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Connective tissue diseases-related pulmonary arterial hypertension (CTD-PAH) is a disease characterized by an elevated pulmonary artery pressure that arises as a complication of connective tissue diseases. The number of patients with CTD-PAH accounts for 25.3% of all PAH patients. The main pathological features of CTD-PAH are thickening of intima, media and adventitia of pulmonary arterioles, increased pulmonary vascular resistance, autoimmune activation and inflammatory reaction. It is worth noting that abnormal immune activation will produce autoantibodies and release cytokines, and abnormal immune cell recruitment will promote inflammatory environment and vascular remodeling. Therefore, almost all forms of connective tissue diseases are related to PAH. In addition to general therapy and targeted drug therapy for PAH, high-dose glucocorticoid combined with immunosuppressant can quickly alleviate and stabilize the basic CTD-PAH disease. Given this, the development of therapeutic approaches targeting immune dysregulation and heightened inflammation is recognized as a promising strategy to prevent or reverse the progression of CTD-PAH. This review explores the potential mechanisms by which immune cells contribute to the development of CTD-PAH and examines the clinical application of immunosuppressive therapies in managing CTD-PAH.

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Doenças do Tecido Conjuntivo , Hipertensão Arterial Pulmonar , Humanos , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/complicações , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/imunologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Animais , Imunossupressores/uso terapêutico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/tratamento farmacológico

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Introduction: The incidence of hemiplegia caused by stroke is high. In particular, lower limb dysfunction affects the daily activities of patients, and lower limb robotic devices have been proposed to provide rehabilitation therapy to improve balance function in this patient population. Objective: To assess the effectiveness of the LiteStepper® unilateral lower limb exoskeleton (ULLE) combined with conventional treatment for balance function training in patients with post-stroke hemiplegia. Methods: This multicenter randomized controlled trial, conducted in the convalescent rehabilitation ward of four hospitals, involved 92 patients in their post-stroke phase. Participants were randomized into an experimental group (EG) or a conventional group (CG). The EG adopted the LiteStepper® ULLE combined with conventional treatment for 21 days. The CG underwent a standard daily rehabilitation routine for 21 days. The Berg Balance Scale (BBS), Functional Ambulation Category scale (FAC), 6-min walk test (6MWT), and Barthel Index (Barthel) were used for evaluations before and after 21 days of rehabilitative training. Results: The BBS scores in EG was significantly elevated compared to CG, exhibiting a profound statistical difference (P< 0.0001). Notably, these disparities persisted at both day 21 (P < 0.0001) and day 14 (P < 0.0047) post-intervention, underscoring the efficacy of the treatment in the EG. The EG demonstrated a markedly greater improvement in BBS scores from pre-rehabilitation to 21 days post-training, significantly outperforming the CG. Furthermore, at both day 14 and day 21, functional assessments including the FAC, 6MWT, and Barthel revealed improvements in both groups. However, the improvements in the EG were statistically significant compared to the CG at both time points: day 14 (FAC, P = 0.0377; 6MWT, P = 0.0494; Barthel, P = 0.0225) and day 21 (FAC, P = 0.0015; 6MWT, P = 0.0005; Barthel, P = 0.0004). These findings highlight the superiority of the intervention in the EG in enhancing functional outcomes. Regarding safety, the analysis revealed a solitary adverse event (AEs) related to the LiteStepper®ULLE device during the study period, affirming the combination therapy's safety profile when administered alongside conventional balance training in post-stroke hemiplegic patients. This underscores the feasibility and potential of incorporating LiteStepper®ULLE into rehabilitation protocols for this patient population. Discussion and significance: The LiteStepper® ULLE combined with conventional treatment is effective and safe for balance function training in patients with post-stroke hemiplegia.

