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The neighborhood effect has become an important framework with which to study the mechanisms that maintain the coexistence of tree species. Phylogenetic relatedness among neighboring plants directly affects species coexistence and the maintenance of tree diversity. And some studies have reported that seedling performance is negatively correlated with phylogenetic relatedness, which termed phylogenetic negative density dependence. Soil-borne fungal pathogens affected seedling performance of phylogenetically related host species, i.e., phylogenetic Janzen-Connell effect. Seedlings may be particularly vulnerable to habitat and neighbor characteristics. Although previous studies have demonstrated the influence of neighborhood effects, phylogenetic relatedness, and habitat filtering on seedling survival, growth, and mortality, the effect of variation in these factors on seedling abundance remains unclear. To address this question, we used a 4-ha (200 m × 200 m) and monitored four-year (2020-2023) seedling dataset from a mid-montane humid evergreen broad-leaved subtropical forest in the Gaoligong Mountains, Yunnan, Southwestern China, and which consisted of 916 seedlings belonging to 56 species. The results of generalized linear mixed models showed no significant effect of conspecific adult neighbors on seedling abundance at any of the intervals evaluated. In contrast, we found evidence of phylogenetic distance density dependence in the forests of the Gaoligong Mountains. Specifically, there was a significant positive effect of the relative average phylogenetic distance between heterospecific adult neighbors and focal seedlings on focal seedling abundance in 2020; however, the relative average phylogenetic distance between heterospecific seedling neighbors and focal seedlings had a significant negative effect on seedling abundance over the four-year period (2020-2023). Among the habitat factors, only light (canopy opening) had a negative effect on seedling abundance in all four years. Light resources may be a limiting factor for seedlings, and determine seedling dynamics in subtropical forests. Overall, our results demonstrated that phylogenetic density dependence and habitat filtering affected subtropical seedling abundance. Our findings provide new evidence of the impact of phylogenetic density dependence on seedling abundance in a subtropical mid-montane humid evergreen broad-leaved forest and highlight the need to incorporate the neighborhood effect, phylogenetic relatedness, and habitat factors in models assessing seedling abundance.

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Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, thrombocytopenia, and bleeding, however, its treatment options are limited. In this study, a kind of active component, chlorogenic acid compounds (CGAs) from sweetpotato leaves was extracted out to explore its medicinal value and provide novel therapeutic strategies for the treatment of ITP. CGAs was isolated by ionic liquids-ultrasound (IL-UAE), which contains six isomers of chlorogenic acid with total purity of 95.69%. The thrombopoietic effect and mechanism of CGAs were investigated using in silico prediction and experimental validation. The changes of HEL cells morphology in volume and the increase in the total cell percentage of polyploid cells indicated that CGAs could promote megakaryocyte differentiation. Meanwhile, CGAs could promote platelet formation in a murine model of ITP, which was established by injection of antiplatelet antibody. Further quantitative proteomics analysis and Western blot verification revealed that CGAs could activate PI3K/AKT signaling pathway, which confirmed the mechanism prediction. It suggested that CGAs may provide a novel therapeutic strategy that relies on the PI3K/AKT pathway to facilitate megakaryocyte differentiation and platelet production.

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Robustness and environmental adaptability are crucial for molybdenum disulfide (MoS2) films to minimize friction and wear in industrial applications. However, current sputtered MoS2 films suffer from inherent defects, including insufficient hardness, poor crystallinity, and susceptibility to oxidation, thereby limiting their longevity and reliability. Here, we present a sandwich-like nanomultilayer architecture comprising alternating MoS2 and tungsten carbide (WC) layers integrated with Ag nanoparticles. This architecture demonstrates robust corrosion resistance, effectively protecting the MoS2 within the film for over 18 months of air exposure and exhibiting minimal corrosion during 21 days of salt spray tests. The remarkable environmental stability of the sandwich-like MoS2/Ag/WC nanomultilayer film is attributed to the creation of numerous heterogeneous interfaces and the spontaneous diffusion and repair of Ag atoms through defect channels of the film, impeding the penetration of corrosive agents. Furthermore, during the frictional process, Ag, characterized by its inherent high mobility and ductility, facilitates the formation of a dense tribofilm on its counterpart ball, encapsulating formed metal oxides to prevent adhesive wear. As a result, the film exhibits a significantly reduced wear rate (1.25 × 10-7 mm3 N-1 m-1) even after long-term salt spray corrosion and air exposure. This study offers a general route for designing MoS2-based materials toward long-lifetime and environmental adaptability via self-repair mechanisms.

