provides an unprecedented opportunity to create high-resolution cell atlas, reveal cellular critical states and study health and diseases. However, effectively integrating different sequencing data for cell clustering remains a challenging task. Motivated by the successful application of Louvain in scRNA-seq data, we propose a single-cell multi-modal Louvain clustering framework, called scMLC, to tackle this problem. scMLC builds multiplex single- and cross-modal cell-to-cell networks to capture modal-specific and consistent information between modalities and then adopts a robust multiplex community detection method to obtain the reliable cell clusters. In comparison with 15 state-of-the-art clustering methods on seven real datasets simultaneously measuring gene expression and chromatin accessibility, scMLC achieves better accuracy and stability in most datasets. Synthetic results also indicate that the cell-network-based integration strategy of multi-omics data is superior to other strategies in terms of generalization. Moreover, scMLC is flexible and can be extended to single-cell sequencing data with more than two modalities.

Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.

DeepQs: Local quality assessment of cryo-EM density map by deep learning map-model fit score.

Cryogenic electron microscopy maps are valuable for determining macromolecule structures. A proper quality assessment method is essential for cryo-EM map selection or revision. This article presents DeepQs, a novel approach to estimate local quality for 3D cryo-EM density maps, using a deep-learning algorithm based on map-model fit score. DeepQs is a parameter-free method for users and incorporates structural information between map and its related atomic model into well-trained models by deep learning. More specifically, the DeepQs approach leverages the interplay between map and atomic model through predefined map-model fit score, Q-score. DeepQs can get close results to the ground truth map-model fit scores with only cryo-EM map as input. In experiments, DeepQs demonstrates the lowest root mean square error with standard method Fourier shell correlation metric and high correlation with map-model fit score, Q-score, when compared with other local quality estimation methods in high-resolution dataset (<=5 Å). DeepQs can also be applied to evaluate the quality of the post-processed maps. In both cases, DeepQs runs faster by using GPU acceleration. Our program is available at http://www.csbio.sjtu.edu.cn/bioinf/DeepQs for academic use.

Gut microbiota and intestinal immunity-A crosstalk in irritable bowel syndrome.

Irritable bowel syndrome (IBS), one of the most prevalent functional gastrointestinal disorders, is characterized by recurrent abdominal pain and abnormal defecation habits, resulting in a severe healthcare burden worldwide. The pathophysiological mechanisms of IBS are multi-factorially involved, including food antigens, visceral hypersensitivity reactions, and the brain-gut axis. Numerous studies have found that gut microbiota and intestinal mucosal immunity play an important role in the development of IBS in crosstalk with multiple mechanisms. Therefore, based on existing evidence, this paper elaborates that the damage and activation of intestinal mucosal immunity and the disturbance of gut microbiota are closely related to the progression of IBS. Combined with the application prospect, it also provides references for further in-depth exploration and clinical practice.

Elucidation of WW domain ligand binding specificities in the Hippo pathway reveals STXBP4 as YAP inhibitor.

The Hippo pathway, which plays a critical role in organ size control and cancer, features numerous WW domain-based protein-protein interactions. However, ~100 WW domains and 2,000 PY motif-containing peptide ligands are found in the human proteome, raising a "WW-PY" binding specificity issue in the Hippo pathway. In this study, we have established the WW domain binding specificity for Hippo pathway components and uncovered a unique amino acid sequence required for it. By using this criterion, we have identified a WW domain-containing protein, STXBP4, as a negative regulator of YAP. Mechanistically, STXBP4 assembles a protein complex comprising α-catenin and a group of Hippo PY motif-containing components/regulators to inhibit YAP, a process that is regulated by actin cytoskeleton tension. Interestingly, STXBP4 is a potential tumor suppressor for human kidney cancer, whose downregulation is correlated with YAP activation in clear cell renal cell carcinoma. Taken together, our study not only elucidates the WW domain binding specificity for the Hippo pathway, but also reveals STXBP4 as a player in actin cytoskeleton tension-mediated Hippo pathway regulation.

Dual-microRNA-Controlled Electrochemiluminescence Biosensor for Breast Cancer Diagnosis and Supplemental Identification of Breast Cancer Metastasis.

