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INTRODUCTION: This study clarified the expression changes and clinical significance of CD44+CD62L- Treg and CD44-CD62L+ Treg subsets in the peripheral blood of patients with allergic rhinitis (AR). METHODS: The peripheral blood of 39 patients with AR and 42 healthy controls was collected. Clinical data, such as sex, age, IgE titer, allergen screening information and visual analogue scale (VAS) score, were recorded. Changes in serum IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected using the cytometric bead array method. Flow cytometry was used to detect the proportions of Th1, Th2, Th17, TFH, and Th9 cells and the proportions of CD44+CD62L- Treg and CD44-CD62L+ Treg subsets. Correlation analysis was performed between the CD44+CD62L- Treg subsets and the CD44-CD62L+ Treg subsets with clinical indicators (VAS score, total IgE titer), cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ), and Th1/Th2/Th17/TFH/Th9 cell proportions. RESULTS: Compared to the control group, the proportion of total Treg cells and CD44+CD62L- Treg cells in the AR group decreased, and the proportion of CD44-CD62L+ Treg cells increased (p < 0.05). The proportions of CD44+CD62L- Treg cells significantly negatively correlated with Th2 cells (R = -0.5270, p < 0.05) and positively correlated with Treg cytokine IL-10 (R = 0.6447, p < 0.05). In addition, CD44+CD62L- Treg cells negatively correlated with the VAS score (R = -0.4956, p < 0.05), total IgE level (R = -0.4177, p < 0.05) and Th2 cytokine IL-6 level (R = -0.3034, p < 0.05) but positively correlated with the Th1 cytokine IL-2 (R = 0.4331, p < 0.05). In contrast, the proportion of CD44+CD62L- Treg cells significantly positively correlated with the Th2 cells (R = 0.6187, p < 0.05). Moreover, the proportion of CD44-CD62L+ Treg cells positively correlated with the VAS score (R = 0.4060, p < 0.05), total IgE level (R = 0.5224, p < 0.05) and Th2 cytokine IL-4 (R = 0.2647, p < 0.05) and IL-6 levels (R = 0.3824, p < 0.05) but negatively correlated with Th1 cytokine IL-2 (R = -0.3451, p < 0.05) and IL-10 (R = -0.3277, p < 0.05). CONCLUSION: A greater proportion of CD44+CD62L- Tregs correlated with better reversal of the Th1/Th2 imbalance and milder clinical symptoms in AR patients. The presence of more CD44-CD62L+ Tregs correlated with a weaker immunosuppressive effect on Th2 cells and more severe clinical symptoms in AR patients. These findings provide new perspectives for the treatment and disease monitoring of AR.

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The construction of heterojunction is an effective and conventional method to improve the photocatalytic activity of photocatalysts. On this basis, how to further regulate the separation and migration of photogenerated carrier is worthy of further investigation. As a mature and efficient modification method, oxygen defect engineering was used to regulate the S-scheme heterojunction composed of AgIO3 and Bi4Ti3O12 to further enhance the photocatalytic activity of the constructed heterojunction in this study. In addition to improving the visible light absorption of the photocatalyst and providing active sites, the introduction of oxygen vacancies can also strengthen the internal electric field between the two semiconductors by expanding the Fermi level gap, which can be verified by Mott-Schottky experiment and DFT calculations, resulting in more efficient photogenerated carrier separation efficiency. As a result, compared with AgIO3/Bi4Ti3O12, the AgIO3/Bi4Ti3O12 heterojunction modulated by oxygen defect engineering exhibited excellent photocatalytic activity, which proves the feasibility of the regulation of the interfacial electric field. This work provides a new idea for the modulation strategy of the interface electric field.

