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Hyperuricemia, a major worldwide burden on public hygiene, is closely connected with dietary habits. However, few studies have evaluated the association of dietary diversity with hyperuricemia. To preliminarily reveal the status of a diversified diet in preventing hyperuricemia based on a neighborhood-based, massive-scale cohort in China, a total of 43,493 participants aged 20-74 years old, with no history of hyperuricemia at baseline, were enrolled in the research from April 2016 to December 2019. The Dietary Diversity Score (DDS) was utilized to evaluate the dietary variety and split the participants into the low-, medium-, and high-DDS groups. Information on participants was connected to regional health information systems that acquired data on hyperuricemia instances up to 28 February 2023. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox proportional hazards models. Restricted cubic splines (RCS) were implemented to analyze dose-response correlation. A total of 1460 individuals with newly diagnosed hyperuricemia were observed over a median follow-up period of 5.59 years. Compared to the low-DDS group, HRs for the medium- and high-DDS groups were 0.87 (95% CI 0.76-0.99) and 0.80 (95% CI 0.70-0.91) in the fully adjusted model, respectively. The risk of hyperuricemia incidence was reduced by 5% for each 1 unit of DDS increase. A linear correlation of DDS with hyperuricemia emerged and further revealed that the intake of 8-10 broad categories of food could decrease the incidence of hyperuricemia. Our results validate the dietary principle of "food diversification" recommended in guidelines. Conclusions should be applied with caution considering the paucity of related evidence in additional nations.

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Diabetes is characterized by decreased beta-cell mass and islet dysfunction. The splicing factor SRSF2 plays a crucial role in cell survival, yet its impact on pancreatic beta cell survival and glucose homeostasis remains unclear. We observed that the deletion of Srsf2 specifically in beta cells led to time-dependent deterioration in glucose tolerance, impaired insulin secretion, decreased islet mass, an increased number of alpha cells, and the onset of diabetes by the age of 10 months in mice. Single-cell RNA sequencing (scRNA-seq) analyses revealed that, despite an increase in populations of unfolded protein response (UPR)-activated and undifferentiated beta cells within the SRSF2_KO group, there was a notable decrease in the expression of UPR-related and endoplasmic reticulum (ER)-related genes, accompanied by a loss of beta-cell identity. This suggests that beta cells have transitioned from an adaptive phase to a maladaptive phase in islets of 10-month-old SRSF2_KO mice. Further results demonstrated that deletion of SRSF2 caused decreased proliferation in beta cells within 3-month-old islets and Min6 cells. These findings underscore the essential role of SRSF2 in controlling beta-cell proliferation and preserving beta-cell function in mice.

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The NSP14 protein of SARS-CoV-2 not only facilitates viral replication but also plays a pivotal role in activating the host immune system by enhancing cytokine production. In this study, we found that NSP14 markedly activated the activator protein 1 (AP-1) pathway by increasing the phosphorylation of ERK (p-ERK), which enters the nucleus and promotes AP-1 transcription. The screening of the main proteins of the ERK pathway revealed that NSP14 could interact with MEK, a kinase of ERK, and increase the level of phosphorylated MEK. The addition of the MEK inhibitor U0126 suppressed the level of p-ERK induced by NSP14 and partly blocked cytokine production, suggesting that NSP14 activates MEK to enhance AP-1 signaling. Further investigation demonstrated that the ExoN domain of NSP14 might be crucial for the interaction and activation of MEK. These results suggest a novel mechanism by which NSP14 of SARS-CoV-2 induces a proinflammatory response in the host.

