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A key goal of modern medicine is target-specific therapeutic intervention. However, most drugs lack selectivity, resulting in 'off-target' side effects. To address the requirements of 'targeted therapy,' aptamers, which are artificial oligonucleotides, have been used as novel targeting ligands to construct aptamer drug conjugates ( ApDC) that can specifically bind to a broad spectrum of targets, including diseased cells. Accordingly, the application of aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity. Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery. In this review, we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1438. doi: 10.1002/wnan.1438 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Oil pollution caused by oil spills and oily wastewater has become a global issue. Oil–water separation with help of membrane possessing special wettability is a significant and feasible solution. The special wettability can be achieved by many materials. However, recent researches still have several limits for practical application. Herein, we report a surface of CuO with special microstructure, which is achieved by a simple thermal oxidation treatment of the Cu micro-cone decorated membrane. In the dynamite contact angle test, the CuO micro-cone decorated membrane exhibits higher water affinity than Cu micro-cone decorated membrane and superhydrophilicity with a water contact angle of 0°. In addition, the special micro-cone structure of CuO contributes to high mechanical and thermal stability (up to 400 °C). Furthermore, the CuO micro-cone decorated membrane presents its practical applications for oil–water separation and anti-fouling property for various viscous oils. We believe this membrane with robust stability and superhydrophilicity has great potential for practical applications in oil pollutant treatment. [Display omitted] • A CuO micro-cone decorated membrane is synthesized by a simple and economical method. • The membrane exhibits superhydrophilicity, superior mechanical and thermal stability. • The membrane shows excellent oil–water separation and anti-fouling property. [ABSTRACT FROM AUTHOR]

• DMP@mgel can simultaneously deliver multiple bioactive materials and ensure their proper functionality. • DMP@mgel could address three challenging aspects in the treatment of myocardial injury. • DMP@mgel promotes myocardial cell regeneration by modulating the activity of Hippo pathway. Myocardial ischemia reperfusion (I/R) injury frequently impacts the outcome of patients with coronary heart disease and lacks effective therapeutic strategies. We have summarized the challenges in treating IR injury into three aspects, namely inflammatory reaction, fibrosis, and impaired proliferation ability of myocardial tissue. To address these issues, we have developed an injectable composite microgel called DMP@mgel by integrating three types of biomaterials: placental-derived mesenchymal stem cells loaded microgel, PEDOT:PSS loaded microgel, and siRNA-loaded carrier DP7-C. Upon injection into the injured area, DMP@mgel could regulate the inflammatory microenvironment, promote angiogenesis by the function of stem cells paracrine. Additionally, it enhances coupling between myocardial cells due to its high electrical conductivity. Moreover, DP7-C/siRNA complex can efficiently transfect into myocardial cells to inhibit Hippo pathway activity and promote cell proliferation. The electrostatic interaction enables DP7-C to combine all components into a stable delivery system. In vitro and in vivo experiments confirmed that each ingredient of DMP@mgel exhibits their respective functions such as neovascularization promotion, Hippo pathway inhibition, and antioxidation capability. Finally, administration of DMP@mgel in I/R injured rats significantly improved heart function while reducing fibrosis as evidenced by echocardiography results along with Evans blue staining and histological examination. [ABSTRACT FROM AUTHOR]

Catalyzed diesel particulate filter (CDPF) is the most effective device to control the pollution of particle matter. The regeneration of CDPF is the most important step to maintain efficient work. The combustion kinetics of soot with lubricant-derived ash are investigated over powder and waffle catalysts. The kinetic tests of powder and monolithic mixtures from the engine bench show that the combustion rate constant under 0.25% NO2 is much higher than that under 10% O2. The high combustion rate constants are associated with a low apparent activation energy. Due to the inhibition of the soot–catalyst and soot–NO2 contact, the ash accumulation increases the combustion temperature and decreases the rate constant. Moreover, as the soot particles pack tightly together, the combustion on monolithic CDPF is more difficult than that in the powder mixture. Our study implies that the ash on the CDPF decreases the combustion activity of catalysts in the passive regeneration and affects the triggering of active regeneration controlled by pressure drops. Future development of catalysts needs to focus on uniform porous but stable catalyst layers on CDPF. A practical indicator of effectiveness of such catalysts is the combustion temperature from an engine bench. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the most common chronic autoimmune disease worldwide. Although progress has been made in RA treatment in recent decades, remission cannot be effectively achieved for a considerable proportion of RA patients. Thus, novel potential targets for therapeutic strategies are needed. Semaphorin 5A (SEMA5A) plays a pivotal role in RA progression by facilitating pannus formation, and it is a promising therapeutic target. In this study, we sought to develop an antibody treatment strategy targeting SEMA5A and evaluate its therapeutic effect using a collagen-induced arthritis (CIA) model. We generated SYD12–12, a fully human SEMA5A blocking antibody, through phage display technology. SYD12–12 intervention effectively inhibited angiogenesis and aggressive phenotypes of RA synoviocytes in vitro and dose-dependently inhibited synovial hyperplasia, pannus formation, bone destruction in CIA mice. Notably, SYD12–12 also improved the Treg/Th17 imbalance in CIA mice. We confirmed through immunofluorescence and molecular docking that SYD12–12 integrated with the unique TSP-1 domain of SEMA5A. In conclusion, we developed and characterized a fully human SEMA5A-blocking antibody for the first time. SYD12–12 effectively alleviated disease progression in CIA mice by inhibiting pannus formation and improving the Treg/Th17 imbalance, demonstrating its potential for the RA treatment. [Display omitted] • Novel fully human monoclonal antibodies specific to SEMA5A are developed using phage display technology. • The mAb SYD12-12 potently inhibits angiogenesis in vitro and in vivo. • The mAb SYD12-12 potently reduces the pathogenicity of FLS. • The mAb SYD12-12 inhibits pannus formation and restores Treg/Th17 imbalance in CIA mice. • SYD12-12 integrated with the unique TSP-1 domain of SEMA5A. [ABSTRACT FROM AUTHOR]