Breast cancer remains the most frequently diagnosed cancer globally, and the metastasis of this malignancy is the primary cause of mortality in breast cancer patients. Hence, prompt diagnosis and timely detection of metastatic breast cancer are critical for effective therapeutic intervention. Both progression and metastasis of this malignancy are closely associated with aberrant expression of specific microRNAs (miRNAs) and enzymes. To facilitate breast cancer diagnosis and concomitant identification of metastatic breast cancer, we have engineered an innovative electrochemiluminescence (ECL)-based sensing platform integrated with enzyme-free DNA amplification circuits for dual functionality. Specifically, microRNA-21 (miR-21) is employed as a biomarker for breast cancer, and miR-21 induces the quenching of the ECL signal from luminophores via a strategically designed catalytic three-hairpin assembly (CTHA) circuit. Subsequently, miR-105 levels are measured via toehold-mediated strand displacement reactions (TSDR). Here, miR-105 restores the initially quenched ECL signal, enabling the assessment of the metastatic propensity. Our experimental data demonstrate that the devised ECL biosensor offers broad linear detection ranges and low detection limits for both miR-21 and miR-105. Importantly, our novel platform was also successfully validated by using cellular and serum samples. This biosensor not only discriminates breast cancer cell lines MCF-7 and MDA-MB-231 from nonbreast cancer cells like HepG2, TPC-1, and HeLa, but it also distinguishes between malignant MCF-7 and metastatic MDA-MB-231 cells. Consequently, our novel approach holds significant promise for clinical applications and precise cancer screening.

Systematic Constructing FeOCl/BiVO4 Hetero-Interfacial Hybrid Photoanodes for Efficient Photoelectrochemical Water Splitting.

Bismuth vanadate (BiVO4), as a promising photoanode for photoelectrochemical (PEC) water splitting, suffers from poor charge separation efficiency and light absorption efficiency. Herein, iron oxychloride (FeOCl) is introduced as a novel cocatalyst simply grafted on BiVO4 to construct an integrated photoanode, enhancing PEC performance. The optimized FeOCl/BiVO4 photoanode exhibits a superior photocurrent density value of 5.23 mA cm-2 at 1.23 V versus reversible hydrogen electrode (RHE) under AM 1.5G illuminations. From experimental analysis, such high PEC performance is ascribed to the unique properties of FeOCl, facilitating charge transport, increasing light absorption efficiency, and promoting water oxidation kinetics. Density functional theory calculations further confirm that FeOCl optimizes the Gibbs free energy of H and O-containing intermediates (OOH*) during PEC processes, boosting the catalytic kinetics of PEC water splitting. This work presents FeOCl as a promising catalyst for constructing high efficient PEC water-splitting photoanodes.

PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.

BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.

Tfh cell-derived small extracellular vesicles exacerbate the severity of collagen-induced arthritis by enhancing B-cell responses.

Soluble components secreted by Tfh cells are critical for the germinal center responses. In this study, we investigated whether Tfh cells could regulate the B-cell response by releasing small extracellular vesicles (sEVs). Our results showed that Tfh cells promote B-cell differentiation and antibody production through sEVs and that CD40L plays a crucial role in Tfh-sEVs function. In addition, increased Tfh-sEVs were found in mice with collagen-induced arthritis (CIA). Adoptive transfer of Tfh cells significantly exacerbated the severity of CIA; however, the effect of Tfh cells on exacerbating the CIA process was significantly diminished after inhibiting sEVs secretion. Moreover, the levels of plasma Tfh-like-sEVs and CD40L expression on Tfh-like-sEVs in RA patients were significantly higher than those in healthy subjects. In summary, Tfh cell-derived sEVs can enhance the B-cell response, and exacerbate the procession of autoimmune arthritis.

Development of CRISPR/Cas Delivery Systems for In Vivo Precision Genome Editing.