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SRSF2 plays a dual role, functioning both as a transcriptional regulator and a key player in alternative splicing. The absence of Srsf2 in MyoD + progenitors resulted in perinatal mortality in mice, accompanied by severe skeletal muscle defects. SRSF2 deficiency disrupts the directional migration of MyoD progenitors, causing them to disperse into both muscle and non-muscle regions. Single-cell RNA-sequencing analysis revealed significant alterations in Srsf2-deficient myoblasts, including a reduction in extracellular matrix components, diminished expression of genes involved in ameboid-type cell migration and cytoskeleton organization, mitosis irregularities, and premature differentiation. Notably, one of the targets regulated by Srsf2 is the serine/threonine kinase Aurka. Knockdown of Aurka led to reduced cell proliferation, disrupted cytoskeleton, and impaired differentiation, reflecting the effects seen with Srsf2 knockdown. Crucially, the introduction of exogenous Aurka in Srsf2-knockdown cells markedly alleviated the differentiation defects caused by Srsf2 knockdown. Furthermore, our research unveiled the role of Srsf2 in controlling alternative splicing within genes associated with human skeletal muscle diseases, such as BIN1, DMPK, FHL1, and LDB3. Specifically, the precise knockdown of the Bin1 exon17-containing variant, which is excluded following Srsf2 depletion, profoundly disrupted C2C12 cell differentiation. In summary, our study offers valuable insights into the role of SRSF2 in governing MyoD progenitors to specific muscle regions, thereby controlling their differentiation through the regulation of targeted genes and alternative splicing during skeletal muscle development.

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α-Cobalt(II) (CoII) hydroxide (compound 1) incorporating cyanuric acid layers was synthesized via the solvothermal method. 1 exhibited two distinct characteristics, which were different from reported α-CoII hydroxides. (i) The presence of abundant consecutive hydrogen bonds between the adjacent hydroxide layers enhanced the driving force of crystallization along the direction of the c axis. Thus, 1 revealed high crystallinity without the disorder phenomenon. (ii) 1 showed low symmetry. The configuration of CoTd sites did not follow the regular triangular net. The low symmetry favored the magnetic anisotropy. Thus, 1 revealed ferrimagnetic behavior with a high Néel temperature (TN = 56.8 K) and coercivity (Hc = 36 kOe at 2 K). The ferrimagnetic behavior of 1 was validated via the Hubbard U correction density functional theory.

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Pancreatic cancer is highly lethal with limited effective treatments. This study explores the therapeutic effects of eupalinolide B (EB) from Eupatorium lindleyanum DC on pancreatic cancer cells. Through cellular functional assays, we observed that EB effectively inhibits cell viability, proliferation, migration, and invasion. In a xenograft mouse model, EB treatment resulted in reduced pancreatic cancer tumor growth and decreased expression of Ki-67. Mechanistically, EB induces apoptosis, elevates reactive oxygen species (ROS) levels, and disrupts copper homeostasis. RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) identified copper ion binding pathways and potential involvement in cuproptosis. Furthermore, EB enhances the cytotoxic effects of elesclomol (ES), increasing ROS levels in a copper-dependent manner and exhibiting synergistic cytotoxicity. These findings suggest that EB, either alone or in combination with ES, represents a promising strategy for targeting metal ion dysregulation and inducing potential cuproptosis in pancreatic cancer, offering a potential improvement in therapeutic outcomes.

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Factors that determine nonresponse to immune checkpoint inhibitor (ICI) remain unclear. The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for cancer treatment. There is, however, a lack of CAF-related signature in predicting response to immunotherapy in gastric cancer (GC). Single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data of GC immunotherapy were downloaded from the Gene Expression Omnibus database. Bulk RNA-seq data were obtained from The Cancer Genome Atlas. The R package 'Seurat' was used for scRNA-seq data processing. Cellular infiltration, receptor-ligand interactions, and evolutionary trajectory analysis were further explored. Differentially expressed genes affecting overall survival were obtained using the limma package. Weighted Gene Correlation Network Analysis was used to identify key modules of immunotherapy nonresponder. Prognostic model was constructed by univariate Cox and least absolute contraction and selection operator analysis using the intersection of activated fibroblast genes (AFGs) with key module genes. The differences in clinicopathological features, immune microenvironment, immunotherapy prediction, and sensitivity to small molecule agents between the high- and low-risk groups were further investigated. Based on scRNA-seq, we finally identified 20 AFGs associations with the prognosis of GC patients. AFGs' high expression levels were correlated with both poor prognosis and tumor progression. Three genes (FRZB, SPARC, and FKBP10) were identified as immunotherapy nonresponse-related fibroblast genes and used to construct the prognostic signature. This signature is an independent significant risk factor affecting the clinical outcomes of GC patients. Remarkably, there were more CD4 memory T cells, resting mast cells, and M2 macrophages infiltrating in the high-risk group, which was characterized by higher tumor immune exclusion. Moreover, patients with higher risk scores were more prone to not respond to immunotherapy but were more sensitive to various small molecule agents, such as memantine. In conclusion, this study constructed a fibroblast-associated ICI nonresponse gene signature, which could predict the response to immunotherapy. This study potentially revealed a novel way to overcome immune resistance in GC.