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BACKGROUND: ChatGPT (OpenAI) has shown great potential in clinical diagnosis and could become an excellent auxiliary tool in clinical practice. This study investigates and evaluates ChatGPT in diagnostic capabilities by comparing the performance of GPT-3.5 and GPT-4.0 across model iterations. OBJECTIVE: This study aims to evaluate the precise diagnostic ability of GPT-3.5 and GPT-4.0 for colon cancer and its potential as an auxiliary diagnostic tool for surgeons and compare the diagnostic accuracy rates between GTP-3.5 and GPT-4.0. We precisely assess the accuracy of primary and secondary diagnoses and analyze the causes of misdiagnoses in GPT-3.5 and GPT-4.0 according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. METHODS: We retrieved 316 case reports for intestinal cancer from the Chinese Medical Association Publishing House database, of which 286 cases were deemed valid after data cleansing. The cases were translated from Mandarin to English and then input into GPT-3.5 and GPT-4.0 using a simple, direct prompt to elicit primary and secondary diagnoses. We conducted a comparative study to evaluate the diagnostic accuracy of GPT-4.0 and GPT-3.5. Three senior surgeons from the General Surgery Department, specializing in Colorectal Surgery, assessed the diagnostic information at the Chinese PLA (People's Liberation Army) General Hospital. The accuracy of primary and secondary diagnoses was scored based on predefined criteria. Additionally, we analyzed and compared the causes of misdiagnoses in both models according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. RESULTS: Out of 286 cases, GPT-4.0 and GPT-3.5 both demonstrated high diagnostic accuracy for primary diagnoses, but the accuracy rates of GPT-4.0 were significantly higher than GPT-3.5 (mean 0.972, SD 0.137 vs mean 0.855, SD 0.335; t285=5.753; P<.001). For secondary diagnoses, the accuracy rates of GPT-4.0 were also significantly higher than GPT-3.5 (mean 0.908, SD 0.159 vs mean 0.617, SD 0.349; t285=-7.727; P<.001). GPT-3.5 showed limitations in processing patient history, symptom presentation, laboratory tests, and imaging data. While GPT-4.0 improved upon GPT-3.5, it still has limitations in identifying symptoms and laboratory test data. For both primary and secondary diagnoses, there was no significant difference in accuracy related to age, gender, or system group between GPT-4.0 and GPT-3.5. CONCLUSIONS: This study demonstrates that ChatGPT, particularly GPT-4.0, possesses significant diagnostic potential, with GPT-4.0 exhibiting higher accuracy than GPT-3.5. However, GPT-4.0 still has limitations, particularly in recognizing patient symptoms and laboratory data, indicating a need for more research in real-world clinical settings to enhance its diagnostic capabilities.

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Objective: To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor (EGFR) 21L858R mutant non-small cell lung cancer (NSCLC) patients in China and to explore the factors influencing the efficacy and safety. Methods: A longitudinal, consecutive case-series, multicenter study with mixed prospective and retrospective data was conducted. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included duration of treatment (DOT), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included. The median follow-up time for these patients was 20.4 months. Among 134 patients with evaluable lesions, the ORR was 70.9% and the DCR was 96.3%. The median PFS was 16.3 [95% confidence interval (95% CI), 13.7-18.9] months. Multivariate Cox regression analysis suggested that the baseline brain metastasis (BM) status [with vs. without BM: hazard ratio (HR), 1.331; 95% CI, 0.720-2.458; P=0.361] and initial doses (45 mg vs. 30 mg: HR, 0.837; 95% CI, 0.427-1.641; P=0.604) did not significantly affect the median PFS. The median DOT was 21.0 (95% CI, 17.5-24.6) months and the median OS was not reached. Genetic tests were performed in 64 patients after progression, among whom 29 (45.3%) patients developed the EGFR 20T790M mutation. In addition, among the 46 patients who discontinued dacomitinib treatment after progression, 31 (67.4%) patients received subsequent third-generation EGFR-tyrosine kinase inhibitors. The most common grade 3-4 adverse events were rash (10.4%), diarrhea (9.1%), stomatitis (7.1%) and paronychia (4.5%). The incidence of grade 3-4 rash was significantly higher in the 45 mg group than that in the 30 mg group (21.9% vs. 7.5%, P=0.042). Conclusions: First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

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Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases.

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The T cell immunoglobulin and ITAM domain (TIGIT) is a recently discovered synergistic co-suppressor molecule that plays an important role in immune response and tumor immune escape in the context of cancer. Importantly, CD155 acts as a receptor for TIGIT, and CD155 signaling to immune cells is mediated through interactions with the co-stimulatory immune receptor CD226 (DNAM-1) and the inhibitory checkpoint receptors TIGIT and CD96. Aspirin (ASA) has been shown to reduce the growth and survival of colorectal cancer (CRC) cells, but the immunological mechanisms involved have not been sufficiently elucidated. In the present study the effects of aspirin on CRC in mice and on Jurkat cells were investigated. Aspirin may suppress the expression of TIGIT on T cells and Regulatory T cells (Tregs) and inhibit T cell viability, and therefore induce tumor cell apoptosis. TIGIT is expressed at higher levels on infiltrating lymphocytes within CRC tumor tissue than adjacent. Further, aspirin could inhibit Jurkat cell proliferation and induce apoptosis via downregulation of TIGIT expression and the anti-apoptosis B cell lymphoma 2 (BCL2) protein and upregulation of BCL2-associated X protein (BAX) expression. The present study suggests that aspirin can inhibit specific aspects of T cell function by reducing interleukin-10 and transforming growth factor-ß1 secretion via the TIGIT-BCL2-BAX signaling pathway, resulting in improved effector T cell function that inhibits tumor progression.