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Colorectal cancer is the third most common cancer and the second most lethal cancer in the world. The main cause of the disease is due to dietary and behavioral factors. The treatment of this complex disease is mainly based on traditional treatments, including surgery, radiotherapy, and chemotherapy. Due to its high prevalence and high morbidity, more effective treatments with fewer side effects are urgently needed. In recent years, immunotherapy has become a potential therapeutic alternative and one of the fastest-developing treatments. Immunotherapy inhibits tumor growth by activating or enhancing the immune system to recognize and attack cancer cells. This review presents the latest immunotherapies for immune checkpoint inhibitors, cell therapy, tumor-infiltrating lymphocytes, and oncolytic viruses. Some of these have shown promising results in clinical trials and are used in clinical treatment.

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Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Imunoterapia , Humanos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Animais , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/imunologia

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BACKGROUND: Infectious disease (ID) models have been the backbone of policy decisions during the COVID-19 pandemic. However, models often overlook variation in disease risk, health burden, and policy impact across social groups. Nonetheless, social determinants are becoming increasingly recognized as fundamental to the success of control strategies overall and to the mitigation of disparities. METHODS: To underscore the importance of considering social heterogeneity in epidemiological modeling, we systematically reviewed ID modeling guidelines to identify reasons and recommendations for incorporating social determinants of health into models in relation to the conceptualization, implementation, and interpretations of models. RESULTS: After identifying 1,372 citations, we found 19 guidelines, of which 14 directly referenced at least 1 social determinant. Age (n = 11), sex and gender (n = 5), and socioeconomic status (n = 5) were the most commonly discussed social determinants. Specific recommendations were identified to consider social determinants to 1) improve the predictive accuracy of models, 2) understand heterogeneity of disease burden and policy impact, 3) contextualize decision making, 4) address inequalities, and 5) assess implementation challenges. CONCLUSION: This study can support modelers and policy makers in taking into account social heterogeneity, to consider the distributional impact of infectious disease outbreaks across social groups as well as to tailor approaches to improve equitable access to prevention, diagnostics, and therapeutics. HIGHLIGHTS: Infectious disease (ID) models often overlook the role of social determinants of health (SDH) in understanding variation in disease risk, health burden, and policy impact across social groups.In this study, we systematically review ID guidelines and identify key areas to consider SDH in relation to the conceptualization, implementation, and interpretations of models.We identify specific recommendations to consider SDH to improve model accuracy, understand heterogeneity, estimate policy impact, address inequalities, and assess implementation challenges.

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High-performance organic cathode interlayers (CILs) play a crucial role in the advance of organic solar cells (OSCs). However, organic CILs have exhibited inferior performances to their inorganic counterparts over a long time, due to the inherent shortcoming of poor charge transporting capability. Here, we designed and synthesized a perylene-diimide (PDI) zwitterion PDI-B as high-performance organic CIL for OSCs. We revealed that an obvious H-aggregate of PDI-B was formed during the solution processing, thereby significantly enhancing the charge transporting capability of the CIL. Compared to the classic PDINN, the π-π stacking distance of PDI-B was reduced from 4.2 Å to 3.9 Å, which further facilitated the charge transport. Consequently, PDI-B showed a high conductivity of 1.81×10-3S/m; this is comparable to that of inorganic CILs. The binary OSC showed an elevated PCE of 19.23%, which is among the highest PCE values for binary OSCs. Benefitting from improved solvent resistance and good compatibility with large-area processing method of PDI-B, the photovoltaic performances of inverted and 1-cm2 OSC were significantly improved. The results from this work provide a new approach of optimizing the condensed structure of PDI film to boost the charge conductivity, opening an avenue to develop high-performance PDI-based CILs.

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Membrane-based reverse electrodialysis is globally recognized as a promising technology for harnessing osmotic energy. However, its practical application is greatly restricted by the poor anti-fouling ability of existing membrane materials. Inspired by the structural and functional models of natural cytochrome c oxidases (CcO), the first use of atomically precise homonuclear diatomic iron composites as high-performance osmotic energy conversion membranes with excellent anti-fouling ability is demonstrated. Through rational tuning of the atomic configuration of the diatomic iron sites, the oxidase-like activity can be precisely tailored, leading to the augmentation of ion throughput and anti-fouling capacity. Composite membranes featuring direct Fe-Fe motif configurations embedded within cellulose nanofibers (CNF/Fe-DACs-P) surpass state-of-the-art CNF-based membranes with power densities of ca. 6.7 W m-2 and a 44.5-fold enhancement in antimicrobial performance. Combined, experimental characterization and density functional theory simulations reveal that homonuclear diatomic iron sites with metal-metal interactions can achieve ideally balanced adsorption and desorption of intermediates, thus realizing superior oxidase-like activity, enhanced ionic flux, and excellent antibacterial activity.