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Monosubstituted tetrazines are important bioorthogonal reactive tools due to their rapid ligation with trans-cyclooctene. However, their application is limited by the reactivity-stability paradox in biological environments. In this study, we demonstrated that steric effects are crucial in resolving this paradox through theoretical methods and developed a simple synthetic route to validate our computational findings, leading to the discovery of 1,3-azole-4-yl and 1,2-azole-3-yl monosubstituted tetrazines as superior bioorthogonal tools. These new tetrazines surpass previous tetrazines in terms of high reactivities and elevated stabilities. The most stable tetrazine exhibits a reasonable stability (71% remaining after 24 h incubation in cell culture medium) and an exceptionally high reactivity (k2 > 104 M-1 s-1 toward trans-cyclooctene). Due to its good stability in biological systems, a noncanonical amino acid containing such a tetrazine side chain was genetically encoded into proteins site-specifically via an expanded genetic code. The encoded protein can be efficiently labeled using cyclopropane-fused trans-cyclooctene dyes in living mammalian cells with an ultrafast reaction rate exceeding 107 M-1 s-1, making it one of the fastest protein labeling reactions reported to date. Additionally, we showed its superiority through in vivo reactions in living mice, achieving an efficient local anchoring of proteins. These tetrazines are expected to be optimal bioorthogonal reactive tools within living systems.

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BACKGROUND: Early detection and treatment of colorectal cancer (CRC) is crucial for improving patient survival rates. This study aims to identify signature molecules associated with CRC, which can serve as valuable indicators for clinical hematological screening. METHOD: We have systematically searched the Human Protein Atlas database and the relevant literature for blood protein-coding genes. The CRC dataset from TCGA was used to compare the acquired genes and identify differentially expressed molecules (DEMs). Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify modules of co-expressed molecules and key molecules within the DEMs. Signature molecules of CRC were then identified from the key molecules using machine learning. These findings were further validated in clinical samples. Finally, Logistic regression was used to create a predictive model that calculated the likelihood of CRC in both healthy individuals and CRC patients. We evaluated the model's sensitivity and specificity using the ROC curve. RESULT: By utilizing the CRC dataset, WGCNA analysis, and machine learning, we successfully identified seven signature molecules associated with CRC from 1478 blood protein-coding genes. These markers include S100A11, INHBA, QSOX2, MET, TGFBI, VEGFA and CD44. Analyzing the CRC dataset showed its potential to effectively discriminate between CRC and normal individuals. The up-regulated expression of these markers suggests the existence of an immune evasion mechanism in CRC patients and is strongly correlated with poor prognosis. CONCLUSION: The combined detection of the seven signature molecules in CRC can significantly enhance diagnostic efficiency and serve as a novel index for hematological screening of CRC.

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Reusable point-of-care biosensors offer a cost-effective solution for serial biomarker monitoring, addressing the critical demand for tumour treatments and recurrence diagnosis. However, their realization has been limited by the contradictory requirements of robust reusability and high sensing capability to multiple interactions among transducer surface, sensing probes and target analytes. Here we propose a drug-mediated organic electrochemical transistor as a robust, reusable epidermal growth factor receptor sensor with striking sensitivity and selectivity. By electrostatically adsorbing protonated gefitinib onto poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and leveraging its strong binding to the epidermal growth factor receptor target, the device operates with a unique refresh-in-sensing mechanism. It not only yields an ultralow limit-of-detection concentration down to 5.74 fg ml-1 for epidermal growth factor receptor but, more importantly, also produces an unprecedented regeneration cycle exceeding 200. We further validate the potential of our devices for easy-to-use biomedical applications by creating an 8 × 12 diagnostic drug-mediated organic electrochemical transistor array with excellent uniformity to clinical blood samples.