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ALPINE (NCT03734016) established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL); here we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n=327) or ibrutinib (n=325). At an overall median follow-up of 42.5 months, progression-free survival benefit with zanubrutinib vs ibrutinib was sustained (HR: 0.68 [95% CI, 0.54-0.84]), including in patients with del(17p)/TP53 mutation (HR: 0.51 [95% CI, 0.33-0.78]) and across multiple sensitivity analyses. Overall response rate remained higher with zanubrutinib compared with ibrutinib (85.6% vs 75.4%); responses deepened over time with complete response/complete response with incomplete bone marrow recovery rates of 11.6% (zanubrutinib) and 7.7% (ibrutinib). While median overall survival has not been reached in either treatment group, fewer zanubrutinib patients have died than ibrutinib patients (HR: 0.77 [95% CI, 0.55-1.06]). With median exposure time of 41.2 and 37.8 months in zanubrutinib and ibrutinib arms, respectively, the most common non-hematologic adverse events included COVID-19-related infection (46.0% vs 33.3%), diarrhea (18.8% vs 25.6%), upper respiratory tract infection (29.3% vs 19.8%), and hypertension (27.2% vs 25.3%). Cardiac events were lower with zanubrutinib (25.9% vs 35.5%) despite similar rates of hypertension. Incidence of atrial fibrillation/flutter was lower with zanubrutinib vs ibrutinib (7.1% vs 17.0%); no cardiac deaths were reported with zanubrutinib vs six cardiac deaths with ibrutinib. This analysis, at 42.5 months median follow-up, demonstrates that zanubrutinib remains more efficacious than ibrutinib with an improved overall safety/tolerability profile.

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Arsenic (As) is a widespread global pollutant, and there is significant controversy surrounding its complex relationship with obesity, primarily focused on short-term exposure. Recognizing the prolonged nature of dietary arsenic exposure, this study involved feeding mice with arsenic-contained food for 14 months. The results showed that mice exposed to arsenic developed a non-alcoholic fatty liver condition, characterized by a light-yellow hue on the liver surface and various pathological alterations in the liver cells, including enlarged nuclei, cellular necrosis, inflammatory infiltration, dysfunctional mitochondria, and endoplasmic reticulum disorganization. There were also disruptions in biochemistry indices, with a significant increase in total cholesterol (TC) level and a decrease in high-density lipoprotein (HDL) level. However, some contradictory observations occurred, such as a significant decrease in body weight, triglyceride (TG) level, and the numbers of lipid droplets. Several genes related to lipid metabolism were tested, and a model was used to explain these discrepancies. Besides, examinations of the colon revealed compromised intestinal barrier function and signs of inflammation. Fecal 16S rRNA sequencing and pseudo-targeted metabolomics revealed disruptions in internal homeostasis, such as modules, nodes, connections, and lipid-related KEGG pathways. Fecal targeted metabolomics analyses of short-chain fatty acids (SCFAs) and bile acids (BAs) demonstrated a significant upregulation in three primary bile acids (CA, CDCA, TCDCA), four secondary bile acids (TUDCA, DCA, LCA, GUDCA), and total SCFAs level. Oxidative stress and inflammation were also evident. Additionally, based on correlation analysis and mediation analysis, it was assumed that changes in the microbiota (e.g., Dubosiella) can impact the liver metabolites (e.g., TGs) through alterations in fecal metabolites (e.g., LPCs). These findings provide a theoretical reference for the long-term effect of arsenic exposure on liver lipid metabolism.