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BACKGROUND: The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC. METHODS: The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8+ T cell isolation experiment, coculture experiment, enzyme-linked immunosorbent assay (ELISA), and flow cytometric analysis were employed to elucidate the underlying mechanism through which MED1 operates in the progression of OSCC. RESULTS: MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8+ T cells in the tumor microenvironment. CONCLUSIONS: Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8+ T cell antitumor immunity, suggesting that MED1 may serve as a novel prognostic marker and therapeutic target in OSCC.

Assuntos

Linfócitos T CD8-Positivos , Carcinoma de Células Escamosas , Progressão da Doença , Metaloproteinase 9 da Matriz , Subunidade 1 do Complexo Mediador , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Animais , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Subunidade 1 do Complexo Mediador/metabolismo , Subunidade 1 do Complexo Mediador/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Prognóstico

RESUMO

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection caused by the yeast-like fungus P. jirovecii. As recommended by some guidelines, the first-line treatment for this infection is trimethoprim-sulfamethoxazole (TMP-SMX), and the second-line treatment includes drugs such as dapsone, pentamidine, primaquine, Atovaquone, clindamycin, and caspofungin. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked gene disorder in which treatment with oxidizing drugs, such as sulfonamides, dapsone, primaquine, can directly destroy hemoglobin present in red blood cells (RBCs), thereby inducing methemoglobin and hemolysis. Case presentation: Here, we present the case of a lymphoma patient with previous G6PD deficiency who was admitted to ICU for the treatment of severe pneumonia combined with respiratory failure. PJP was detected by the next-generation sequencing of the bronchoalveolar lavage fluid. The patient was initially treated with the antifungal drug caspofungin; however, this treatment showed poor therapeutic effect. Based on the evaluation of G6PD enzyme activity and the patient's previous history of G6PD deficiency, we finally treated the patient with low-dose TMP-SMX combined with caspofungin and provided rigorous medical care to the patient. Following this treatment, the patient's clinical symptoms improved, lung computed tomography showed reduced pulmonary inflammation, and the fungal ß-(1,3)-D-glucan test (G test) showed decreased levels of fungal D-glucan. After 57 days, the TMP-SMX treatment was discontinued. No symptoms related to G6PD deficiency, such as hemolysis, hematuria, and anemia, occurred during the treatment course. Conclusion: This is the first report mentioning the successful treatment of Pneumocystis jirovecii pneumonia with a double-drug regimen with low-dose TMP-SMX and caspofungin in a T-lymphoblastic leukemia/lymphoma patient with previous G6PD deficiency. Enzyme activity detection is the first step for anti-PJP treatment in patients with G6PD deficiency. Although patients with mild enzyme deficiency may not show any adverse reactions, we still recommend the regular monitoring of the levels of RBCs, hemoglobin, and hematocrit before and after the use of sulfonamides or sulfoxides and other oxidizing drugs in patients with G6PD deficiency. Among other things, early and correct diagnosis of Pneumocystis jirovecii pneumonia in hematological malignancies patients is very important. Relevant oncologists should be alert to the risk of Pneumocystis jirovecii pneumonia in these patients.