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The ability of Deinococcus bacteria to survive in harsh environments, such as high radiation, extreme temperature, and dryness, is mainly attributed to the generation of unique pigments, especially carotenoids. Although the limited number of natural pigments produced by these bacteria restricts their industrial potential, metabolic engineering and synthetic biology can significantly increase pigment yield and expand their application prospects. In this study, we review the properties, biosynthetic pathways, and functions of key enzymes and genes related to these pigments and explore strategies for improving pigment production through gene editing and optimization of culture conditions. Additionally, studies have highlighted the unique role of these pigments in antioxidant activity and radiation resistance, particularly emphasizing the critical functions of deinoxanthin in D. radiodurans. In the future, Deinococcus bacterial pigments will have broad application prospects in the food industry, drug production, and space exploration, where they can serve as radiation indicators and natural antioxidants to protect astronauts' health during long-term space flights.

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Heavy metals can negatively affect children's neurodevelopment, yet the relationship between heavy metals exposure and attention deficit hyperactivity disorder (ADHD) in children remains unclear. We aimed to examine associations between exposure to five common heavy metals (lead, arsenic, mercury, cadmium, and manganese) with neurodevelopmental toxicity and the risk of ADHD in children. Online databases of PubMed, Web of Science, and Embase were searched before February 29, 2024. A total of 31 studies involving 25,258 children were included in the final analysis. Our findings revealed that lead exposure was positively associated with ADHD risk in children (OR = 1.95, 95% CI: 1.57-2.41) overall, while the associations varied among different WHO regions, with the strongest in the Americas. Sensitivity analyses revealed significant associations between arsenic (OR = 1.53, 95% CI: 1.01-2.32) and manganese (OR = 1.79, 95% CI: 1.28-2.49) exposure and ADHD risk after omitting one study. Arsenic exposure was positively associated with ADHD risk in studies conducted in the Americas and adjusted for environmental smoke exposure. Positive associations between manganese exposure and ADHD risk were also found in several subgroup analyses. No significant associations were found for mercury and cadmium exposure. Dose-response meta-analysis suggested that children with higher blood lead levels exhibited a higher probability of ADHD diagnosis. Lead exposure consistently increases the risk of ADHD in children, while arsenic and manganese exposure may be associated with ADHD under different occasions. More research is required to understand heavy metals' impact on ADHD across varying exposure levels, particularly in less contaminated regions.

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Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence globally. Senescence is characterized by a specific chronic, low-grade, "sterile" inflammatory state known as inflammaging, suggesting that senescence may exacerbate the severity of UC. However, the link between UC and senescence remains unclear. Valnemulin (VAL) is a semi-synthetic derivative of a naturally occurring diterpenoid antibiotic (pleuromutilin), which can inhibit peptidyl transferase. Studies investigating the potential of valnemulin to inhibit senescence and alleviate colitis are currently limited. In this study, we revealed that dextran sulfate sodium (DSS), an inducer of UC, induces senescence in both colon epithelial NCM460 cells and colon tissues. Additionally, VAL, identified from a compound library, exhibited robust anti-senescence activity in DSS-treated NCM460 cells. Identified in our study as an anti-senescence agent, VAL effectively mitigated DSS-induced UC and colonic senescence in mice. Through network pharmacology analysis and experimental validation, the potential signaling pathway (AMPK/NF-κB) for VAL in treating UC was identified. We discovered that DSS significantly inhibited the AMPK signaling pathway and activated the NF-κB signaling pathway. However, supplementation with VAL remarkably restored AMPK activity and inhibited the NF-κB signaling pathway, which led to the inhibition of senescence. In summary, our study demonstrated that DSS-induced UC stimulates the senescence of colonic tissues, and VAL can effectively alleviate DSS-induced colonic damage and reduce colonic senescence. Our research findings provide a new perspective for targeting anti-senescence in the treatment of UC.