ConspectusClustered, regularly interspaced, short palindromic repeat (CRISPR)/associated protein 9 (CRISPR/Cas9) is emerging as a powerful genome-editing tool, enabling precise and targeted modifications of virtually any genomic sequence in living cells. These technologies have potential therapeutic applications for cancers, metabolic diseases, and genetic disorders. However, several major challenges hinder the full realization of their potential. Specifically, CRISPR-Cas9 gene editors, whether delivered as plasmid DNA, mRNA/sgRNA, or ribonucleoprotein (RNP), exhibit poor membrane permeability, restricting their access to the intracellular genome, where the editing occurs. Additionally, these editors lack tissue or organ specificity, raising concerns about off-target editing at the tissue level that causes unwanted genotoxicity. Though a range of delivery carriers has been developed to deliver Cas9 editors, their effectiveness is often limited by a number of barriers at both the extracellular and intracellular levels. Moreover, the prolonged activity of Cas9 increases the risk of off-target editing at the genomic level. Therefore, it is crucial to develop efficient delivery vectors, along with molecular switches to safely regulate Cas9 activity.In this Account, we summarize our recent achievements in developing different types of materials that can efficiently deliver the plasmid DNA encoding Cas9 protein and single-guide RNA (sgRNA), or Cas9 RNP into cells to highlight the design considerations of carriers for safe and efficient delivery in vitro and in vivo. After elucidating the chemical and physical factors that are responsible for encapsulating and delivering these biomacromolecules, we further elucidate how we design the biodegradable polymeric carriers using dynamic disulfide chemistry, emphasize their safe and efficient delivery features for genome-editing biomacromolecules, and also introduce the integration of the intracellular delivery of genome-editing biomacromolecules with microneedle-based transdermal delivery to promote therapeutic genome editing for inflammatory skin disorders. Finally, we review how we exploit optical, chemical, and genetic switches to control the Cas9 activity in conjunction with targeted delivery to address the spatiotemporal specificity of gene editing in vivo and demonstrate their precision therapy against cancer and colitis treatment as proof-of-concept examples. In the final part, we will summarize the progress we have made and propose the future directions that may impact the field based on our own research outcomes.

Association of Psychosocial Risk Factors With Quality of Life and Readmissions 1 Year After LVAD Implantation.

BACKGROUND: Among patients with advanced heart failure (HF), treatment with a left ventricular assist device (LVAD) improves health-related quality of life (HRQOL). We investigated the association between psychosocial risk factors, HRQOL and outcomes after LVAD implantation. METHODS: A retrospective cohort (n = 9832) of adults aged ≥ 19 years who received durable LVADs between 2008 and 2017 was identified by using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Patients were considered to have psychosocial risk factors if ≥ 1 of the following were present: (1) substance abuse; (2) limited social support; (3) limited cognitive understanding; (4) repeated nonadherence; and (5) major psychiatric disease. Multivariable logistic and linear regression models were used to evaluate the association between psychosocial risk factors and change in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 scores from baseline to 1 year, persistently poor HRQOL (KCCQ-12 score < 45 at baseline and 1 year), and 1-year rehospitalization. RESULTS: Among the final analytic cohort, 2024 (20.6%) patients had ≥ 1 psychosocial risk factors. Psychosocial risk factors were associated with a smaller improvement in KCCQ-12 scores from baseline to 1 year (mean ± SD, 29.1 ± 25.9 vs 32.6 ± 26.1; P = 0.015) for a difference of -3.51 (95% confidence interval [CI]: -5.88 to -1.13). Psychosocial risk factors were associated with persistently poor HRQOL (adjusted odds ratio [aOR] 1.35, 95% confidence interval [CI] 1.04-1.74), and 1-year all-cause readmission (adjusted hazard ratio [aHR] 1.11, 95% CI 1.05-1.18). Limited social support, major psychiatric disorder and repeated nonadherence were associated with persistently poor HRQOL, while major psychiatric disorder was associated with 1-year rehospitalization. CONCLUSION: The presence of psychosocial risk factors is associated with lower KCCQ-12 scores and higher risk for readmission at 1 year after LVAD implantation. These associations are statistically significant, but further research is needed to determine whether these differences are clinically meaningful.

Multiple plateaus of high-sideband generation from Floquet matters.

We theoretically report that high-order sideband generation (HSG) from Floquet matters driven by a strong terahertz light while engineered by weak infrared light can achieve multiple plateau HSG. The Floquet-engineering systems exhibit distinctive spectroscopic characteristics that go beyond the HSG processes in field-free band-structure systems. The spatial-temporal dynamics analyses under Floquet-Bloch and time-reversal-symmetry theories clarify the spectra and its odd-even characteristics in the HSG spectrum. Our work demonstrates the HSG of Floquet matters via Floquet engineering and indicates a promising way to extract Floquet material parameters in future experiments.

The potential role of hydrogen sulfide in regulating macrophage phenotypic changes via PINK1/parkin-mediated mitophagy in sepsis-related cardiorenal syndrome.