Background: Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology. Results: A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis. Conclusion: The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF. [ABSTRACT FROM AUTHOR]

[Display omitted] • α-linolenic acid was seriously deficient in hippocampus of schizophrenic mice. • α-linolenic acid replenishment alleviated cognitive impairment and enhanced synaptic plasticity in mice with SCZ. • α-linolenic acid mitigated microglia-mediated neuroinflammation by suppressing the NF-κB/NLRP3 pathway via binding GPR120-β-arrestin 2. Schizophrenia (SCZ) is a heterogeneous psychiatric disorder that is poorly treated by current therapies. Emerging evidence indicates that SCZ is closely correlated with a persistent neuroinflammation. α-linolenic acid (ALA) is highly concentrated in the brain and represents a modulator of the immune system by decreasing the inflammatory response in chronic metabolic diseases. This study was first designed to investigate the potential role of dietary ALA on cognitive function and neuroinflammation in mice with SCZ. In vivo , after 2 weeks of modeling, mice were treated with dietary ALA treatment for 6 weeks. In vitro , inflammation model was created using lipopolysaccharide as an inducer in BV2 microglial cells. Our results demonstrated that ALA alleviated cognitive impairment and enhanced synaptic plasticity in mice with SCZ. Moreover, ALA mitigated systematic and cerebral inflammation through elevating IL-10 and inhibiting IL-1β, IL-6, IL-18 and TNF-α. Furthermore, ALA notably inhibited microglia and pro-inflammatory monocytes, as well as microglial activation and polarization. Mechanistically, ALA up-regulated the expressions of G protein coupled receptor (GPR) 120 and associated β-inhibitor protein 2 (β-arrestin2), accompanied by observable weakened levels of transforming growth factor-β activated kinase 1 (TAK1), NF-κB p65, cysteine proteinase-1 (caspase-1), pro-caspase-1, associated speck-like protein (ASC) and NLRP3. In vitro , ALA directly restrained the inflammation of microglia by decreasing the levels of pro-inflammatory factors and regulating microglial polarization via GPR120-NF‐κB/NLRP3 inflammasome signaling pathway, whereas AH7614 definitely eliminated this anti-inflammatory effect of ALA. Dietary ALA ameliorates microglia-mediated neuroinflammation by suppressing the NF-κB/NLRP3 pathway via binding GPR120-β-arrestin2. [ABSTRACT FROM AUTHOR]

Stress is known to disrupt the intestinal barrier and induce intestinal dysfunction. A critical role for gonadotropin inhibitory hormone (GnIH) in stress has emerged. However, whether GnIH mediates stress-induced intestinal dysfunction remains unknown. The present study explored this question through in vivo and in vitro experiments in hens. Our in vivo experiments showed that continuous intraperitoneal injection of GnIH not only significantly increased the concentration of stress hormones in serum, but also significantly elevated the mRNA expression of glucocorticoid receptor (GR) in the duodenum and jejunum. Moreover, morphological and molecular analyses revealed that GnIH disrupted the physical and chemical barriers of the intestine and dramatically increased inflammatory factor levels in the intestine and serum of hens. Interestingly, the microbiomics results showed that GnIH altered the structure and composition of the gut flora in the cecum, revealing an increased abundance of harmful intestinal bacteria such as Desulfovibrionaceae. Similar results were found in in vitro studies in which the GnIH-induced intestinal mucosal barrier was disrupted, and inflammation increased in jejunal explants, although no significant difference was found in the expression of GR between the control and GnIH groups. Our results demonstrated that GnIH not only directly damaged intestinal barriers and elevated intestinal inflammation but also mediated stress and microflora imbalance-induced intestinal function disorder, suggesting that GnIH is a potential therapeutic target for gut dysfunction, stress-induced intestinal function disorder, and inflammatory bowel disease in animals and humans. [ABSTRACT FROM AUTHOR]

Thanks to the advancements in bioinformatics, drugs, and other interventions that modulate microbes to treat diseases have been emerging continuously. In recent years, an increasing number of databases related to traditional Chinese medicine (TCM) or gut microbes have been established. However, a database combining the two has not yet been developed. To accelerate TCM research and address the traditional medicine and micro ecological system connection between short board, we have developed the most comprehensive micro-ecological database of TCM. This initiative includes the standardization of the following advantages: (1) A repeatable process achieved through the standardization of a retrieval strategy to identify literature. This involved identifying 419 experiment articles from PubMed and six authoritative databases; (2) High-quality data integration achieved through double-entry extraction of literature, mitigating uncertainties associated with natural language extraction; (3) Implementation of a similar strategy aiding in the prediction of mechanisms of action. Leveraging drug similarity, target entity similarity, and known drug-target entity association, our platform enables the prediction of the effects of a new herb or acupoint formulas using the existing data. In total, MicrobeTCM includes 171 diseases, 725 microbes, 1468 herb-formulas, 1032 herbs, 15780 chemical compositions, 35 acupoint-formulas, and 77 acupoints. For further exploration, please visit https://www.microbetcm.com. [Display omitted] [ABSTRACT FROM AUTHOR]