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The transition from simple to complex multicellularity represents a major evolutionary step that occurred in only a few eukaryotic lineages. Comparative analyses of these lineages provide insights into the molecular and cellular mechanisms driving this transition, but limited understanding of the biology of some complex multicellular lineages, such as brown algae, has hampered progress. This Review explores how recent advances in genetic and genomic technologies now allow detailed investigations into the molecular bases of brown algae development. We highlight how forward genetic techniques have identified mutants that enhance our understanding of pattern formation and sexual differentiation in these organisms. Additionally, the existence and nature of morphogens in brown algae and the potential influence of the microbiome in key developmental processes are examined. Outstanding questions, such as the identity of master regulators, the definition and characterization of cell types, and the molecular bases of developmental plasticity are discussed, with insights into how recent technical advances could provide answers. Overall, this Review highlights how brown algae are emerging as alternative model organisms, contributing to our understanding of the evolution of multicellular life and the diversity of body plans.

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Clathrin-mediated endocytosis is an essential cellular pathway that enables signaling and recycling of transmembrane proteins and lipids. During endocytosis, dozens of cytosolic proteins come together at the plasma membrane, assembling into a highly interconnected network that drives endocytic vesicle biogenesis. Recently, multiple groups have reported that early endocytic proteins form flexible condensates, which provide a platform for efficient assembly of endocytic vesicles. Given the importance of this network in the dynamics of endocytosis, how might cells regulate its stability? Many receptors and endocytic proteins are ubiquitylated, while early endocytic proteins such as Eps15 contain ubiquitin-interacting motifs. Therefore, we examined the influence of ubiquitin on the stability of the early endocytic protein network. In vitro, we found that recruitment of small amounts of polyubiquitin dramatically increased the stability of Eps15 condensates, suggesting that ubiquitylation could nucleate endocytic assemblies. In live-cell imaging experiments, a version of Eps15 that lacked the ubiquitin-interacting motif failed to rescue defects in endocytic initiation created by Eps15 knockout. Furthermore, fusion of Eps15 to a deubiquitylase enzyme destabilized nascent endocytic sites within minutes. In both in vitro and live-cell settings, dynamic exchange of Eps15 proteins, a measure of protein network stability, was decreased by Eps15-ubiquitin interactions and increased by loss of ubiquitin. These results collectively suggest that ubiquitylation drives assembly of the flexible protein network responsible for catalyzing endocytic events. More broadly, this work illustrates a biophysical mechanism by which ubiquitylated transmembrane proteins at the plasma membrane could regulate the efficiency of endocytic internalization.

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BACKGROUND: Myelocytomatosis (MYC) transcription factors are crucial mediators of the response of plants to environmental stresses through via binding to DNA regulatory regions. However, few systematic characterizations of MYC genes are available in Cucurbitaceae species. RESULTS: In this study, we identified 10, 8, 12, and 10 MYC genes in Cucumis sativus, Cucumis melo, Citrullus lanatus, and Benincasa hispida, respectively. Characterization revealed that all of the MYC proteins contain a highly conserved H4-V5-E6-E8-R9-R11-R12 sequence, which is essential for the binding of DNA regulatory regions. Evolutionary analysis enabled us to categorize 40 predicted MYC proteins from seven species into five distinct groups and revealed that the expansion of the MYC genes occurred before the divergence of monocots and dicots. The upstream promoter regions of the MYC genes contain a variety of developmental, stress, and hormone-responsive regulatory elements. The expression of cucumber MYC genes varies significantly across organs, with particularly high expression of CsaV3_3G001710 observed across all organs. Transcriptomic analysis revealed that certain cucumber MYC genes undergo specific upregulation or downregulation in response to both biotic and abiotic stressors. In particular, under temperature stress, the cucumber genes CsaV3_3G007980 and CsaV3_3G001710 were significantly upregulated. Interestingly, the homologs of these two genes in C. lanatus presented a similar expression pattern to that in C. sativus, whereas in B. hispida, they presented the opposite pattern, i.e., significant downregulation. These findings indicated that these two genes indeed respond to temperature stress but with different expression patterns, highlighting the divergent functions of homologous genes across different species. CONCLUSIONS: This study analyzed the size and composition of the MYC gene family in four Cucurbitaceae species and investigated stress-responsive expression profiles, especially under temperature stress. All the results showed that MYC genes play important roles in development and stress responses, laying a theoretical foundation for further investigations of these response mechanisms.