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Procypris mera (Lin, 1933), also known as the Chinese ink carp, currently has a second-class protection status in China. Understanding the structure and characteristics of mitochondrial genes provides essential information for resource conservation and phylogenetic studies of P. mera. Here, we sequenced the mitochondrial genomes of three P. mera (WYL1-3) from three sites and performed phylogenetic analysis. The generated three genomes were 16,587 bp in length, comprising 13 protein-coding genes (PCGs), 22 tRNAs, two rRNAs, and two non-coding regions (control region (CR), D-loop, and light-stranded replication start OL), with a preference for codons ending in A or C. The mitochondrial genomes of WYL2 and WYL3 were identical, differing from that of WYL1 by only five single-nucleotide polymorphisms (SNPs). All mitochondrial PCGs had Ka/Ks ratios of less than one, suggesting purifying selection. Phylogenetic tree analysis based on amino acid sequences suggested that the genus Puntioplites is sister to all other genera of the subfamily Cyprinidae of China; the genus Procypris forms a monophyletic group; and the genera Carassioides, Carassius, and Cyprinus form a monophyletic group. This study contributes to our understanding of the phylogenetic relationships in subfamily Cyprininae in China and lays the foundation for resource conservation and management of P. mera.

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This study introduces a novel thermoacoustic (TA) focusing system enhanced by Airy beam-based acoustic metasurfaces, significantly improving acoustic focusing and efficiency. The system integrates a TA emitter, fabricated from carbon nanotube (CNT) films, with a binary acoustic metasurface capable of generating quasi-Airy beams. Through finite element simulations, the system's heat conduction, acoustic focusing, and self-healing properties were thoroughly analyzed. The results demonstrate that the system achieves superior sub-wavelength focusing, tunable focal length via frequency control, and robust self-healing, even in the presence of obstacles. These findings address current limitations in TA emitters and suggest broader applications in medical ultrasound and advanced technology.

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Delta opioid receptor (δOR) plays a pivotal role in modulating human sensation and emotion. It is an attractive target for drug discovery since, unlike Mu opioid receptor, it is associated with low risk of drug dependence. Despite its potential applications, the pharmacological properties of δOR, including the mechanisms of activation by small-molecule agonists and the complex signaling pathways it engages, as well as their relation to the potential side effects, remain poorly understood. In this study, we use cryo-electron microscopy (cryo-EM) to determine the structure of the δOR-Gi complex when bound to a small-molecule agonist (ADL5859). Moreover, we design a series of probes to examine the key receptor-ligand interaction site and identify a region involved in signaling bias. Using ADL06 as a chemical tool, we elucidate the relationship between the ß-arrestin pathway of the δOR and its biological functions, such as analgesic tolerance and convulsion activities. Notably, we discover that the ß-arrestin recruitment of δOR might be linked to reduced gastrointestinal motility. These insights enhance our understanding of δOR's structure, signaling pathways, and biological functions, paving the way for the structure-based drug discovery.

Assuntos

Microscopia Crioeletrônica , Receptores Opioides delta , Receptores Opioides delta/metabolismo , Receptores Opioides delta/agonistas , Receptores Opioides delta/química , Humanos , Animais , Descoberta de Drogas/métodos , Células HEK293 , Transdução de Sinais/efeitos dos fármacos , beta-Arrestinas/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , Camundongos , Ligantes , Ligação Proteica , Masculino , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Sítios de Ligação , Benzamidas/farmacologia , Benzamidas/química , Piperazinas

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OBJECTIVE: To explore clinical effect of modified Chinese-way technique under shoulder arthroscopy in treating massive rotator cuff tears. METHODS: From January 2019 to June 2022, 22 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair with improved Chinese-way technique, including 10 males and 12 females, aged from 46 to 76 years old with an average of(64.14±7.45) years old;the courses of disease ranged from 5 to 14 months with an average of(8.32±2.42) months;19 patients were complete repaired, and 3 patients were partial repaired. Visual analogue scale (VAS) and University of California at Los Angeles (UCLA) scale were used to evaluate pain and function of shoulder joint preoperatively and 1 year postoperatively. Postoperative complications, the integrity of reconstructed tissue structure and the size of subacromial space were observed. RESULTS: All patients were followed up from 12 to 34 months with an average of (17.14±5.93) months. Re-tear were occurred in 4 patients during MRI follow-up, but clinical symptoms of patients were improved significantly and they were satisfied with the treatment, the others were no complications such as incision infection, peripheral nerve injury, loosening and falling off of internal fixation anchors. Preoperative and 1 year after operation VAS were (8.05±1.12) and (1.82±1.50), UCLA scores were (7.45±1.65) and (31.41±2.87) respectively, and the difference was statistically significant (P<0.05). CONCLUSION: The modified Chinese-way technique under shoulder arthroscopy for the massive rotator cuff tear could relieve pain obviously and recovery postoperative function well, with satisfactory curative effect.