Embryology provides an understanding of individual's origin and developmental patterns. Turtles are among the oldest living reptiles and have unique body structure. However, the morphogenesis and mechanisms of turtles are not fully understood. In this study, we focused on the embryonic development of red-eared slider (Trachemys scripta elegans) which widely distributes in the world. At an incubation temperature of 28 °C, the turtle eggs had a 61-day incubation cycle, and the entire embryonic development process was divided into 27 stages and 3 phases according to variations in age, body size, and morphological characteristics. The early phase of embryonic development (the first 12 stages) were characterized by embryo growth, and the appearance of internal organ precursors. The middle phase (stages 13–20) involved prominent heart division at stage 13 and the appearance of carapace and plastron at stages 14 and 17, respectively. In the later phase (stages 21–27), the hatchlings formed, and the carapace and plastron thickened. Transcriptome analysis of embryos showed enrichment of the differential genes in pathways related to development, metabolism, disease, and cellular processes. The Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analysis implied the crucial regulatory role of the axon guidance pathway. Real-time fluorescence quantitative PCR indicated upregulated expression of wnt5a and bmp7 in stages 7 and 16 compared to that in stage 12. This study revealed the development process of red-eared slider embryo and the dynamics of the signaling pathway affecting its development, which supplemented the theory of embryo development, and provided new ideas for the molecular mechanism of turtle embryo development. • The morphological changes in embryonic development of the red-eared turtle are described. • Turtle embryonic development is divided into 27 stages and 3 phases. • Wnt5a and Bmp7 play key roles in regulating axon guidance. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most ordinary type of thyroid cancer. Studies pivoting on the mechanisms of microRNAs (miRNAs) are adequately explored but not much on miR-448 in PTC. Thus, this study is proposed to bring forward the uncovered mechanisms of miR-448 in PTC. Lysine specific demethylase 5B (KDM5B), miR-448 and transforming growth factor β-induced factor 1 (TGIF1) expression in PTC tissues and cell lines were detected. The connection between miR-448 expression and clinicopathological characteristics of PTC patients was determined. PTC cell lines TPC-1 and K-1 were transfected with sh-KDM5B, si-TGIF1 or miR-448 mimic to explore their roles in PTC cell progression. Tumor xenografts in nude mice was performed to detect tumor volume and weight. KDM5B and TGIF1 were increased and miR-448 was declined in PTC tissues and cell lines. MiR-448 expression was connected with N stage, lymph node metastasis and advanced tumor node metastasis stage of PTC patients. KDM5B knockdown or TGIF1 reduction or miR-448 elevation undermined PTC cell progression and inhibited tumor growth of nude mice. Down-regulation of miR-448 followed by KDM5B knockdown reversed the effect of decreased KDM5B on the proliferation inhibition and apoptosis promotion of PTC cells. Our study elaborates that KDM5B-mediated miR-448 up-regulation restrains PTC cell progression and slows down tumor growth via TGIF1 repression, which provides a novel reference for treatment of PTC. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a terrible microvascular disorder causing blindness. Retinal inflammation is the early stage in DR, which is believed to play a crucial role in the development of it. Shengpuhuang-tang (ST), a traditional herbal formula, which has effective treatment of fundus bleeding disorder. ST exerts protective effects against DR in rats, but its underlying mechanism of this efficacy remains unknown. Thus, the objective of this study is to examine the mechanism and the efficacy of ST on retinal inflammation in streptozotocin-induced diabetic rats. The administration of ST was initiated at 4 weeks after diabetes induction and continued for 12 weeks. Retinal vessel permeability was evaluated by using FITC-dextran and Evans blue. Retinal leukostasis was evaluated with FITC-coupled concanavalin A lectin (ConA). Moreover, western blotting was performed to detect TNF-α, ICAM-1 and the relative expression levels of IκBα, IKKβ, and p65 in vivo. The results showed that the retinal inflammation in streptozotocin-induced diabetic rats was significantly decreased by ST. ST could decreased the expression levels of TNF-α, ICAM-1 and inhibited the expression of p-IKKβ, p-p65 and IκBα. It could also inhibited the nuclear transfer of p65. In conclusion, these data suggested that ST may have potential treatment strategies against early stage of diabetic retinopathy through NF-κB pathway. Image 1 [ABSTRACT FROM AUTHOR]

Dioscorea composita (D. composita) is a perennial herb with abundant steroidal saponins that have gained worldwide attention for their remarkable efficacy in cardiovascular diseases. However, few studies have been worked on the regulatory network of steroidal saponins biosynthesis under phytohormone induced. In this study, we combined the transcriptome and metabolome analysis to reveal the variation of diosgenin and steroidal saponins in transcriptional and metabolism levels under methyl-jasmonate (MeJA) treatment. Although the application of MeJA indeed significantly increased the accumulation of diosgenin of D. composita, different types of steroidal saponins exhibited different accumulation patterns. Consistently, the expression levels of UDP-glycosyltransferases and Cytochrome P450 monooxygenases genes that highly related to the accumulation of steroidal saponins were either up- or down-regulated. Correlation analyses of transcription factors (TFs)-steroidal saponins and structural genes-TFs were further to identified the TFs potentially involved in the regulation of steroidal saponins biosynthesis. Silencing of DcWRKY11 in Dioscorea composita decreases the accumulation of steroidal saponins by regulating the expression steroidal saponins synthesis genes, suggesting that DcWRKY11 is a positive regulator in the regulation of steroidal saponins biosynthesis. Our findings take a deeper understanding of the regulatory network of MeJA-mediated steroidal saponins biosynthesis in D. composita., Competing Interests: Declaration of competing interest We declare that we have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