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BACKGROUND: Childhood trauma (CT) and family functioning exert significant influences on the course and long-term outcome of major depressive disorder (MDD) and bipolar disorder (BD) patients. Hence, we examined the intricate relationship between CT, family function, and the severity of depressive episodes in MDD and BD patients. METHODS: 562 patients with depressive episodes (336 MDD and 226 BD) and 204 healthy controls (HCs) were included in this retrospective study. The 17-item Hamilton Depression Rating Scale (HAMD-17), Childhood Trauma Questionnaire (CTQ), and Family Adaptability and Cohesion Evaluation Scale (FACES II-CV) were assessed. Pearson correlation analysis and mediation analysis were performed. RESULTS: CT had both a direct and indirect impact on depression severity in MDD and BD groups. In MDD, family adaptability mediated the impact of all CT subtypes on depression severity (Effect = 0.113, [0.030, 0.208]). In BD, family cohesion played a mediating role between emotional neglect (EN) and HAMD-17 scores (Effect = 0.169, [0.008, 0.344]). Notable differences were observed in onset age, illness duration, episode frequency, family history, and CT subtypes between MDD and BD (P < 0.05). LIMITATIONS: This study has several limitations including recall bias, lack of objective family functioning measures, small sample size, and cross-sectional design. CONCLUSIONS: Family functioning mediated the impact of CT on depressive symptoms severity in MDD and BD patients. MDD patients with a history of CT exhibited reduced family adaptability, while BD patients with a history of EN had weaker familial emotional bonds. Our findings highlighted the importance of family-focused preventive interventions in mitigating the long-term effects of CT.

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Traumatic brain injury (TBI) occurs when external physical forces impact the brain, potentially causing long-term issues such as post-traumatic stress disorders and cognitive and physical dysfunctions. The diverse nature of TBI pathology and treatment has led to a rapid acceleration in research on its biological mechanisms over the past decade. This surge presents challenges in assessing, managing, and predicting outcomes for TBI cases. Despite the development and testing of various therapeutic strategies aimed at mitigating neurological decline after TBI, a definitive cure for these conditions remains elusive. Recently, a growing focus has been on preclinical research investigating acupuncture as a potential treatment method for TBI sequelae. Acupuncture, being a cost-effective non-pharmacological therapy, has demonstrated promise in improving functional outcomes after brain injury. However, the precise mechanisms underlying the anticipated improvements induced by acupuncture remain poorly understood. In this study, we examined current evidence from animal studies regarding acupuncture's efficacy in improving functional outcomes post-TBI. We also proposed potential biological mechanisms, such as glial cells (microglia astrocytes), autophagy, and apoptosis. This information will deepen our understanding of the underlying mechanisms through which acupuncture exerts its most beneficial effects post-TBI, assisting in forming new clinical strategies to maximize benefits for these patients.

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OBJECTIVES: Leukemia cell-derived exosomes (LEXs), carrying leukemia cell-specific antigens, can serve as a source of antigen for dendritic cell (DC) vaccine loading. However, LEX-targeted DC-based vaccines have demonstrated limited antitumor immune effects in clinical trials, attributed to the low immunogenicity of LEXs and the scant levels of costimulatory molecules on DCs. The costimulatory molecules CD80 and CD86, which are crucial to DC function, play a significant role in enhancing immune efficacy. In this study, we explored the anti-leukemia immune response of costimulatory molecule gene-modified LEX-targeted DCs (LEX-8086) in vitro and in animal models. METHODS: DCs were incubated with LEX-8086 to produce LEX-8086-targeted DCs (DCsLEX-8086). ELISA, cytotoxicity assays and flow cytometry utilized to assess the antitumor efficacy of DCsLEX8086 in vitro. Flow cytometry was used to evaluate the immunomodulatory function of DCsLEX8086 in animal models. RESULTS: Our findings indicated that LEX-8086 enhanced the maturation and antigen-presenting ability of DCs. Immunization with DCsLEX8086 significantly activated CD8+ T cells and boosted the CTL response in vitro. More importantly, DCsLEX-8086 effectively suppressed tumor growth and exerted anti-leukemia effects in both prophylactic and therapeutic animal models. Furthermore, DCsLEX-8086 promoted the proportion of CD4+ T cells, CD8+ T cells and M1 macrophages in the tumor environments both prophylactically and therapeutically. Treatment with DCsLEX-8086 showed no significant difference in the levels of M2 macrophages but decreased the proportion of Tregs within the tumor bed during therapeutic experiments. CONCLUSION: The results suggested that DCsLEX-8086 induces a more effective anti-leukemia immunity compared to DCsLEX-null in vivo and in vitro. DCsLEX-8086 might achieve antitumor effects by elevating the numbers of CD4+ T cells, CD8+ T cells, and M1 macrophages in tumors. Our findings indicate that DCsLEX-8086 could be leveraged to develop a new, highly effective vaccine for anti-leukemia immunity.