Assuntos

Artroscopia , Lesões do Manguito Rotador , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artroscopia/métodos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Resultado do Tratamento

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Antimicrobial peptides (AMPs) are a promising solution for treating antibiotic-resistant pathogens. However, efficient generation of diverse AMPs without prior knowledge of peptide structures or sequence alignments remains a challenge. Here, ProT-Diff is introduced, a modularized deep generative approach that combines a pretrained protein language model with a diffusion model for the de novo generation of AMPs sequences. ProT-Diff generates thousands of AMPs with diverse lengths and structures within a few hours. After silico physicochemical screening, 45 peptides are selected for experimental validation. Forty-four peptides showed antimicrobial activity against both gram-positive or gram-negative bacteria. Among broad-spectrum peptides, AMP_2 exhibited potent antimicrobial activity, low hemolysis, and minimal cytotoxicity. An in vivo assessment demonstrated its effectiveness against a drug-resistant E. coli strain in acute peritonitis. This study not only introduces a viable and user-friendly strategy for de novo generation of antimicrobial peptides, but also provides potential antimicrobial drug candidates with excellent activity. It is believed that this study will facilitate the development of other peptide-based drug candidates in the future, as well as proteins with tailored characteristics.

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BACKGROUND: Osteosarcoma (OS) is a common malignancy among adolescents and children, characterized by a high propensity for metastasis and resistance to chemotherapy. AIMS: This study aimed to investigate the role of COL12A1, a gene often overexpressed in various cancers and associated with poor prognosis, in the progression of OS and explore the underlying mechanisms. METHODS: The expression pattern and potential function of COL12A1 in OS were evaluated using bioinformatics analyses, clinical sample examination, and OS cell lines. Various assays, including transwell, CCK-8, flow cytometry, and wound healing, were performed to assess the impact of COL12A1 on OS cell growth, cell cycle progression, apoptosis, invasion, and migration. Western blot analysis was conducted to investigate markers associated with the FAK/PI3K/AKT/mTOR pathway. RESULTS: COL12A1 expression was significantly elevated in OS tissues and cells. Upregulation of COL12A1 promoted cell growth, accelerated cell cycle progression, and enhanced migration and invasion while inhibiting apoptosis. Conversely, the knockdown of COL12A1 had the opposite effect. Additionally, COL12A1 overexpression increased the phosphorylation of components in the FAK/PI3K/AKT/mTOR pathway. The FAK inhibitor Y15 mitigated the effects of COL12A1 overexpression on cell apoptosis, invasion, proliferation, and the FAK/PI3K/AKT/mTOR pathway in OS. CONCLUSION: Our findings indicated that COL12A1 enhanced OS development by activating the FAK/PI3K/AKT/mTOR pathway, suggesting that COL12A1 could serve as a valuable biomarker for the prediction and identification of OS patients.

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Circular RNAs (circRNAs) lack the 5'-end methylated guanine cap structure and 3' polyadenylate tail structure, classifying it as a non-coding RNA. With the extensive investigation of circRNA, its role in regulating cell death has garnered significant attention in recent years, establishing it as a recognized participant in cancer's biological processes. Autophagy, an essential pathway in programmed cell death (PCD), involves the formation of autophagosomes using lysosomes to degrade cellular contents under the regulation of various autophagy-related (ATG) genes. Numerous studies have demonstrated that circRNA can modulate the biological activity of cancer cells by influencing the autophagy pathway, exhibiting a dualistic role in suppressing or promoting carcinogenesis. In this review, we comprehensively analyze how autophagy-related circRNA impacts the progression of gastrointestinal cancer (GIC). Additionally, we discuss drug resistance phenomena associated with autophagy regulation in GIC. This review offers valuable insights into exploring potential biological targets for prognosis and treatment strategies related to GIC.