To investigate the factors influencing glycemic control in gestational diabetes mellitus (GDM) patients and their impacts on pregnancy outcomes, providing insights for GDM management. Pregnant women diagnosed with GDM at a tertiary hospital in western China in 2019. Participants were categorized based on varying levels of glycemic control during pregnancy. A retrospective analysis was conducted, utilizing univariate and multivariate regression analyses, to identify factors influencing glycemic control in GDM patients. Based on various approaches to manage glucose, subjects were categorized into A1 (diet and exercise guidance alone) and A2 (insulin usage) groups. Based on whether glucose levels met the glycemic target in women with GDM, subjects were further divided into satisfactory and unsatisfactory groups. A total of 2621 women meeting the inclusion criteria were enrolled in the study. Independent factors associated with GDM A2 included higher prepregnancy body mass index (odds ratio [OR] = 1.070, 95% confidence interval [CI]: 1.019-1.122, P = .006), a history of GDM (OR = 1.888, 95% CI: 1.052-3.389, P = .033), elevated fasting plasma glucose (FPG) in early pregnancy (OR = 1.828, 95% CI: 1.320-2.532, P < .001), elevated 1-hour postprandial glucose (1-h PG) (OR = 1.126, 95% CI: 1.0091.256, P = .034), and 2-h PG by oral glucose tolerance test (OGTT) (OR = 1.181, 95% CI: 1.046-1.333, P = .007). Higher FPG by OGTT was an independent risk factor for unsatisfactory glycemic control (OR = 1.590, 95% CI: 1.273-1.985, P < .001). Compared with the A1 group, the A2 group has longer hospitalization, higher rates of cesarean section, placenta previa, and neonatal pneumonia (P < .05). Compared with the satisfactory group, the unsatisfactory group has lower gestational age, lower rates of cesarean section and placenta previa, and higher rates of postpartum hemorrhage for mothers; lower length and weight, and higher rates of premature birth, jaundice, hypoglycemia, pneumonia, respiratory distress syndrome, anemia, hospitalization, and hospitalization for more than 15 days in both pediatric unit and neonatal intensive care unit for newborns (P < .05). Elevated prepregnancy body mass index, FPG in early pregnancy, 1-h and 2-h PG during OGTT, and with a history with GDM are independent factors influencing insulin utilization, while elevated 0-h PG is an independent influencing factor of unsatisfactory glycemic control. Poor glycemic control has negative impacts on both maternal and fetal outcomes under 2 classifications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Phoxim, extensively utilized in agriculture as an organothiophosphate insecticide, has the potential to cause neurotoxicity and pose human health hazards. In this study, an electrochemical enzyme biosensor based on Ti 3 C 2 MXene/MoS 2 @AuNPs/AChE was constructed for the sensitive detection of phoxim. The two-dimensional multilayer structure of Ti 3 C 2 MXene provides a robust framework for MoS 2 , leading to an expansion of the specific surface area and effectively preventing re-stacking of Ti 3 C 2 MXene. Additionally, the synergistic effect of self-reduced grown AuNPs with MoS 2 further improves the electrical conductivity of the composites, while the robust framework provides a favorable microenvironment for immobilization of enzyme molecules. Ti 3 C 2 MXene/MoS 2 @AuNPs electrochemical enzyme sensor showed a significant response to phoxim in the range of 1 × 10 -13  M to 1 × 10 -7  M with a detection limit of 5.29 × 10 -15  M. Moreover, the sensor demonstrated excellent repeatability, reproducibility, and stability, thereby showing its promising potential for real sample detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Currently, immunotherapy is being widely used for treating cancers. However, the significant heterogeneity in patient responses is a major challenge for its successful application. CD8-positive T cells (CD8 + T cells) play a critical role in immunotherapy. Both their infiltration and functional status in tumors contribute to treatment outcomes. Therefore, accurate monitoring of CD8 + T cells, a potential biomarker, may improve therapeutic strategy. Positron emission tomography (PET) is an optimal option which can provide molecular imaging with enhanced specificity. This review summarizes the mechanism of action of CD8 + T cells in immunotherapy, and highlights the recent advancements in PET-based tracers that can visualize CD8 + T cells and discusses their clinical applications to elucidate their potential role in cancer immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Du, Wang, Cui, Wang, Zhao, Li and Li.)

Diabetic cardiomyopathy (DCM) is a myocardial-specific microvascular disease caused by diabetes that affects the structure and function of the heart and is considered to be the leading cause of morbidity and death in patients with diabetes. Currently, there is no specific treatment or preventive drug for DCM, and there is an urgent need to develop new drugs to treat DCM. Traditional Chinese medicine (TCM) has rich experience in the treatment of DCM, and its characteristics of multi-target, multi-pathway, multi-component, and few side effects can effectively deal with the complexity and long-term nature of DCM. Growing evidence suggests that myocardial fibrosis, inflammation, oxidative stress, apoptosis, cardiac hypertrophy, and advanced glycation end product deposition were the main pathologic mechanisms of DCM. According to the pathological mechanism of DCM, this study revealed the potential of metabolites and prescriptions in TCM against DCM from the perspective of signaling pathways. The results showed that TGF-β/Smad, NF-κB, PI3K/AKT, Nrf2, AMPK, NLRP3, and Wnt/β-catenin signaling pathways were the key signaling pathways for TCM treatment of DCM. The aim of this study was to summarize and update the signaling pathways for TCM treatment of DCM, to screen potential targets for drug candidates against DCM, and to provide new ideas and more experimental evidence for the clinical use of TCM treatment of DCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Liu, Liu, Xing, Liu, Wu, Hu and Zhang.)

Mesenchymal stem cell (MSC)-based therapy is an effective strategy for regenerative therapy. However, safety and ease of use are still issues to be overcome in clinical applications. Exosomes are naturally derived nanoparticles containing bioactive molecules, which serve as ideal cell-free therapeutic modalities. However, issues such as delivery, long-term preservation and activity maintenance of exosomes are other problems that limit their application. In this study, we proposed the use of rapid freeze-dry-thaw macroporous hydrogels for the encapsulation of HucMSC-derived exosomes (HucMSC-Exos) combined with an antimicrobial peptide coating. This exosome-encapsulated hyaluronic acid macroporous hydrogel HD-DP7/Exo can achieve long-term storage and transport by lyophilization and can be rapidly redissolved for treatment. After comprehensively comparing the therapeutic effects of HucMSC-Exos and HucMSC-loaded hydrogels, we found that HucMSC-Exos could also effectively regulate fibroblasts, vascular endothelial cells, and macrophages and inhibit myofibroblast-mediated fibrosis, thus promoting tissue regeneration and inhibiting scar formation in a mouse model of deep second-degree burn infection healing. These properties of lyophilized storage and whole-process-repair make HD-DP7/Exo have potential application value and application prospects., Competing Interests: Declaration of competing interest The authors declare that they have no competition of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Context: Helicobacter pylori ( H. pylori ), a spiral-shaped bacterium, is closely associated with chronic, progressive gastric mucosal damage, gastric atrophy, and even gastric cancer (GC). An increasing number of studies have addressed the correlation between long noncoding RNAs (lncRNAs) and H. pylori pathogenicity in GC., Objective: In this study, we found that the expression level of LINC00659 gradually increased in the progression from atrophic gastritis, intestinal metaplasia, and dysplasia to GC in H. pylori -infected patients. Thus, we aimed to further explore the function of LINC00659 in the progression of gastritis to cancer under H. pylori infection., Materials and Methods: StarBase predictions, ribonucleic acid (RNA)-binding protein immunoprecipitation assays, and gene ontology functional annotation (GO)/Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to identify the RNA-binding proteins of LINC00659; moreover, qRT‒PCR, western blotting, RNA interference, and immunofluorescence assays were used to investigate the function of LINC00659., Results: LINC00659 bound directly to the RNA-binding protein polypyrimidine tract-binding protein (PTBP1). Importantly, qRT‒PCR and western blot assays demonstrated that PTBP1 expression increased in the progression from inflammation to cancer in the stomach of H. pylori -infected patients and H. pylori -infected GES-1 cells. However, LINC00659 knockdown downregulated PTBP1 expression and inhibited PTBP1 binding under H. pylori infection. Finally, LINC00659 knockdown significantly reduced H. pylori -induced human gastric epithelial cell senescence and suppressed interleukin (IL)-6 and IL-8 secretion by reducing the phosphorylation level of NF-κB p65., Conclusions: This study indicated that LINC00659 may have the potential to be a novel promising prognostic and therapeutic marker for H. pylori -associated gastric diseases., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Objective: This research aimed to elucidate the relationship between testosterone levels and serum soluble klotho (S-klotho) concentrations in females aged 40-79 years using the National Health and Nutrition Examination Survey (NHANES) dataset., Design: Associations between testosterone and S-klotho were assessed through multivariable linear regression methodologies, spanning nonadjusted, minimally adjusted, and fully adjusted models., Settings: The investigation was conducted as a cross-sectional analysis utilizing the NHANES database., Participants: From 20,146 NHANES participants between 2013 and 2016, 2,444 females met the stipulated inclusion and exclusion criteria., Results: Free androgen index (FAI) showcased a negative correlation with S-klotho levels across all regression models (nonadjusted: β -7.08, 95% CI -13.39- -0.76; minimally adjusted: β -9.73, 95% CI -16.6- -2.84; fully adjusted: β -7.63, 95% CI -14.75-0.51). Conversely, total testosterone did not exhibit significant associations with S-klotho across the models. In the nonadjusted model, estradiol was positively associated with S-klotho concentrations (β 0.14, 95% CI 0.05-0.23), but this significance was not retained in subsequent regression models., Conclusion: Findings suggest that in U.S. females aged 40-79 years, FAI negatively correlates with S-klotho concentrations, while there is the lack of significant associations for total testosterone and estradiol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Zhang, Hao, Du, Ao, Zhu and Huang.)

Objective: The purpose of this study is to explore the change in physicians' hypertension treatment behavior before and after the reform of the capitation in county medical community., Methods: Spanning from January 2014 to December 2019, monthly data of outpatient and inpatient were gathered before and after the implementation of the reform in April 2015. We employed interrupted time series analysis method to scrutinize the instantaneous level and slope changes in the indicators associated with physicians' behavior., Results: Several indicators related to physicians' behavior demonstrated enhancement. After the reform, medical cost per visit for inpatient exhibited a reverse trajectory (-53.545, 95%CI: -78.620 to -28.470, p < 0.01). The rate of change in outpatient drug combination decelerated (0.320, 95%CI: 0.149 to 0.491, p < 0.01). The ratio of infusion declined for both outpatient and inpatient cases (-0.107, 95%CI: -0.209 to -0.004, p < 0.1; -0.843, 95%CI: -1.154 to -0.532, p < 0.01). However, the results revealed that overall medical cost per visit and drug proportion for outpatient care continued their initial upward trend. After the reform, the decline of drug proportion for outpatient care was less pronounced compared to the period prior to the reform, and length of stay also had a similar trend., Conclusion: To some extent, capitation under the county medical community encourages physicians to control the cost and adopt a more standardized diagnosis and treatment behavior. This study provides evidence to consider the impact of policy changes on physicians' behavior when designing payment methods and healthcare systems aimed at promoting PHC., (© 2024. The Author(s).)

Objective: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with limited options for reversing its middle-to-late stages. Early intervention is crucial to slow down disease progression. This study aimed to investigate the potential of the NeuroProtect (NP) formula, a combination of geniposide and Panax notoginseng saponins, in preventing AD. We evaluated the effects of the NP formula on amyloid plaque accumulation, neuronal degeneration, and molecular signaling pathways using in vivo and in vitro models., Methods: To predict functional pathways and potential downstream targets of NP intervention, we employed network pharmacology. The preventative impact of the NP formula was assessed using APP/PS1 mice. We conducted HE staining, ELISA assay, Golgi staining, and immunohistochemistry to detect the protective effect of NP. Additionally, cell experiments were performed to assess cell activity and target protein expression., Results: Network pharmacology analysis revealed 145 drug-disease interactions and identified 5 core active targets associated with AD. Molecular docking results demonstrated strong binding affinity between the components of the NP formula (GP, GN-Rb1, GN-Rg1, NS-R1) and target proteins (STAT3, HIF1A, TLR4, mTOR, VEGFA). Notably, the binding energy between NS-R1 and mTOR was -11.4kcal/mol. Among the top 10 enriched KEGG pathways, the HIF-1 and PI3K-AKT signaling pathways were highlighted. In vivo experiments demonstrated that the NP formula significantly ameliorated pathological changes, decreased the Aβ42/Aβ40 ratio in the hippocampus and cortex, and increased dendritic spine density in the CA1 region during the early stage of AD. In vitro experiments further illustrated the NP formula's ability to reverse the inhibitory effects of Aβ25-35 on cell viability and regulate the expression of Tlr4, Mtor, Hif1a, Stat3, and Vegfa., Conclusion: Our findings suggest that NP exhibits neuroprotective effects during the early stages of AD, positioning it as a potential candidate for AD prevention. The NP formula may exert its preventive effects through the HIF-1/PI3K-AKT signaling pathway, with mTOR identified as a key target., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Daily use of passenger vehicles leads to considerable emission of volatile organic compounds (VOCs), which are key precursors to the ground-level ozone pollution. While evaporative and tailpipe emission of VOCs from the passenger vehicles can be eliminated largely, or even completely, by electrification, VOCs emission from the use of coatings in auto-repair is unavoidable and has long been ignored. Here, we present for the first time, to the best of our knowledge, a comprehensive investigation on the emission factors and process-specified characteristics of VOCs from auto-repair painting, based on field measurements over 15 representative auto-repair workshops in the Pearl-River-Delta area, China. Replacement of solvent-borne coatings with water-borne counterparts, which was only achieved partially in the Basecoat step but not in the Putty, Primer and Clearcoat steps, could reduce the per automobile VOCs emission from 756.5 to 489.6 g and the per automobile ozone formation potential (OFP) from 2776.5 to 1666.4 g. Implementation of exhaust after-treatment led to a further reduction of the per automobile VOCs emission to 340.9 g, which is still ca. 42% higher than that from the state-of-art painting processes for the manufacture of passenger vehicles. According to the analysis of VOCs compositions, the Putty process was dominated by the emission of styrene, while Primer, Basecoat (solvent-borne) and Clearcoat steps were all characterized by the emission of n-butyl acetate and xylenes. By contrast, water-borne Basecoat step showed a prominent emission of n-amyl alcohol. Notably, for the full painting process to repair an automobile, n-butyl acetate emerged as the most abundant species in the VOCs emission, whereas xylenes contributed most significantly to the OFP. Scenario analysis suggested that reducing VOCs contents in the coatings, as well as improving the after-treatment efficiency, were highly potential solutions for effective reduction of VOCs emission from auto-repair. Our study contributes to an update of industrial inventories of VOCs emission, and may provide valuable insights for reducing VOCs emission and OFPs from the auto-repair industry., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hailin Xiao reports financial support was provided by National Natural Science Foundation of China and Science and Technology Program of Guangzhou. Peirong Chen reports financial support was provided by Department of Science and Technology of Guangdong Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This article systematically explores the imaging and clinical characteristics of a relatively rare cardiac anomaly: the right coronary artery originating from the left coronary sinus. Through a comprehensive analysis of existing literature, this study aims to provide a comprehensive understanding of the prevalence, diagnostic methods, and potential clinical implications of this anatomical variation. Anatomical classification is introduced, along with clinical imaging diagnostic methods, including coronary angiography, computed tomography, and magnetic resonance imaging. Additionally, the review delves into the clinical significance of this anomaly, including its potential associations with myocardial ischemia, arrhythmias, and acute cardiac events, outlining clinical approaches to diagnosing myocardial ischemia. The study results consolidate current knowledge about this cardiac variation, emphasizing the importance of recognizing and appropriately managing it in clinical practice., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Afterglow materials with time-dependent color output emerge as huge prospects in advanced optical information encryption but remain a formidable challenge due to the limited exciton transfer from a single emission center. Here, multiple time-dependent afterglow color evolutions are achieved by the strategy of controllable assembly of dual carbon dots (CDs) with an individual afterglow color and decay rate into an RHO zeolite. The strategy possesses high controllability such that B-CDs and G-CDs can be independently generated and in situ embedded into a matrix; in particular, the doped amount of two kinds of CDs can be adjusted conveniently to produce interesting variable afterglow colors. Triggered by different excitations, the prepared B&G-CDs@RHO composites exhibit the conversion of TADF and RTP behaviors, as well as time-dependent afterglow color output from deep-blue to green (365 nm excitation) and static cyan (254 nm excitation). The unique luminescence and excellent stability allow the composite applied in information encryption with high-security levels.

Background: Presenilin (PSEN, PS) is essential for γ-secretase function, and mutations can disrupt amyloid-β (Aβ) production in familial Alzheimer's disease. Targeting γ-secretase is complex due to its broad involvement in physiological processes., Objective: Our aim was to create a novel knockin (KI) mouse model expressing PSEN1 D385A mutation and investigate the efficacy of a Geniposide and Ginsenoside Rg1 combination (NeuroProtect modified formula, NP-2) in restoring γ-secretase activity., Methods: Using gene manipulation, we established the PS1 D385A KI mouse model and confirmed the mutation, mRNA, and protein levels using Southern blotting, northern blotting, and western blotting, respectively. In vitro γ-secretase assay was conducted to measure γ-secretase activity, while histological analyses examined neurogenesis effects. NP-2 administration evaluated its impact on γ-secretase activity., Results: The PS1 D385A KI homozygotes displayed severe cerebral hemorrhage, postnatal lethality, developmental disorders, reduced proliferation of neural progenitor cells, and disrupted γ-secretase function. The mutation abolished PS1 protein self-shearing, leading to compromised γ-secretase activity. NP-2 intervention effectively restored γ-secretase activity in the heterozygous mice., Conclusions: PS1 D385A mutant disrupted PS1 protein self-cleaving, impairing γ-secretase activity in KI mice. NP-2 restored γ-secretase function, offering potential for novel AD treatment strategies despite the challenges posed by γ-secretase's complex role in physiological processes.

Background: Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), frequently causes side effects when used to treat non-small cell lung cancer., Objective: The purpose of this experiment was to investigate the side effect of gefitinib on the skin and colon of mice., Methods: Male Balb/c nu-nu nude mice aged 4-5 weeks were used as xenograft tumor models, and gefitinib at 150 mg/kg and 225 mg/kg was started at 9 days after the xenograft tumor grew out. The mice's weights and tumor volumes were tracked concurrently, and the mouse skin adverse reactions and diarrhea were observed during the treatment. The animal tissues were subjected to biochemical and pathological evaluations after 14 days., Results: Gefitinib effectively decreased the size and weight of transplanted tumors in nude mice, while also lowering body weight and raising indexes of the liver and spleen. Gefitinib could cause skin adverse reactions and diarrhea in mice. Further pathological investigation revealed tight junction- related markers in the mice's skin and colon to be reduced and macrophages and neutrophils to be increased after gefitinib treatment., Conclusion: The findings imply that gefitinib has negative effects on the skin and colon. Gefitinib- induced skin and colon adverse reactions in mice have been successfully modeled in this study., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Medical costs have been rising rapidly in recent years, and China is controlling medical costs from the perspective of health insurance payments., Objectives: To explore the impact of the capitation prepayment method on medical expenses and health service utilization of coronary heart disease (CHD) patients, which provides a scientific basis for further improvement of the payment approach., Methods: The diagnosis records of visits for CHD in the database from 2014 to 2016 (April to December each year) were selected, and two townships were randomly selected as the pilot and control groups. Propensity score matching (PSM) and difference-in-difference (DID) model were used to assess changes in outpatient and inpatient expenses and health service utilization among CHD patients after the implementation of the capitation prepayment policy., Results: There were eventually 3,900 outpatients and 664 inpatients enrolled in this study after PSM. The DID model showed that in the first year of implementing the reform, total outpatient expenses decreased by CNY 13.953, drug expenses decreased by CNY 11.289, as well as Medicare payments decreased by CNY 8.707 in the pilot group compared to the control group. In the second year of implementing the reform, compared with the control group, the pilot group had a reduction of CNY 3.123 in other expenses, and a reduction of CNY 6.841 in Medicare payments. There was no significant change in inpatient expenses in the pilot group compared to the control group, but there was an increase of 0.829 visits to rural medical institutions, and an increase of 0.750 visits within the county for inpatients., Conclusions: The capitation prepayment method has been effective in controlling the outpatient expenses of CHD patients, as well as improving the medical service capacity of medical institutions within the Medical Community, and increasing the rate of inside county visits for inpatients., (© 2023. The Author(s).)