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OBJECTIVES: Compared with long-term renal replacement therapy, kidney transplantation is the ideal treatment for end-stage renal disease (ESRD), significantly extending patient life and improving quality of life. Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens, but their medication adherence is generally poor compared with other organ transplant recipients. Medication adherence is closely related to medication literacy and psychological status, yet related studies are limited. This study aims to investigate the current status of medication adherence, inner strength, and medication literacy in kidney transplant patients, analyze the relationships among these 3 factors, and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence. METHODS: A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province. The inner strength, medication literacy, and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale (ISS), the Chinese version of the Medication Literacy Assessment in Spanish and English (MedLitRxSE), and the Chinese version of the Morisky Medication Adherence Scale-8 (C-MMAS-8), respectively. Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence. Correlation analysis was conducted to explore the relationships among medication literacy, medication adherence, and inner strength. Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression, and the mediating effect of inner strength was explored. RESULTS: Among the 421 questionnaires collected, 408 were valid, with an effective rate of 96.91%. The scores of C-MMAS-8, MedLitRxSE, and ISS were 6.64±1.16, 100.63±14.67, and 8.47±4.03, respectively. Among the 408 patients, only 86 (21.08%) patients had a high level of medication adherence, whereas 230 (56.37%) patients had a medium level of medication adherence, and 92 (22.55%) patients had poor medication adherence. Univariate analysis indicated that the kidney transplant patients' age, marital status, education levels, years since their kidney transplant operation, number of hospitalizations after the kidney transplant, and adverse drug reactions showed significant differences in medication adherence (all P<0.05). Correlation analysis showed that inner strength positively correlated with both medication literacy (r=0.183, P<0.001) and medication adherence (r=0.201, P<0.001). Additionally, there was a positive correlation between medication adherence and medication literacy (r=0.236, P<0.001). Inner strength accounted for 13.22% of the total effect in the mediating role between medication literacy and medication adherence. CONCLUSIONS: The level of medication adherence among kidney transplant patients needs improvement, and targeted intervention measures are essential. Inner strength mediates the relationship between medication literacy and medication adherence in these patients. Healthcare professionals should focus on enhancing medication literacy and supporting patients' inner strength to improve medication adherence.

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Normal and damaged microorganisms are related to food safety. The colony-forming unit (CFU) assay and viability of microorganisms have broad applications in food. Traditionally, the CFU assay has been the benchmark for assessing microbial viability across various fields. However, the normal and damaged microorganisms cannot be distinguished. Here, we introduce an improved technology for foods that uses a visible absorbance microplate reader platform for high-throughput quantitative analysis of microbial lag time, doubling time, and CFU. This platform utilizes a 96-well plate and a microplate reader to accurately determine the viable cell number from a five-microliter sample. It boasts the capability to measure a dynamic range spanning from five to seven orders of magnitude, significantly reducing the time required by over 20-fold in comparison to traditional spread plate methods. Additionally, it demonstrates a remarkable ability to detect a single cell within a well. A mild temperature treatment for cell viability detection was implemented and was able to reflect the real microbial quality. Consequently, the high-throughput method as an improved technology provides essential technical support for microbial detection.

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How the brain mentally sorts a series of items in a specific order within working memory (WM) remains largely unknown. We investigated mental sorting using high-throughput electrophysiological recordings in the frontal cortex of macaque monkeys, who memorized and sorted spatial sequences in forward or backward orders according to visual cues. We discovered that items at each ordinal rank in WM were encoded in separate rank-WM subspaces and then, depending on cues, were maintained or reordered between the subspaces, accompanied by two extra temporary subspaces in two operation steps. Furthermore, the cue activity served as an indexical signal to trigger sorting processes. Thus, we propose a complete conceptual framework, where the neural landscape transitions in frontal neural states underlie the symbolic system for mental programming of sequence WM.

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Gelatin methacryloyl (GelMA) holds significant potential in tissue engineering; however, its clinical applications are often constrained by its lack of functional groups. To overcome this limitation, recombinant proteins with multiple biofunctional domains present a promising strategy for GelMA functionalization, enhancing its biological properties. In this study, we developed a rationally designed recombinant collagen-like protein (RC) engineered with multiple biofunctional domains, which demonstrated the ability to upregulate collagen 1α (COL-1α) expression in NIH-3 T3 cells. By utilizing EDC/NHS chemistry, the purified RC was conjugated to GelMA, resulting in GelMA-RC hydrogels that significantly improved cell viability and migration compared to unmodified GelMA. Subsequent in vivo studies showed that RC-modified GelMA exhibited superior wound healing efficacy, largely attributed to enhanced expression of cytokeratin-14 (CK-14) and COL-1α. These findings underscore the potential of RC-functionalized GelMA in promoting diabetic wound repair and suggest broader applicability for functionalizing other biomaterials.

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Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In this study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissue and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and to evaluate its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and repopulation were primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Furthermore, the expression of complement-related genes, such as C4b and Cd47, was substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis and provides new insights into its potential role in SAE.

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Mobile genetic elements (MGEs) enable bacteria to acquire novel genes and traits. However, the functions of cargo genes within MGEs remain poorly understood. The cadmium resistance operon cadDX is present in many gram-positive bacteria. Although cadDX has been reported to be involved in metal detoxification, its regulatory mechanisms and functions in bacterial pathogenesis are poorly understood. This study revealed that cadDX contributes to cadmium resistance, oxidative stress resistance, and virulence in Streptococcus suis, an important zoonotic pathogen in pigs and humans. CadX represses cadD expression by binding to the cadDX promoter. Notably, cadX responds to H2O2 stress through an additional promoter within the cadDX operon, mitigating the harmful effect of excessive cadD expression during oxidative stress. cadDX resides within an 11 K integrative and mobilizable element that can autonomously form circular structures. Moreover, cadDX is found in diverse MGEs, accounting for its widespread distribution across various bacteria, especially among pathogenic streptococci. Transferring cadDX into another zoonotic pathogen, Streptococcus agalactiae, results in similar phenotypes, including resistance to cadmium and oxidative stresses and increased virulence of S. agalactiae in mice. The new functions and regulatory mechanisms of cadDX shed light on the importance of the cadDX system in driving evolutionary adaptations and survival strategies across diverse gram-positive bacteria.

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Diabetic kidney disease (DKD) is one of the common microvascular complications of diabetes, and there are still lack of effective treatments. Huaiqihuang (HQH) is a kind of traditional Chinese medicine mixed preparation, which is mainly made of Trametes robiniophila Murr, Fructus Lycii, and Polygonatum sibiricumhas. It has been shown to be effective in the treatment of DKD, but the specific mechanism has not been fully elucidated. Our results showed that HQH increased the protein expressions of synaptopodin, podocin, WT-1, and Bcl-2, decreased the protein expressions of Bax and cleaved-casepase-3, and activated the NF-ĸB and PI3K/AKT/mTOR pathway in MPC5 cells exposed to high-glucose (HG). Real-time PCR results showed that HQH reduced the mRNA expression of TNF-α, IL-1ß, MCP-1, and IL-6. In conclusion, our results showed that HQH may attenuate podocyte injury by inhibiting MPC5 cell apoptosis induced by HG and NF-κB-mediated inflammation response through activation of the PI3K/AKT/mTOR pathway.

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OBJECTIVES: To evaluate the performance of ultrasound-based deep learning (DL) models in distinguishing breast phyllodes tumors (PTs) from fibroadenomas (FAs) and their clinical utility in assisting radiologists with varying diagnostic experiences. METHODS: We retrospectively collected 1180 ultrasound images from 539 patients (247 PTs and 292 FAs). Five DL network models with different structures were trained and validated using nodule regions annotated by radiologists on breast ultrasound images. DL models were trained using the methods of transfer learning and 3-fold cross-validation. The model demonstrated the best evaluation index in the 3-fold cross-validation was selected for comparison with radiologists' diagnostic decisions. Two-round reader studies were conducted to investigate the value of DL model in assisting six radiologists with different levels of experience. RESULTS: Upon testing, Xception model demonstrated the best diagnostic performance (AUC: 0.87, 95%CI: 0.81-0.92), outperforming all radiologists (all p < 0.05). Additionally, the DL model enhanced the diagnostic performance of radiologists. Accuracy demonstrated improvements of 4%, 4%, and 3% for senior, intermediate, and junior radiologists, respectively. CONCLUSIONS: The DL models showed superior predictive abilities compared to experienced radiologists in distinguishing breast PTs from FAs. Utilizing the model led to improved efficiency and diagnostic performance for radiologists with different levels of experience (6-25 years of work). ADVANCES IN KNOWLEDGE: We developed and validated a DL model based on the largest available dataset to assist in diagnosing PTs. This model has the potential to allow radiologists to discriminate two types of breast tumors which are challenging to identify with precision and accuracy, and subsequently to make more informed decisions about surgical plans.

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Introduction: Diabetic nephropathy (DN) presents a significant therapeutic challenge, compounded by complex pathophysiological mechanisms. Recent studies suggest Exendin-4 (Ex-4) as a potential ameliorative agent for DN, albeit with unclear mechanisms. This research investigates the effects and underlying mechanisms of Ex-4-enriched exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) on DN, focusing on their renoprotective properties and interactions with gut microbiota. Method: Exosomes from hUCMSCs (hUCMSCs-Exo) were loaded with Ex-4 via electroporation. A streptozotocin (STZ) -induced DN mouse model was employed to assess the therapeutic impact of these engineered exosomes. The study further explored immune cell dynamics, mainly CD4+ regulatory T (Treg) cells, using bioinformatics, flow cytometry, and the influence of gut microbiota through antibiotic treatment and specific bacterial reintroduction. Results: Treatment with hUCMSCs-Exo@Ex-4 significantly improved key DN markers, including blood glucose and proteinuria, alleviating kidney damage. A notable decrease in natural Treg cell infiltration in DN was observed, while Ex-4-loaded exosomes promoted CD4+ Treg cell induction. The therapeutic benefits of hUCMSCs-Exo@Ex-4 were diminished upon CD4+ Treg cell depletion, underscoring their role in this context. Notably, CD4+ Treg cell induction correlated with the presence of Prevotella species, and disruption of gut microbiota adversely affected these cells and the therapeutic efficacy of the treatment. However, the reintroduction of Prevotella strains counteracted these adverse effects. Discussion: This study elucidates a novel therapeutic mechanism of Ex-4-loaded hUCMSCs exosomes in DN, highlighting the induction of CD4+ Treg cells mediated by specific gut microbiota components. These findings underscore the potential of leveraging gut microbiota and immune cell interplay in developing effective DN treatments.

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Inflammatory bowel diseases (IBD) significantly contribute to high mortality globally and negatively affect patients' qualifications of life. The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations. Moreover, certain natural or synthetic anti-inflammatory drugs are associated with poor targeting, low drug accumulation at the lesion site, and other side effects, hindering them from exerting their therapeutic effects. Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment. This review mainly discusses the treatment status of IBD, obstacles to drug delivery, design strategies of colon-targeted delivery systems, and perspectives on the existing complementary therapies. Moreover, based on recent reports, we summarized the therapeutic mechanism of colon-targeted drug delivery. Finally, we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.