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The excited-state property determines the occurrence of photofunctions in organic materials. We have developed a fragment frontier molecular orbital model for the donor-acceptor-type (D-A-type) systems and constructed molecular descriptors of the excited-state property with charge transfer (CT) or local excitation (LE) based on the orbital information on constituent D and A fragments. Applying these descriptors, we rapidly screened 1CT or 1LE and 3CT or 3LE molecules from 2500 molecules generated by the binding of 50 donors and 50 acceptors, and the results of 26 molecules were confirmed by available experiments and first-principles calculations. Moreover, the modulation of these descriptors by chemical groups allows the rational design of target excited states. This work is significant for high-throughput screening of excellent organic photofunctional materials from a giant chemical database.

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The first examples of RE/Si FLPs (RE: rare-earth metal, FLPs: frustrated Lewis pairs), namely Yb/Si FLPs were synthesized, where Yb⋯Si distances are in the range of 3.55 to 3.72 Å. These FLPs react with triphenylphosphine sulfide and aryl isocyanide to produce novel silylyne group transfer products through dissociation of naphthalene.

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Coronary heart disease is a common cardiovascular disease, attacking about 11.4 million patients in China. With increasing prevalence and mortality year by year, coronary heart disease has become a major factor threatening human health and public health. Although primary and secondary prevention, intervention, coronary artery bypass grafting and other interventions have reduced the death rate, there are drug(aspirin) resistance, secondary nitroglycerin failure, post-intervention fatigue, chest tightness, and an-xiety, and complication with a high risk of bleeding, which have become the key clinical and scientific issues needed to be resolved. Coronary heart disease belongs to the category of chest impediment and heart pain in traditional Chinese medicine(TCM). The TCM etiology of this disease includes external contraction of cold, emotional disorders, constitutional insufficiency, physical weakness, and labor injury, which are closely related to sympathetic nerve activity, state of cardiac and psychological diseases, family history, and cardiovascular metabolic disorders in modern medicine. The TCM causes of coronary heart disease include Qi depression, phlegm turbidity, blood stasis, fire-heat, cold congealing, and healthy Qi deficiency, which are associated with emotional factors such as anxiety and depression, abnormal lipid metabolism, abnormalities in blood circulation and coagulation, inflammatory responses, hyperactive immune responses, and heart failure, chronic wasting disease, or aging, respectively. Accordingly, the patients with Qi depression should be treated with Chaihu Longgu Muli Decoction, and those with phlegm turbidity should be treated with Wendan Decoction and Gualou Xiebai Banxia Decoction. Xuefu Zhuyu Decoction and Guizhi Fuling Pills are recommended for blood stasis, Xiaoxianxiong Decoction and Sanhuang Xiexin Decoction for fire-heat, Zhishi Xiebai Guizhi Decoction for cold congealing, and Renshen Decoction for healthy Qi deficiency. Due to the changes in the spectrum of diseases from ancient to modern times as well as the differences in physical constitution, the key cause of coronary heart disease has evolved from the chest Yang deficiency and cold congealing to Qi depression, phlegm turbidity, phlegm combined with stasis, and fire-heat, showing a shift from cold to heat and from deficiency to excess. The combination of classic formulas presents a pattern. That is, the core formula-syndrome correspondence of a disease often fixedly appears with other formula-syndrome correspondence, which may be related to the development of the pathophysiological mechanism of the disease. In the clinical application of modern pharmacological results, the research team has formulated the clinical principle of pathogenesis corresponding to pathological changes and medicinal nature corresponding pharmacological effects. The modern pharmacological research on classic formulas is conducive to targeted treatment. Moreover, classic formulas help to ameliorate aspirin resistance, clopidogrel resistance, post-intervention anxiety, and high risk of bleeding and address the lack of effective blockade of critical lesions in the coronary artery and the progression of post-infarction heart failure. The innovative understanding of the etiology and pathogenesis of co-ronary heart disease helps to improve the clinical efficacy of TCM and the clinical system for treating coronary heart disease with classic formulas.