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Contemporary research on the walking environment focuses closely on the construction logic and internal correlation. Walkability is one of the vital characteristics of the old town street space. To understand how to improve the old town street space effectively, the investigation of the correlation mechanism of street walkability is essential. This study utilizes structural equation model (SEM) to construct a street walkability measurement model composed of four unobserved factors. Then, take Old Southern Area in Nanjing as an example, integrate Depthmap, ArcGIS and Python to obtain multi-source data, and establish a database of observed factors on street space. Finally, the matrix of the observed factors is set by SEM to calculate the correlation of the unobserved factors. This paper provides a novel technical approach for the correlation study of spatial construction logic as well as a reference for strengthening the spatial quality of the contemporary built environment.

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Objective: The main aim of this study was to evaluate the effect of oral probiotics on the human milk microbiota and determine whether that influenced infant microbiota development. Methods: A total of 27 pregnant women were recruited; 14 were assigned to the probiotic group, and the rest were assigned to the control group. Their infants were likewise assigned to the probiotic group or the control group. Pregnant women in the probiotic group received probiotic supplementation from 32 weeks of gestation until delivery. Human milk samples and infant fecal samples were collected at 6 months after delivery, and 16S rRNA sequencing was used to analyze the composition of the human milk and infant gut microbiota (NCT06241222). Results: In the control group, bacterial microbiota were detected in 8 out of 13 milk samples, whereas in the probiotic group, only 6 out of 14 milk samples contained bacterial microbiota. We examined the composition of the human milk and infant gut microbiota in both the control and probiotic groups. Spearman correlation analysis revealed that various genera in human milk were correlated with the infant gut microbiota. The Linear discriminant analysis effect size (LEfSe) showed that 6 bacteria in the human milk microbiota in the control group were significantly more abundant than those in the probiotic group. Nine bacteria were significantly more abundant in the human milk microbiota in the probiotic group than the control group. According to the LEfSe results, 11 bacteria in the infant gut microbiota in the control group were significantly more abundant than those in the probiotic group. Fourteen bacteria were significantly more abundant in the infant gut microbiota in the probiotic group than in the control group. Conclusion: The infant gut microbiota at 6 months has a complicated relationship with the maternal human milk microbiota. Oral probiotic supplementation can change the composition of the human milk microbiota and the infant gut microbiota.

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Several studies have evaluated the effects of resveratrol supplementation on lipid profile parameters in humans and have demonstrated varying results. We systematically evaluated the literature and performed an umbrella meta-analysis of the effects of resveratrol supplementation on lipid profile. A comprehensive literature search was conducted in the following databases; PubMed, Embase, Scopus, and Web of Science for studies published up to November 2023. According to the standardized mean difference (SMD) analysis, resveratrol supplementation was effective in reducing serum triglyceride (TG) (SMD = -0.14 mg/dl, 95 % CI: -0.24, -0.03; p = 0.001), total cholesterol (TC) (SMD = -0.20, 95 % CI: -0.31, -0.08; p= 0.001), but not high-density lipoprotein cholesterol (HDL-c) (SMD = 0.00, 95 % CI: -0.04, 0.05; p =0.92), and low-density lipoprotein-cholesterol (LDL-c) (SMD = -0.16 mg/dl, 95 % CI: -0.40, 0.07; p =0.17). In the weighted mean difference analysis, resveratrol did not significantly decrease lipid profile parameters. Resveratrol supplementation reduces TC and TG (based on SMD analysis), but it does not significantly affect other indices. However, these significant decreases are not clinically important. Therefore, resveratrol only can be considered as an adjunctive therapeutic approach in managing dyslipidemia.

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Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.

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Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5'-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice.