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The structures and properties of the composite films formed by soy protein isolate (SPI) and xanthan gum (XG) with different other matrices were investigated. The composite films were prepared with SPI and XG by adding sodium alginate (SA), carboxymethyl cellulose (CMC), gelatin (GEL), pectin (PEC) and agar (Agar), respectively. The thickness, mechanical properties, oxygen permeability and opacity of the composite films were measured, and their structures were characterized. The results showed that the thicknesses of composite films with 1.5 g of different other matrices were significantly higher (P

In the field of cancer therapy, inhibiting autophagy has emerged as a promising strategy. However, pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1 (PD-L1), enabling tumor immune evasion. To address this issue, we developed innovative ROS-responsive cationic poly(ethylene imine) (PEI) nanogels using selenol chemistry-mediated multicomponent reaction (MCR) technology. This procedure involved simple mixing of low-molecular-weight PEI (LMW PEI), γ-selenobutylacetone (γ-SBL), and poly(ethylene glycol) methacrylate (PEGMA). Through high-throughput screening, we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels, which exhibited a size of approximately 200 nm, excellent colloidal stability, and the most effective PD-L1 silencing efficacy. These nanogels demonstrated enhanced uptake by tumor cells, excellent oxidative degradation ability, and inhibited autophagy by alkalinizing lysosomes. The A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I (MHC-I), resulting in robust proliferation of specific CD8+ T cells and a decrease in MC38 tumor growth. As a result, the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy, upregulation of MHC-I, and downregulation of PD-L1. Designed with dynamic diselenide bonds, the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.

Although several synthetic hydrogels with defined stiffness have been developed to facilitate the proliferation and maintenance of human pluripotent stem cells (hPSCs), the influence of biochemical cues in lineage-specific differentiation and functional cluster formation has been rarely reported. Here, we present the application of Supragel, a supramolecular hydrogel formed by synthesized biotinylated peptides, for islet-like cluster differentiation. We observed that Supragel, with a peptide concentration of 5 mg/mL promoted spontaneous hPSCs formation into uniform clusters, which is mainly attributable to a supporting stiffness of ∼1.5 kPa as provided by the Supragel matrix. Supragel was also found to interact with the hPSCs and facilitate endodermal and subsequent insulin-secreting cell differentiation, partially through its components: the sequences of RGD and YIGSR that interacts with cell membrane molecules of integrin receptor. Compared to Matrigel and suspension culturing conditions, more efficient differentiation of the hPSCs was also observed at the stages 3 and 4, as well as the final stage toward generation of insulin-secreting cells. This could be explained by 1) suitable average size of the hPSCs clusters cultured on Supragel; 2) appropriate level of cell adhesive sites provided by Supragel during differentiation. It is worth noting that the Supragel culture system was more tolerance in terms of the initial seeding densities and less demanding, since a standard static cell culture condition was sufficient for the entire differentiation process. Our observations demonstrate a positive role of Supragel for hPSCs differentiation into islet-like cells, with additional potential in facilitating germ layer differentiation.

Cold milling is a widely used method for rehabilitating asphalt pavement, generating reclaimed asphalt pavement (RAP) chunks. Within this process, aggregates within the asphalt pavement will be crushed, forming RAP agglomerates and aggregate breakdown. However, the mechanism of these phenomena has remained unclear, and a unified evaluation method has yet to be established. In this study, RAP agglomeration and aggregate fragmentation were characterized, five distinct methods were systematically assessed, and the mechanism of RAP agglomeration and breakdown was analyzed by discrete element method (DEM) simulation based on setting different particle contact parameters, then followed by a mechanical analysis, and demonstrated in engineering. The results revealed that both agglomeration and aggregate breakdown occur within RAP particles of various sizes, with the five methods showing similar trends in quantifying these effects. Through DEM simulations and mechanical analyses, the aggregate breakdown predominantly occurs at the cutter's motion trajectory of the cutter and during crack propagation, while agglomeration was mainly related to the sliding surface's area. The milling speed and depth positively impact RAP agglomeration, while negatively affecting aggregate breakdown, and milling drum speed exerts minimal influence on these phenomena. RAP agglomeration varies considerably in different engineering projects, and cold milling parameters should be determined based on the material composition of the asphalt pavement and design requirements to control agglomeration and breakdown rates of RAP.

Abstract Hepatocellular carcinoma (HCC) is the most common malignancy in the liver, with a poor prognosis. Transmembrane protein 209 (TMEM209) involves multiple biological processes, such as substance transportation and signal transduction, and is abundantly expressed in tumor tissues. However, the relationship between TMEM209 and HCC has not been comprehensively elucidated. In this study, we aimed to illustrate this issue by in vitro and in vivo experiments. Bioinformatic analysis and clinical sample validation revealed that TMEM209 was upregulated in HCC and correlated with reduced survival duration. Functionally, TMEM209 promoted the proliferation, migration, invasion, and EMT of HCC cells in vitro and facilitated tumor growth and metastasis in xenograft models. Mechanistically, TMEM209 promoted the proliferation and metastasis of HCC in a KPNB1-dependent manner. Specifically, TMEM209 could bind to KPNB1, thereby competitively blocking the interaction between KPNB1 and the E3 ubiquitin ligase RING finger and CHY zinc finger domain-containing protein 1 (RCHY1) and preventing K48-associated ubiquitination degradation of KPNB1. Ultimately, the Wnt/β-catenin signaling pathway was activated, contributing to the progression of the malignant phenotype of HCC. In conclusion, the molecular mechanism underlying the TMEM209/KPNB1/Wnt/β-catenin axis in HCC progression was elucidated. TMEM209 is a potential biomarker and therapeutic target for HCC.

Abstract Objective Early identification of modifiable risk factors is crucial for the prevention of constipation. This study systematically investigated the relationship between genetically predicted modifiable risk factors and constipation. Methods The inverse variance weighting (IVW) method was employed as the primary analytical approach. For similar exposure indicators, the multivariate Mendelian randomization (MVMR) method was used to adjust for potential biases in univariate MR analysis. The robustness of the results was further evaluated using the MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis. Bonferroni correction was applied to reduce the false positive rate in the results. Results The IVW analysis indicated a significant causal association between genetically predicted gastroesophageal reflux disease [OR (95% CI) = 1.192 (1.079–1.315), P = 0.0005], atorvastatin use [OR (95% CI) = 16.995 (3.327–86.816), P = 0.0007], and constipation. Additionally, there was a potential causal association between education level [OR (95% CI) = 0.859 (0.767–0.964), P = 0.009], major depressive disorder [OR (95% CI) = 1.206 (1.041–1.399), P = 0.013], hypothyroidism [OR (95% CI) = 2.299 (1.327–3.985), P = 0.003], and aspirin use [OR (95% CI) = 4.872 (1.174–20.221), P = 0.029] with constipation. No causal associations were found for the other included indicators. Sensitivity analysis demonstrated the absence of evidence for heterogeneity and pleiotropy in any positive results. Conclusion This study identified several risk factors that could be targeted for the prevention of constipation, offering valuable insights for public health policies.

Abstract Background Extracting the premolars is an effective strategy for patients with bimaxillary dentoalveolar protrusion. Clear aligners (CAs) close the extraction spaces through shortening the length of aligners. The contraction force generated by the terminal of aligners makes the posterior teeth tip mesially, which is known as the roller coaster effect. This phenomenon is even worse in the 2nd premolar extraction cases. Posterior anchorage preparation is commonly used to protect the angulation of molars, taking the form of presetting distal tipping value. However, the distal tipping design aggravates the anchorage loss of anterior teeth simultaneously. This study aimed to explore the different anchorage loss of the posterior teeth when the 1st or 2nd premolars were extracted using CAs, respectively in maxillary and mandibular arches, further providing guidance for anchorage preparation design in clinical practice. Methods Two bimaxillary finite element models with different extraction patterns were established to simulate the anterior en-masse retraction process of the CAs. In Model 1, the maxillary and mandibular 1st premolars were extracted, while in Model 2, the 2nd premolars were extracted. Finite element analysis methods were utilized to analyze the tipping angle of the anterior and posterior teeth. Results Compared between two models, the anterior teeth exhibited a greater lingual inclination tendency and the posterior teeth exhibited a slighter mesial tipping tendency in Model 1 regarding individual tooth. The closer to the extraction spaces, the greater the tip, and the distal tipping tendency of the 1st premolars was more evident than the mesial tipping tendency of the 1st molars in Model 2. Compared between the maxillary and mandibular arches, the mesial tipping tendency of individual posterior tooth was more evident in the maxilla. In addition, the highest hydrostatic stress of the periodontal ligaments was concentrated on the cervical and apical parts directly adjacent to the extraction spaces, and it exhibited relatively uniform distribution in Model 1. Conclusions The individual posterior tooth showed the same mesial tipping direction but to different degree when the 1st or the 2nd premolars were extracted during clear aligner treatment. Presetting anchorage preparation design for the posterior teeth is essential to alleviate the roller coaster effect, especially in the 2nd premolar extraction cases. Furthermore, larger anchorage preparation value should be proposed for the maxillary posterior teeth.

Abstract Wearable thermoelectric generators provide a reliable power generation method for self-powered wearable electronic devices. However, there has been a lack of research regarding the comfort of wearable thermoelectric generators. Here we propose a design for a comfortable wearable thermoelectric generators system with high output power based on sandwiched thermoelectric model. This model paves the way for simultaneously optimizing comfort (skin temperature and pressure perception) and output power by systematically considering a variety of thermal resistive environments and bending states, the properties of the thermoelectric and encapsulation materials, and the device structure. To verify this strategy, we fabricate wearable thermoelectric generators using Mg-based thermoelectric materials. These materials have great potential for replacing traditional Bi2Te3-based materials and enable our wearable thermoelectric generators with a power density of 18.4 μWcm−2 under a wearing pressure of 0.8 kPa and with a skin temperature of 33 °C, ensuring the wearer’s comfort.

Abstract Background Postoperative wound infections (PWIs) significantly impact patient outcomes following open reduction and internal fixation (ORIF) of rib fractures. Identifying and understanding risk factors associated with these infections are crucial for improving surgical outcomes and patient care. Methods This retrospective study, conducted from January 2020 to October 2023 at our institution, aimed to analyze the risk factors for PWIs in patients undergoing ORIF for rib fractures. A total of 150 patients were included, with 50 in the infected group and 100 in the non-infected control group, matched for demographic and clinical characteristics. Data on variables such as intraoperative blood loss, hospital stay duration, body mass index (BMI), operation time, presence of anemia, drainage time, diabetes mellitus status, smoking habits, and age were collected. Statistical analysis involved univariate and multivariate logistic regression using SPSS software (Version 27.0), with p-values

Abstract Background N6-methyladenosine (m6A) and 5-methylcytosine (m5C) play a role in modifying long non-coding RNAs (lncRNAs) implicated in tumorigenesis and progression. This study was performed to evaluate prognostic value of m6A- and m5C-related lncRNAs and develop an efficient model for prognosis prediction in cervical cancer (CC). Methods Using gene expression data of TCGA set, we identified m6A- and m5C-related lncRNAs. Consensus Clustering Analysis was performed for samples subtyping based on survival-related lncRNAs, followed by analyzing tumor infiltrating immune cells (TIICs). Optimal signature lncRNAs were obtained using lasso Cox regression analysis for constructing a prognostic model and a nomogram to predict prognosis. Results We built a co-expression network of 23 m6A-related genes, 15 m5C-related genes, and 62 lncRNAs. Based on 9 m6A- and m5C-related lncRNAs significantly associated with overall survival (OS) time, two molecular subtypes were obtained, which had significantly different OS time and fractions of TIICs. A prognostic model based on six m6A- and m5C-related signature lncRNAs was constructed, which could dichotomize patients into two risk subgroups with significantly different OS time. Prognostic power of the model was successfully validated in an independent dataset. We subsequently constructed a nomogram which could accurately predict survival probabilities. Drug sensitivity analysis found preferred chemotherapeutic agents for high and low-risk patients, respectively. Conclusion Our study reveals that m6A- and m5C-related lncRNAs are associated with prognosis and immune microenvironment of CC. The m6A- and m5C-related six-lncRNA signature may be a useful tool for survival stratification in CC and open new avenues for individualized therapies.

Abstract Background Periodontitis is a dental disease characterized by inflammation of periodontal tissues and loss of the periodontal ligaments and alveolar bone. Exosomes are a class of extracellular vesicles that are involved in a variety of diseases by releasing active substances. In this study, we aimed to investigate the effect and mechanism of exosomes from M2 polarized macrophages (M2-exos) on osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs). Methods M2-exos were isolated from IL-4-induced RAW264.7 cells (M2 macrophages) and then treated on hPDLSCs. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, measurement of osteogenic differentiation-related genes and proteins, and inflammation was evaluated by measuring the levels of inflammatory factors. The mechanism of M2-exo was confirmed through qPCR, western blot, ALP and ARS staining. Results Results suggested that M2-exo improved osteogenic differentiation and inhibited inflammation in LPS-induced hPDLSCs. CXCL12 expression was elevated in M2 macrophages, but decreased in LPS-induced hPDLSCs. Moreover, the effect of M2-exo on osteogenic differentiation and inflammation in LPS-induced hPDLSCs was reversed by CXCL12 knockdown. Conclusion We demonstrated that M2-exo facilitated osteogenic differentiation and suppressed inflammation in LPS-induced hPDLSCs through promotion of CXCL12 expression. These results suggested the potential of M2-exo in the treatment of periodontitis, which may provide a new theoretical basis for M2-exo treatment of periodontitis.

Alzheimer’s disease is a debilitating, progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins, including amyloid plaques and intracellular tau tangles, primarily within the brain. Lysosomes, crucial intracellular organelles responsible for protein degradation, play a key role in maintaining cellular homeostasis. Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease. Currently, the efficacy of drugs in treating Alzheimer’s disease is limited, with major challenges in drug delivery efficiency and targeting. Recently, nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties. This review aims to provide a comprehensive overview of recent advances in using nanomaterials (polymeric nanomaterials, nanoemulsions, and carbon-based nanomaterials) to enhance lysosomal function in treating Alzheimer’s disease. This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function. In conclusion, this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease. The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

The latest review published in Nature Reviews Drug Discovery by Michael W. Mullowney and co-authors focuses on the use of artificial intelligence techniques, specifically machine learning, in natural product drug discovery. The authors discussed various applications of AI in this field, such as genome and metabolome mining, structural characterization of natural products, and predicting targets and biological activities of these compounds. They also highlighted the challenges associated with creating and managing large datasets for training algorithms, as well as strategies to address these obstacles. Additionally, the authors examine common pitfalls in algorithm training and offer suggestions for avoiding them.

Dockless bicycle-sharing system substantially impacts the present docked bicycle-sharing usage in the urban transportation system. This study explores such effects using usage data of docked bicycle-sharing systems in Xi’an before and after launching the dockless bicycle-sharing system. The influence period is divided into the no-influence stage, transition stage, and stabilization stage. The hotspot analysis method is employed to identify the most influenced areas. The geographically weighted regression model is then revised to determine the response of socioeconomic factors considering the launches of the dockless bicycle-sharing system. The results reveal that the critical impact of the dockless bicycle-sharing system on the docked system. Specifically, the weekly usage share of docked bicycle-sharing declined ranged from 0.51 % to 41.4 % in transition stage. Furthermore, population density, job density, per capita income, and per capita GDP are identified as the key contributing factors based on spatial analysis, where for each 1 % increase in the four indicators, docked bicycle-sharing system’s usage decreases by 1.014 %, 1.182 %, 2.021 %, and 0.904 %, respectively.

Abstract Objective The relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM). Methods T2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves. Results The prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p

Abstract The diagnosis of neurodegenerative diseases (NDDs) remains challenging, and existing therapeutic approaches demonstrate little efficacy. NDD drug delivery can be achieved through the utilization of nanostructures, hence enabling multimodal NDD theranostics. Nevertheless, both biomembrane and non-biomembrane nanostructures possess intrinsic shortcomings that must be addressed by hybridization to create novel nanostructures with versatile applications in NDD theranostics. Hybrid nanostructures display improved biocompatibility, inherent targeting capabilities, intelligent responsiveness, and controlled drug release. This paper provides a concise overview of the latest developments in hybrid nanostructures for NDD theranostics and emphasizes various engineering methodologies for the integration of diverse nanostructures, including liposomes, exosomes, cell membranes, and non-biomembrane nanostructures such as polymers, metals, and hydrogels. The use of a combination technique can significantly augment the precision, intelligence, and efficacy of hybrid nanostructures, therefore functioning as a more robust theranostic approach for NDDs. This paper also addresses the issues that arise in the therapeutic translation of hybrid nanostructures and explores potential future prospects in this field.

Abstract To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT–qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice.

Abstract Background Metabolic syndrome (MetS) is highly prevalent in individuals with schizophrenia (SZ), leading to negative consequences like premature mortality. Gut dysbiosis, which refers to an imbalance of the microbiota, and chronic inflammation are associated with both SZ and MetS. However, the relationship between gut dysbiosis, host immunological dysfunction, and SZ comorbid with MetS (SZ-MetS) remains unclear. This study aims to explore alterations in gut microbiota and their correlation with immune dysfunction in SZ-MetS, offering new insights into its pathogenesis. Methods and results We enrolled 114 Chinese patients with SZ-MetS and 111 age-matched healthy controls from Zhejiang, China, to investigate fecal microbiota using Illumina MiSeq sequencing targeting 16 S rRNA gene V3-V4 hypervariable regions. Host immune responses were assessed using the Bio-Plex Pro Human Cytokine 27-Plex Assay to examine cytokine profiles. In SZ-MetS, we observed decreased bacterial α-diversity and significant differences in β-diversity. LEfSe analysis identified enriched acetate-producing genera (Megamonas and Lactobacillus), and decreased butyrate-producing bacteria (Subdoligranulum, and Faecalibacterium) in SZ-MetS. These altered genera correlated with body mass index, the severity of symptoms (as measured by the Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms), and triglyceride levels. Altered bacterial metabolic pathways related to lipopolysaccharide biosynthesis, lipid metabolism, and various amino acid metabolism were also found. Additionally, SZ-MetS exhibited immunological dysfunction with increased pro-inflammatory cytokines, which correlated with the differential genera. Conclusion These findings suggested that gut microbiota dysbiosis and immune dysfunction play a vital role in SZ-MetS development, highlighting potential therapeutic approaches targeting the gut microbiota. While these therapies show promise, further mechanistic studies are needed to fully understand their efficacy and safety before clinical implementation.

Abstract As the important factors in coronary artery thrombosis, endothelial injury and M1 macrophage polarization are closely related to the expression of miR-34a-5p. Exosomes in plasma are mainly derived from platelets and play an important role in thrombosis. Based on these facts, this study was conducted to investigate the acting mechanism of platelet-derived exosomes (PLT-exo) in the effects of endothelial injury and M1 macrophage polarization on coronary artery thrombosis. Firstly, rats were divided into the sham-operated group and the coronary microembolization (CME) group, and their plasma-derived exosomes were extracted to detect the expression of miR-34a-5p. Next, the PLT-exo were extracted from healthy volunteers and then co-cultured with ox-LDL-induced endothelial cells and LPS-induced macrophages, respectively. Subsequently, the expression of IL-1β, IL-6, TNF-α, and ICAM-1 in endothelial cells was measured, and the level of markers related to M1 macrophage polarization and Sirt1/NF-κB pathway was detected. Finally, the above indicators were examined again after PLT-exo combined with miR-34a-5p mimic were co-cultured with endothelial cells and macrophages, respectively. The results demonstrated that the expression of miR-34a-5p in the CME group was up-regulated compared with the sham-operated group. In cell experiments, PLT-exo modulated the Sirt1/NF-κB pathway by inhibiting the expression of intracellular miR-34a-5p and down-regulated the expression of IL-1β, IL-6, TNF-α, and ICAM-1 in endothelial cells and M1 macrophage polarization. After the transfection with miR-34a-5p mimic, endothelial cell inflammatory injury and M1 macrophage polarization increased to varying degrees. In conclusion, PLT-exo can alleviate coronary artery thrombosis by reducing endothelial cell inflammation and M1 macrophage polarization via inhibiting miR-34a-5p expression. In contrast, miR-34a-5p overexpression in PLT-exo may exacerbate these pathological injuries in coronary artery thrombosis.

Abstract Humans categorize body parts, reflecting our knowledge about bodies, and this could be useful in higher-level activities involving bodies. We tested whether humans’ closest living relatives—chimpanzees—have the same ability using touchscreen tasks, focusing on the major parts: heads, torsos, arms, and legs. Six chimpanzees were trained to perform a body part matching-to-sample task using sets of pictures of chimpanzee bodies, where in each trial, the sample and choice pictures were the same. Five passed the training and received the test sessions, where three trial types were mixed: trained same-individual picture pairs; novel same-individual picture pairs; and novel different-individual picture pairs. All participants performed better than the chance level in all conditions and for all body parts. Further analyses showed differences in performance when the samples were different body parts. For example, the results revealed better performances for heads and torsos than arms and legs in “novel different-individual pairs”. The study showed that chimpanzees can visually match and categorize body parts in this experiment setting, even across different chimpanzees’ bodies, suggesting potential biological understanding. Different performances for body parts suggested a deviated categorization from humans. We hope this study will inspire future research on the evolution of body perception.

Abstract Aims Vitiligo is a chronic dermatological condition characterized by the progressive loss of melanocytes, for which traditional therapy has shown limited efficacy. This study aimed to establish a vitiligo model with easy operability, high repeatability, and stable depigmentation to provide a foundation for studying the pathogenesis and developing novel therapies for vitiligo. Methods (1) Establishing vitiligo model: Firstly, deliver B16F10 cells to the back skin of C57BL/6 J via intradermal injection (day 0), and the CD4 depletion antibody was injected intraperitoneally on day 4 and 10. Secondly, the melanoma was surgically removed on day 12. Thirdly, CD8 antibody was administered intraperitoneally every fourth day till day 30. (2) Identification of vitiligo model: H&E staining, immunohistochemistry, and immunofluorescence were used to detect the melanocytes. The melanin was detected by transmission electron microscopy (TEM), Lillie ferrous sulfate staining and L-DOPA staining. Results (1) The back skin and hair began to appear white on day 30. Melanin loss reached peak on day 60; (2) Hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence results showed melanocytes were reduced. L-DOPA staining, Lillie ferrous sulfate staining and TEM results showed that melanin decreased in the epidermis. Conclusion We successfully establishment a vitiligo mouse model which can be more capable to simulate the pathogenesis of human vitiligo and provide an important basis for the study of pathogenesis and therapy of vitiligo.

Abstract Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/− HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Helicobacter pylori (H. pylori) infection remains the leading cause of gastric adenocarcinoma, and its eradication primarily relies on the prolonged and intensive use of two antibiotics. However, antibiotic resistance has become a compelling health issue, leading to H. pylori eradication treatment failure worldwide. Additionally, the powerlessness of antibiotics against biofilms, as well as intracellular H. pylori and the long-term damage of antibiotics to the intestinal microbiota, have also created an urgent demand for antibiotic-free approaches. Herein, we describe an antibiotic-free, multifunctional copper-organic framework (HKUST-1) platform encased in a lipid layer comprising phosphatidic acid (PA), rhamnolipid (RHL), and cholesterol (CHOL), enveloped in chitosan (CS), and loaded in an ascorbyl palmitate (AP) hydrogel: AP@CS@Lip@HKUST-1. This platform targets inflammatory sites where H. pylori aggregates through electrostatic attraction. Then, hydrolysis by matrix metalloproteinases (MMPs) releases CS-encased nanoparticles, disrupting bacterial urease activity and membrane integrity. Additionally, RHL disperses biofilms, while PA promotes lysosomal acidification and activates host autophagy, enabling clearance of intracellular H. pylori. Furthermore, AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu2+ release while preserving the intestinal microbiota. Collectively, this platform presents an advanced therapeutic strategy for eradicating persistent H. pylori infection without inducing drug resistance.

Recent trends in road engineering have explored the potential of incorporating recycled solid wastes into infrastructures that including pavements, bridges, tunnels, and accessory structures. The utilization of solid wastes is expected to offer sustainable solutions to waste recycling while enhancing the performance of roads. This review provides an extensive analysis of the recycling of three main types of solid wastes for road engineering purposes: industrial solid waste, infrastructure solid waste, and municipal life solid waste. Industrial solid wastes suitable for road engineering generally include coal gangue, fly ash, blast furnace slag, silica fume, and steel slag, etc. Infrastructure solid wastes recycled in road engineering primarily consist of construction & demolition waste, reclaimed asphalt pavements, and recycled cement concrete. Furthermore, recent exploration has extended to the utilization of municipal life solid wastes, such as incinerated bottom ash, glass waste, electronics waste, plastic waste, and rubber waste in road engineering applications. These recycled solid wastes are categorized into solid waste aggregates, solid waste cements, and solid waste fillers, each playing distinct roles in road infrastructure. Roles of solid waste acting aggregates, cements, and fillers in road infrastructures were fully investigated, including their pozzolanic properties, integration effects to virgin materials, modification or enhancement solutions, engineering performances. Utilization of these materials not only addresses the challenge of waste management but also offers environmental benefits aiming carbon neutral and contributes to sustainable infrastructure development. However, challenges such as variability in material properties, environmental impact mitigation, secondary pollution to environment by leaching, and concerns regarding long-term performance need to be further addressed. Despite these challenges, the recycled solid wastes hold immense potential in revolutionizing road construction practices and fostering environmental stewardship. This review delves into a bird’s-eye view of the utilization of recycled solid wastes in road engineering, highlighting advances, benefits, challenges, and future prospects.

Abstract Objective To explore the risk factors for maternal near-miss (MNM) using the WHO near-miss approach. Methods Data were obtained from the Maternal Near-Miss Surveillance System in Hunan Province, China, 2012–2022. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (aORs) were used to identify risk factors for MNM. Results Our study included 780,359 women with 731,185 live births, a total of 2461 (0.32%) MNMs, 777,846 (99.68%) non-MNMs, and 52 (0.006%) maternal deaths were identified. The MNM ratio was 3.37‰ (95%CI: 3.23–3.50). Coagulation/hematological dysfunction was the most common cause of MNM (75.66%). Results of multivariate logistic regression analysis showed risk factors for MNM: maternal age > = 30 years old (aOR > 1, P = 2 (aOR > 1, P = 3 (aOR = 1.95, 95%CI: 1.50–2.55), prenatal examinations = 2 (aOR = 2.48, 95%CI: 1.99–3.09). Conclusion The MNM ratio was relatively low in Hunan Province. Advanced maternal age, unmarried status, a high number of pregnancies, nulliparity or high parity, a low number of prenatal examinations, and cesarean sections were risk factors for MNM. Our study is essential for improving the quality of maternal health care and preventing MNM.

Antibiotic contamination is a global environmental problem. The emerging contaminant norfloxacin (NOR) may increase the risk of drug resistance and thereby harm human health. The practical application of metal–organic framework crystals is usually limited by their powder form and difficulty in recovery. In this study, a magnetic Co-MPS-800 composite was prepared from carbonization with ZIF-67@pine sawdust, and significantly raised the NOR removing ability from wastewater. The changes in functional group composition, elemental contents, morphology, thermal stability and adsorption mechanism of the magnetic Co-MPS-800 composite were interpreted using FT-IR, XRD, SEM, BET, TGA and XPS. The Co-MPS-800 has an isoelectric point of 9.15 and a large specific surface area (174.58 m2·g−1). The impacts of pH, contact time, temperature and dosage on the performance of Co-MPS-800 were also studied. The adsorption capacity over NOR reached 221.98 mg·g−1 at 303 K, pH=6.0. The NOR adsorption is best suited a pseudo-2nd-order kinetic model and the Freundlich isotherm. Co-MPS-800 also had excellent reusability, and the removal rate reached 82.94 % after four repeated uses. Therefore, the magnetic Co-MPS-800 composite is effective in removing NOR from aqueous solutions. Altogether, this functional MOF-derived porous carbon may serve as a promising pollutant biosorbent, and its preparation strategy may provide insights for future studies.

Past research on subjective well-being (SWB) in Western society and China has revealed various contributing factors. This study conducted a series of interviews with Chinese urban residents to systematically analyze those factors based on Bronfenbrenner’s Ecological System Theory. The results revealed that 5 layers, 23 factors, and 55 elements, many of which had distinct Chinese characteristics, contributed to Chinese urban residents’ SWB. The Top Model of SWB, visualized as a spinning top or gyroscope, showcased the interdependent layers of factors impacting Chinese urban residents’ SWB. At its vertical axis is a time dimension as residents often reflect on factors by comparing their present situation with the past and the future. Discussion regarding each layer, the primary factors that comprise each layer, links between the layers, and the impact of a time dimension was included to substantiate the proposed model. The discussions focus on the study’s contribution to SWB literature, public policy-making, and future research on urban Chinese residents’ SWB.

Pancreatic metastasis is a rare malignant tumor; when it comes to multiple cancers, it may be a challenge to identify the primary lesion of new pancreatic metastases. With the continuous advancement of imaging technology, the PET/computed tomography (CT) has been widely used because of its high diagnostic accuracy and non-invasiveness. However, in the present case, the patient had history of limited small-cell lung carcinoma and prostatic cancer; the combined application of the three kinds of PET/CT was used to identify the new metastases of pancreatic and bone metastases, which suggested a high probability of primary G2 pancreatic neuroendocrine tumor with bone metastases. After the needle biopsy, samples were confirmed by diagnostic pathology as small-cell lung cancer metastasizing to the pancreas and bone. The results of our case suggests the irreplaceability of pathology and possibility of misdiagnosis by PET/CT; moreover, it also supplements clinical data for second primary cancers after small-cell lung cancer.