Background: To evaluate the association between gestational weight gain (GWG) and preterm birth and post-term birth., Methods: This longitudinal-based research studied singleton pregnant women from the National Vital Statistics System (NVSS) (2019). Total GWG (kg) was converted to gestational age-standardized z scores. The z-scores of GWG were divided into four categories according to the quartile of GWG, and the quantile 2 interval was used as the reference for the analysis. Univariate and multivariate logistic regression analyses were performed to investigate the association between GWG and preterm birth, post-term birth, and total adverse outcome (preterm birth + post-term birth). Subgroup analysis stratified by pre-pregnancy body mass index (BMI) was used to estimate associations between z-scores and outcomes., Results: Of the 3,100,122 women, preterm birth occurred in 9.45% (292,857) population, with post-term birth accounting for 4.54% (140,851). The results demonstrated that low GWG z-score [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.03 to 1.05, P < 0.001], and higher GWG z-scores (quantile 3: OR: 1.42, 95% CI: 1.41 to 1.44, P < 0.001; quantile 4: OR: 2.79, 95% CI: 2.76 to 2.82, P < 0.001) were positively associated with preterm birth. Low GWG z-score (OR: 1.18, 95% CI: 1.16 to 1.19, P < 0.001) was positively associated with an increased risk of post-term birth. However, higher GWG z-scores (quantile 3: OR: 0.84, 95% CI: 0.83 to 0.85, P < 0.001; quantile 4: 0.59, 95% CI: 0.58 to 0.60, P < 0.001) was associated with a decreased risk of post-term birth. In addition, low GWG z-score and higher GWG z-scores were related to total adverse outcome. A subgroup analysis demonstrated that pre-pregnancy BMI, low GWG z-score was associated with a decreased risk of preterm birth among BMI-obesity women (OR: 0.96, 95% CI: 0.94 to 0.98, P < 0.001)., Conclusion: Our result suggests that the management of GWG may be an important strategy to reduce the number of preterm birth and post-term birth., (© 2023. The Author(s).)

By 2040, ~100 million people will have glaucoma. To date, there are a lack of high-efficiency glaucoma diagnostic tools based on visual fields (VFs). Herein, we develop and evaluate the performance of 'iGlaucoma', a smartphone application-based deep learning system (DLS) in detecting glaucomatous VF changes. A total of 1,614,808 data points of 10,784 VFs (5542 patients) from seven centers in China were included in this study, divided over two phases. In Phase I, 1,581,060 data points from 10,135 VFs of 5105 patients were included to train (8424 VFs), validate (598 VFs) and test (3 independent test sets-200, 406, 507 samples) the diagnostic performance of the DLS. In Phase II, using the same DLS, iGlaucoma cloud-based application further tested on 33,748 data points from 649 VFs of 437 patients from three glaucoma clinics. With reference to three experienced expert glaucomatologists, the diagnostic performance (area under curve [AUC], sensitivity and specificity) of the DLS and six ophthalmologists were evaluated in detecting glaucoma. In Phase I, the DLS outperformed all six ophthalmologists in the three test sets (AUC of 0.834-0.877, with a sensitivity of 0.831-0.922 and a specificity of 0.676-0.709). In Phase II, iGlaucoma had 0.99 accuracy in recognizing different patterns in pattern deviation probability plots region, with corresponding AUC, sensitivity and specificity of 0.966 (0.953-0.979), 0.954 (0.930-0.977), and 0.873 (0.838-0.908), respectively. The 'iGlaucoma' is a clinically effective glaucoma diagnostic tool to detect glaucoma from humphrey VFs, although the target population will need to be carefully identified with glaucoma expertise input., Competing Interests: Competing interestsD.T. is the co-inventor of a few patents for deep learning systems on eye diseases. X.Z. and Y.Q. are the co-inventors of patents for deep learning system on glaucoma diagnosis. The other authors declare no competing interests., (© The Author(s) 2020.)

Background: The purpose of this study was to explore the status of prevention and nursing on venous thromboembolism (VTE) among perioperative patients with lung cancer in Chinese hospital., Methods: A self-designed questionnaire was used to investigate 108 head nurses from tertiary hospitals during the first West China Forum on Chest Enhanced Recovery After Surgery (ERAS)., Results: (1) Current status of assessment tools and prevention guidelines: 97.22% of the hospitals have carried out VTE risk assessments for surgical patients with lung cancer, 67.59% of the hospitals have established the nursing prevention specifications of VTE. (2) Current status of screening, precaution and follow-up: 56.48% of the hospitals have taken different approach to screen VTE for lung cancer patients in pre-operative period. 90.74% of the hospitals and 52.78% of the hospitals had VTE prophylaxis for hospitalized and discharged patients, but only 17.59% of hospitals were followed up on the incidence of VTE for discharged patients. (3) There was no statistically significant difference in VTE prevention between different type hospitals (P>0.05). But, all patients in the specialist hospital have been fully implemented on VTE risk assessment and VTE prevention (100.00%)., Conclusions: The clinical staff have already realized the importance of VTE prevention, and the VTE prevention in perioperative patients with lung cancer has received extensive attention. But there is still lack of effective risk assessment tools and standardized guidelines of VTE prevention.

A key goal of modern medicine is target-specific therapeutic intervention. However, most drugs lack selectivity, resulting in 'off-target' side effects. To address the requirements of 'targeted therapy,' aptamers, which are artificial oligonucleotides, have been used as novel targeting ligands to construct aptamer drug conjugates (ApDC) that can specifically bind to a broad spectrum of targets, including diseased cells. Accordingly, the application of aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity. Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery. In this review, we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1438. doi: 10.1002/wnan.1438 For further resources related to this article, please visit the WIREs website., (© 2016 Wiley Periodicals, Inc.)