OBJECTIVE: Sepsis is one of major reasons of cardiorenal syndrome type 5 (CRS-5), resulting in irreversible tissue damage and organ dysfunction. Macrophage has been demonstrated to play key role in the pathophysiology of sepsis, highlighting the need to identify therapeutic targets for modulating macrophage phenotype in sepsis. METHODS AND RESULTS: In this study, a rapid-releasing hydrogen sulfide (H2S) donor NaSH, and a slow-releasing H2S compound S-propargyl-cysteine (SPRC) which is derived from garlic, have been studied for the immune-regulatory effects on macrophages. The NaSH and SPRC showed the potential to protect the heart and kidney from tissue injury induced by LPS. The immunohistochemistry of F4/80+ revealed that the infiltration of macrophages in the heart and kidney tissues of LPS-treated mice was reduced by NaSH and SPRC. In addition, in the LPS-triggered inflammatory cascade of RAW264.7 macrophage cells, NaSH and SPRC exhibited significantly inhibitory effects on the secretion of inflammatory cytokines, production of reactive oxygen species (ROS), and regulation of the macrophage phenotype from M1-like to M2-like. Moreover, autophagy, a crucial process involved in the elimination of impaired proteins and organelles during oxidative stress and immune response, was induced by NaSH and SPRC in the presence of LPS stimulation. Consequently, there was an increase in the number of mitochondria and an improvement in mitochondrial membrane potential. This process was mainly mediated by PINK1/Parkin pathway mediated mitophagy. DISCUSSION: These results demonstrated that the immunoregulatory effects of H2S donors were through the PINK1/Parkin-mediated mitophagy pathway. Overall, our study provided a new therapeutic direction in LPS-induced cardiorenal injury.

Supramolecular Genome Editing: Targeted Delivery and Endogenous Activation of CRISPR/Cas9 by Dynamic Host-Guest Recognition.

We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor-specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off-target editing in healthy tissues and non-targeted organs. As the metabolism of polyamines is dysregulated in a wide range of disorders, this study offers a supramolecular approach to precisely control CRISPR/Cas9 functions under particular pathological contexts.

Cryo-EM image alignment: From pair-wise to joint with deep unsupervised difference learning.

Cryo-electron microscopy (cryo-EM) single-particle analysis is a revolutionary imaging technique to resolve and visualize biomacromolecules. Image alignment in cryo-EM is an important and basic step to improve the precision of the image distance calculation. However, it is a very challenging task due to high noise and low signal-to-noise ratio. Therefore, we propose a new deep unsupervised difference learning (UDL) strategy with novel pseudo-label guided learning network architecture and apply it to pair-wise image alignment in cryo-EM. The training framework is fully unsupervised. Furthermore, a variant of UDL called joint UDL (JUDL), is also proposed, which is capable of utilizing the similarity information of the whole dataset and thus further increase the alignment precision. Assessments on both real-world and synthetic cryo-EM single-particle image datasets suggest the new unsupervised joint alignment method can achieve more accurate alignment results. Our method is highly efficient by taking advantages of GPU devices. The source code of our methods is publicly available at "http://www.csbio.sjtu.edu.cn/bioinf/JointUDL/" for academic use.

Spindle Monitor: A Tool for Real-Time Assessment and Concurrent Treatment of Postoperative Tumor Prognosis.

Cancer surgery remains a mainstay in clinical treatment. However, the efficacy of subsequent therapies largely depends on the precise evaluation of postoperative prognoses, underscoring the critical need for a comprehensive and accurate assessment of surgical outcomes. Nanoprobes targeting tumors offer a promising solution for visual prognostic assessment. In this study, we developed a "Spindle Monitor" system, designated as APPADs (Au NBPs@PDA-pep-AS1411-Dox), composed of core-shell nanoparticles. The core was made up of gold nanobipyramids (Au NBPs), coated with polydopamine (PDA), and subsequently loaded with peptide chains, AS1411, and doxorubicin (Dox). Upon deployment in the acidic tumor microenvironment (TME), APPADs released substantial amounts of Dox, initiating the apoptotic process. This triggered the activity of caspase-3, which is a crucial executor in the apoptotic pathway. Consequently, DEVD, a specific recognition site for caspase-3, was cleaved, enabling the disconnection of FITC-conjugated peptide chains and the recovery of fluorescence. Through assessing this fluorescence imaging effect, local laser irradiation could be precisely guided to the postoperative site, facilitating a synergistic combination of photothermal therapy and chemotherapy. Specifically, our "Spindle Monitor" APPADs had been validated to achieve accurate fluorescence imaging in vitro and in vivo, which demonstrated its potential value as a versatile tool for evaluating postoperative prognosis in surgical treatments, such as thyroid cancer, and assessing chemotherapy efficacy in difficult cases, like late-stage osteosarcoma. This promising tool lays a good foundation for development in visual prognosis evaluation after tumor surgery.