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Based on the systematic deconstruction of multi-dimensional and multi-target biological networks, modular pharmacology explains the complex mechanism of diseases and the interactions of multi-target drugs. It has made progress in the fields of pathogenesis of disease, biological basis of disease and traditional Chinese medicine(TCM) syndrome, pharmacological mechanism of multi-target herbs, compatibility of formulas, and discovery of new drug of TCM compound. However, the complexity of multi-omics data and biological networks brings challenges to the modular deconstruction and analysis of the drug networks. Here, we constructed the "Computing Platform for Modular Pharmacology" online analysis system, which can implement the function of network construction, module identification, module discriminant analysis, hub-module analysis, intra-module and inter-module relationship analysis, and topological visualization of network based on quantitative expression profiles and protein-protein interaction(PPI) data. This tool provides a powerful tool for the research on complex diseases and multi-target drug mechanisms by means of modular pharmacology. The platform may have broad range of application in disease modular identification and correlation mechanism, interpretation of scientific principles of TCM, analysis of complex mechanisms of TCM and formulas, and discovery of multi-target drugs.

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Objective: The purpose of this study is to analyze the inherent relationship between the score values and the biomechanical characteristics of the forward kicking motion, we aim to identify the fundamental variables influencing the score values of the forward kicking motion and establish the key biomechanical factors that effectively trigger scoring in the forward kicking motion. Methods: The DaeDo electronic scoring system was used with the Vicon optical motion capture system and the Kistler 3D force platform to obtain kinematic and kinetic variables of the front roundhouse kick motion. Linear bivariate correlation analysis and principal component analysis were used to analyze the associations between kinematic, kinetic variables, and scoring values, and summarize key biomechanical factors for effectively scoring. Results: The peak ankle plantar flexion angle and knee extension torque of the kicking leg showed a significant negative correlation with scoring values (r < 0, p < 0.05), while other variables showed no statistical significance. The peak knee flexion angle and hip extension angular velocity of the supporting leg showed a significant positive correlation with scoring values (r > 0, p < 0.01), while the peak ankle plantar flexion torque showed a significant negative correlation with scoring values (r < 0, p < 0.05), and other variables showed no statistically significant correlation. The absolute values of eigenvectors of the first and second principal components, which included hip angular velocity, ankle angle, knee torque, and hip torque, were relatively large, indicating their strong influence on effective scoring triggering. Conclusion: Maintaining ankle dorsiflexion and a larger knee flexion angle in the kicking leg is favorable for triggering scoring. Higher knee flexion angle and hip extension angular velocity in the supporting leg are also advantageous for triggering scoring. "Body posture" and "Strength" are key factors that effectively trigger scoring.

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Glioblastoma (GBM) remains the most lethal primary brain tumor, characterized by dismal survival rates. Novel molecular targets are urgently required to enhance therapeutic outcomes. A combination of bioinformatics analysis and experimental validation was employed to investigate the role of EGFLAM in GBM. The Chinese Glioma Genome Atlas provided a platform for gene expression profiling, while siRNA-mediated knockdown and overexpression assays in GBM cell lines, alongside in vivo tumorigenesis models, facilitated functional validation. EGFLAM was found to be significantly overexpressed in GBM tissues, correlating with adverse prognostic factors and higher tumor grades, particularly in patients over the age of 41. Functional assays indicated that EGFLAM is vital for maintaining GBM cell proliferation, viability, and invasiveness. Knockdown of EGFLAM expression led to a marked decrease in tumorigenic capabilities. Proteomic interactions involving EGFLAM, such as with NUP205, were implicated in cell cycle regulation, providing insight into its oncogenic mechanism. In vivo studies further demonstrated that silencing EGFLAM expression could inhibit tumor growth, underscoring its therapeutic potential. The study identifies EGFLAM as a pivotal oncogenic factor in GBM, serving as both a prognostic biomarker and a viable therapeutic target. These findings lay the groundwork for future research into EGFLAM-targeted therapies, aiming to improve clinical outcomes for GBM patients.

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This study focuses on the clinical features affecting the outcome and prognosis of multiple myeloma (MM) associated with spinal fractures. We retrospectively analyzed the clinical data of 194 MM patients with pathologic thoracic or lumbar spine fractures admitted to Dongying People's Hospital from April 2005 to February 2021. Patients were categorized into effective and ineffective groups based on post-treatment pain scores and mobility to analyze the influencing factors on the efficacy. Univariate analysis showed that age ≥60 years, number of vertebral fractures ≥2, and conservative treatment were associated with the outcomes. The number of vertebral fractures ≥2 (OR=2.198, P=0.034) and conservative treatment (OR=1.685, P=0.012) were identified as independent risk factors. In addition, survival curves were depicted using the Kaplan-Meier method, and independent risk factors affecting 2-year survival included efficacy (HR=17.924, P<0.001), age (HR=3.544, P=0.003) and International Staging System staging (HR=10.770, P=0.001). Finally, we constructed a high-accuracy prognostic model for predicting 2-year survival of MM patients with pathologic fractures (AUC=0.756). In conclusion, this study identified independent risk factors affecting the outcome and survival of MM patients with morbid fractures by systematically analyzing clinical characteristics and constructing a survival prediction model, thus providing effective guideline for clinical treatment.

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Hepatocellular carcinoma (HCC) has high incidence and mortality rates worldwide. Damaged mitochondria are characterized by the overproduction of reactive oxygen species (ROS), which can promote cancer development. The prognostic value of the interplay between mitochondrial function and oxidative stress in HCC requires further investigation. Gene expression data of HCC samples were collected from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC). We screened prognostic oxidative stress mitochondria-related (OSMT) genes at the bulk transcriptome level. Based on multiple machine learning algorithms, we constructed a consensus oxidative stress mitochondria-related signature (OSMTS), which contained 26 genes. In addition, we identified six of these genes as having a suitable prognostic value for OSMTS to reduce the difficulty of clinical application. Univariate and multivariate analyses verified the OSMTS as an independent prognostic factor for overall survival (OS) in HCC patients. The OSMTS-related nomogram demonstrated to be a powerful tool for the clinical diagnosis of HCC. We observed differences in biological function and immune cell infiltration in the tumor microenvironment between the high- and low-risk groups. The highest expression of the OSMTS was detected in hepatocytes at the single-cell transcriptome level. Hepatocytes in the high- and low-risk groups differed significantly in terms of biological function and intercellular communication. Moreover, at the spatial transcriptome level, high expression of OSMTS was mainly in regions enriched in hepatocytes and B cells. Potential drugs targeting specific risk subgroups were identified. Our study revealed that the OSMTS can serve as a promising tool for prognosis prediction and precise intervention in HCC patients.

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Background: Tracheoesophageal fistula (TEF) remains a rare but significant clinical challenge, mainly due to the absence of established, effective treatment approaches. The current focus of therapeutic strategy is mainly on fistula closure. However, this approach often misses important factors, such as accelerating fistula contraction and fostering healing processes, which significantly increases the risk of disease recurrence. Methods: In order to investigate if Mesenchymal Stem Cells (MSCs) can enhance fistula repair, developed a TEF model in beagles. Dynamic changes in fistula diameter were monitored by endoscopy. Concurrently, we created a model of LPS-induced macrophage to replicate the inflammatory milieu typical in TEF. In addition, the effect of MSC supernatant on inflammation mitigation was evaluated. Furthermore, we looked at the role of TLR4/NF-κB pathway plays in the healing process. Results: Our research revealed that the local administration of MSCs significantly accelerated the fistula's healing process. This was demonstrated by a decline in TEF apoptosis and decrease in the production of pro-inflammatory cytokines. Furthermore, in vivo experiments demonstrated that the MSC supernatant was effective in suppressing pro-inflammatory cytokine expression and alleviating apoptosis in LPS-induced macrophages. These therapeutic effects were mainly caused by the suppression of TLR4/NF-κB pathway. Conclusion: According to this study, MSCs can significantly improve TEF recovery. They achieve this via modulating apoptosis and inflammatory responses, mainly by selectively inhibiting the TLR4/NF-κB pathway.

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Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.