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BACKGROUND: Monotherapy consisting of radiotherapy or chemotherapy has limited efficacy in pancreatic tumors. This study aims to investigate whether the combination of 125I brachytherapy and gemcitabine (GEM) chemotherapy has a synergistic effect on pancreatic cancer (PC). METHODS: In vitro, PANC-1 cells in the exponential phase were treated with 125I radioactive seeds (6 Gy) and GEM (30 nM). Cell proliferation, apoptosis, and mitochondrial membrane potential were measured using the Cell Counting Kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and flow cytometry, respectively. In vivo, we examined the inhibitory effect of three different treatment regimens on tumor growth in mice when combined with 125I brachytherapy and GEM. Next, we investigated the effects of the optimal scheme among the three on the tumor microenvironment, tumor tissue morphology, tumor cell apoptosis, systemic inflammatory response, and levels of apoptosis-related proteins in the tumor. Changes in the tumor microenvironment and levels of apoptosis-related proteins were measured by Western blot. The extent of damage to tumor tissue morphology was assessed by Hematoxylin and Eosin (HE) staining. Tumor cell apoptosis was measured by TUNEL staining. Changes in inflammation-related factors were determined by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The results of in vitro cell experiments demonstrated that the combination of 125I radioactive seeds (6 Gy) and GEM (30 nM) had a stronger inhibitory effect on PANC-1 cells than either alone (p < 0.05). In vivo, data showed that the GEM (after 3 d) + 125I treatment group had the strongest tumor inhibition effect on PC (p < 0.05). Western blot analysis showed that the combined treatment of 125I brachytherapy and GEM caused changes in the expression of collagen and connexin in the tumor microenvironment, promoted tumor cell apoptosis, upregulated the expression of pro-apoptotic proteins, and helped to restore pancreatic function (p < 0.01). CONCLUSION: Our research results suggest that the strategy of 125I seed implantation surgery in mice after 3 days of GEM treatment has a more pronounced synergistic effect on the treatment of PC.

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The regulation of the cell cycle is essential for maintaining normal cellular function, especially in the development of diseases such as lung cancer. The cell cycle consists of four major phases (G1, S, G2 and M phases), which are characterized by a series of precise molecular events to ensure proper cell proliferation and division. In lung cancer cells, cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells. G2 and S-phase expressed 1 (GTSE1) is a regulatory protein found in the cytoplasm of the cell, which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis. GTSE1 affects cell cycle progression by interacting with cyclin-dependent kinase inhibitor 1A (p21) and maintaining the stability of p21, which in turn inhibits the activity of cyclin-dependent kinase 1/2 (CDK1/2). In addition, GTSE1 is also involved in the regulation of tumor protein 53 (p53) signaling pathway. With the assistance of mouse double minute 2 homolog (MDM2), GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation, thus affecting cell cycle and cell death-related signaling pathways. This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer, as well as its potential mechanisms involved in cell cycle regulation.
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BACKGROUND: The management of Spinal Muscular Atrophy (SMA) requires a multidisciplinary treatment approach, wherein rehabilitation constitutes an integral element. In this study, we examined the effects of rehabilitation among Chinese SMA patients and assessed the real-world efficacy of rehabilitation interventions. METHODS: We conducted a cross-sectional online survey on SMA patients from June 9, 2023, to June 30, 2023, through the Meier Advocacy & Support Center using data from the Center's database and electronic questionnaires. The rehabilitation situation of the participants over the past 14 months were investigated. Logistic binary regression was used to analyze the relationship between Pediatric Quality of Life Inventory(PedsQL™) scores and rehabilitation. RESULT: A total of 186 questionnaires were finally analyzed. Only 29 patients did not rehabilitated in the past 14 months. A significant correlation between age and type of rehabilitation, as well as between age and duration of rehabilitation. Patients receiving no rehabilitation or solely home-based rehabilitation exhibited a higher median age of 8.4 compared to those undergoing standard rehabilitation or a combination of standard and home-based rehabilitation, with a median age of 4.9 (z-score = -4.49, p-value < 0.001). In addition, long-term rehabilitation (OR = 0.314, 95%CI = 0.106-0.927, p = 0.04) were negatively correlated with lower PedsQL™ Neuromuscular Module scores, and PedsQL scores in the long-term rehabilitation group were higher than those in the short-term and no-rehabilitation groups (54.2 ± 15.1 vs. 45.9 ± 14.4 and 42.3 ± 14.3, p = 0.01), with the most significant difference observed in the physical function section (59.0 ± 15.8 vs. 46.8 ± 15.2 and 45.6 ± 15.9, p < 0.01). Mobility and exercise (OR = 0.26, 95%CI = 0.08-0.81, p = 0.02), as well as assistive technology (OR = 0.28, 95%CI = 0.10-0.82, p = 0.02), were independently associated with a lower score in a negative direction. CONCLUSION: The study found that long-term rehabilitation was linked to higher PedsQL scores in SMA patients, highlighting the need for standardized rehabilitation programs to enhance function and quality of life.

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We aimed to investigate the species composition of a small mammal community and the prevalence of Echinococcus spp. in a typical endemic area of the Tibetan Plateau. One pika and five rodent species were identified based on the morphological characteristics of 1278 small mammal specimens collected during 2014-2019. Detection of Echinococcus DNA in tissue samples from small mammal specimens revealed that Ochotona curzoniae (pika, total prevalence: 6.02%, 26/432), Neodon fuscus (5.91%, 38/643), N. leucurus (2.50%, 3/120), and Alexandromys limnophilus (21.74%, 10/46) were infected by both E. multilocularis and E. shiquicus; Cricetulus longicaudatus (16.67%, 1/6) was infected by E. shiquicus; and no infection was detected in N. irene (0/15). Neodon fuscus and O. curzoniae were the two most abundant small mammal species. There was no significant difference in the prevalence of pika and the overall rodent species assemblage (6.26%, 53/846); however, the larger rodent populations suggested that more attention should be paid to their role in the transmission of echinococcosis in the wildlife reservoir, which has long been underestimated. Moreover, although DNA barcoding provides a more efficient method than traditional morphological methods for identifying large numbers of small mammal samples, commonly used barcodes failed to distinguish the three Neodon species in this study. The close genetic relationships between these species suggest the need to develop more powerful molecular taxonomic tools.

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Taxanes are kinds of diterpenoids with important bioactivities, such as paclitaxel (taxol®) is an excellent natural broad-spectrum anticancer drug. Attempts to biosynthesize taxanes have made with limited success, mainly due to the bottleneck of the low efficiency catalytic elements. In this study, we developed an artificial synthetic system to produce taxanes from mevalonate (MVA) by coupling biological and chemical methods, which comprises in vitro multi-enzyme catalytic module, chemical catalytic module and yeast cell catalytic module. Through optimizing in vitro multienzyme catalytic system, the yield of taxadiene was increased to 946.7 mg/L from MVA within 8 h and the productivity was 14.2-fold higher than microbial fermentation. By incorporating palladium catalysis, the conversion rate of Taxa-4(20),11(12)-dien-5α-yl acetate (T5α-AC) reached 48 %, effectively addressing the product promiscuity and the low yield rate of T5αOH. Finally, we optimized the expression of T10ßOH in yeast resulting in the biosynthesis of Taxa-4(20),11(12)-dien-5α-acetoxy-10ß-ol(T5α-AC-10ß-ol) at a production of 15.8 mg/L, which displayed more than 2000-fold higher than that produced by co-culture fermentation strategy. These technologies offered a promising new approach for efficient synthesis of taxanes.

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Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3.

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The members of the classic B7 family regulate the immune microenvironment of several malignant tumors. However, the potential relationship between the B7 family and the breast cancer (BrCa) tumor immune microenvironment has remained elusive. In the present study, we provide a comprehensive explanation of the expression, clinical significance, mutation, and immune cell infiltration of B7 family molecules in BrCa. First, we recruited 10 patients with BrCa surgery from the Wuxi Maternal and Child Health Hospital and performed single-cell RNA sequencing (scRNA-seq) analysis to investigate the distribution of B7 family members in multiple immune cell subsets. We focused on B7-2, B7-H3, and B7-H5 molecules of the B7 family and constructed tumor microarrays by self-recruiting patients to perform multiple immunohistochemical (mIHC) analyses and study tumor expression of B7-2, B7-H3, B7-H5 and CD8+ immune cell infiltration. B7-H5 displayed a strong correlation with CD8+ immune cell infiltration. In summary, B7-H5 provides a new perspective for the identification of immunothermal subtypes of BrCa and could function as a switch to reverse BrCa from an "immunologically cold" state to an "immunologically hot" state.