Insight on genetic features prevalent in five Ipomoea species using comparative codon pattern analysis reveals differences in major codons and reduced GC content at the 5' end of CDS.

Ipomoea plants possess important commercial, medicinal, and ornamental value. Molecular and morphological studies have confirmed that most species of this genus exhibit similar phenotypes but complex phylogenetic relationships. To date, limited information is available on these evolutionary relationships. In this study, systematic analysis of diverse species from Ipomoea was used to elucidate the relationships in this genus. To this end, we employed the concept of codon usage bias (CUB) to analyze the codon usage bias of five Ipomoea species such as effective number of codons (ENC) and GC content at the third synonym codon position (GC3s). Three types of plots including ENC-GC3s, parity rule 2 (PR2) and neutrality plots were employed to discover the factors determining CUB, and the frequency of hydrogen bonds and nucleotide were calculated to dissect changes in GC content at the 5'-end of the coding sequence. Our results showed little distinctness in CUB among the five species, with a reduction of hydrogen bonds content at the 5'-end (with similar changes in cytosines). In addition, optimal codons of Ipomoea aquatica ended with G or C, different from those of the other four species, which ended in A or T. These results may be useful for exploring the evolutionary relationships among this group, and for understanding the reasons for the variation among Ipomoea species.

Design, Synthesis and Characterization of Palladium-Functionalized Covalent Organic Framework and Its Application as Heterogeneous Catalysis for C-H Arylation of Azoles.

A novel triazine-based covalent organic framework (TFPT-Bz COF) has been constructed by the condensation of 2,4,6-tris(5-formyl-2-pyridinoxy)-1,3,5-triazine (TFPT) and benzidine (BZ) with deep eutectic solvent (DES) as the reaction medium. After the introduction of Pd ions through strong coordination to TFPT-Bz COF matrix, the constructed TFPT-Bz COF/Pd composite exhibited excellent catalytic activity for C-H arylation of azoles with aryl halides in 2-methyltetrahydrofuran. The protocol allows the arylation of a variety of substituted azoles with diverse aryl halides in high to excellent yield. Moreover, the TFPT-Bz COF/Pd catalyst can be recycled several times without significantly reducing its activity.

The role of gut microbiota and metabolites in regulating the immune response in drug-induced enteritis.

Drug-induced enteritis is an inflammatory disease changing in the morphology and function of the intestine as a result of medicine damage. With the increase in drug abuse in recent years, the incidence of drug-associated enteritis accordingly rises and becomes an important disease affecting the health and life quality of patients. Hence, elucidating the pathogenesis of drug-induced enteritis and finding cost-effective diagnostic and therapeutic tools have become current research focuses. The gut microbiota and metabolites regulate the immune response, playing a key role in the maintenance of homeostasis in the intestine. Numerous studies have found that many medicines can induce intestinal flora disorders, which are closely related to the development of drug-induced enteritis. Therefore, this paper analyses the role of gut microbiota and metabolites in regulating the immune response, and provides basic research direction and clinical reference strategies for drug-induced enteritis, taking into account the existing applications and perspectives.

Uncovering the bridging role of slow atoms in unusual caged dynamics and ß-relaxation of binary metallic glasses.

The origin of ß-relaxation in metallic glasses is still not fully understood, and the guidance of slow atoms for caged dynamics and ß-relaxation is rarely mentioned. Using molecular dynamics simulations, we reveal the bridging role of slow atoms on unusual caged dynamics and ß-relaxation. In the stage of unusual caged dynamics, slow atoms are bounded by neighboring atoms. It is difficult for the slow atoms to break the cage, producing more high-frequency vibration, which causes more atoms to jump out of the cage randomly in the next stage. Precisely, the movement of the slow atoms changes from individual atoms vibrating inside the cage and gradually breaking out of the cage into a string-like pattern. The string-like collective atomic jumps cause decay of the cages, inducing ß-relaxation. This situation generally exists in binary systems with the large atomic mass difference. This work offers valuable insights for understanding the role of slow atoms in unusual caged dynamics and ß-relaxation, complementing studies on the origin of ß-relaxation in metallic glasses and their glass-forming liquids.