Abstract Diabetes often induces bone loss and the dysregulation of gut microbiota (GM) is an important cause. Punicalagin (PU) was reported to regulate GM. Therefore, we hypothesized that PU could alleviate diabetes‐induced bone loss through GM and their metabolites. In this study, high‐fat diet‐induced diabetic mice showed bone erosion and poor biomechanical properties, while PU intake significantly improved the bone condition of diabetic mice. Further investigation revealed that the abundance of some beneficial bacteria, such as Akkermansia and Ruminiclostridium_9, was higher after PU intake and highly positively correlated with the concentrations of short‐chain fatty acids (SCFAs) and serum vitamin K2, respectively. In addition, these bacteria were associated with the levels of bone metabolism‐related markers such as procollagen type I N‐terminal propeptide (P1NP) and runt‐related transcription factor‐2 (Runx2). Mechanistically, PU, on the one hand, promotes the metabolism of SCFAs, thereby increasing the levels of bone synthesis markers and inhibiting the secretion of bone absorption markers. On the other hand, the higher level of vitamin K2 greatly accelerated bone mineralization and enhanced bone strength. This work provides a new perspective to explore the mechanism by which PU intervention alleviates diabetes‐induced bone loss by regulating the GM and their metabolic products.

ObjectivesThe aim of this study is to assess the risk factors associated with thrombotic events in obstetric antiphospholipid syndrome (OAPS) patients and to develop a predictive model specifically tailored to predict the risk of postpartum thrombosis in OAPS patients without prior thrombotic events. This research seeks to enhance clinician’s awareness regarding the postpartum care and monitoring of OAPS patients.MethodsA retrospective study was conducted at the First Affiliated Hospital of the Fourth Military Medical University including 269 consecutive inpatients diagnosed with antiphospholipid syndrome (APS) from July 1, 2008 to July 31, 2022. All participants met the 2006 Sydney APS classification criteria or the “non-criteria OAPS classification”. Out of 98 candidate clinical and laboratory parameters considered, 40 potential variables were selected for analysis based on expert opinion. The logistic regression mode with the Least Absolute Shrinkage and Selection Operator (LASSO) were used to identify optimal predictive characteristics. All samples were included in the model building and a nomogram was generated based on these characteristics. The differentiation, calibration, and clinical utility of the predictive model were evaluated using the area under the curve (AUC), calibration curve, and decision curve analysis. The model was also validated by a 1000 bootstrap tests.Results126 patients with OAPS were enrolled, and a total of 89 OAPS patients who had never experienced thrombosis were retrospectively analyzed. After 3 years follow-up, 32.58% of the patients (29/89) developed thrombosis. In order to create, LASSO logistic regression identified three optimal variables: the platelet count less than 125×109/L, more than one positive aPLs (antiphospholipid antibody), and the use of low molecular weight heparin (LMWH) or low dose aspirin (LDA) after delivery. A predictive model was conducted using these three predictive indicators for patients with OAPS who experience thrombosis for the first-time. This prediction model has good distinction, good calibration, and fair clinical practicality.ConclusionOur model has good predictive ability in assessing the risk of thrombosis in patients with OAPS without prior thrombotic events. This model is easy to predict, has good discriminability and calibration, and can be utilized as a routine tool for thrombus screening in OAPS patients.

Forest ecosystems, especially within biodiversity hotspots, heavily rely on the often-overlooked understory herbaceous communities (USHC) for their structural integrity and ecological functions. Because of their modest stature, these communities have garnered insufficient attention from researchers. Therefore, in this study attention is focused on USHC, which attempts to fill this research gap. To achieve this, we established 105 sample plots in 2022 within forest ecosystems situated in the biodiversity hotspot of southwest China. Our investigation unveiled a rich biodiversity tapestry, identifying 424 plant species from 108 families and 284 genera. Notable were the 217 herbaceous species identified in the understory layer, representing 67 families and 163 genera. These understory herbaceous species accounted for 51.2 % of the overall species count. Through a detailed analysis, the sample plots were categorized into eight distinct communities using a two-way indicator species analysis. These communities exhibited diverse variations in species composition, diversity, biomass, and nutrient characteristics. Notably, community I (Eucalyptus robusta Smith + Rubus corchorifolius L. f. + Alternanthera philoxeroides (Mart.) Griseb.), V (Camptotheca acuminata Decne + Rubus parkeri Hance + Iris tectorum Maxim), VIII (Platycladus orientalis (L.) Franco + Viburnum dilatatum Thunb. + Cyclosorus interruptus (Willd.) H. Ito) stood out for their exceptional species diversity and productivity. Moreover, correlation analyses highlighted the substantial impact of topographic and soil factors on USHC. Altitude, soil water content, and total carbon content emerged as the primary determinants of species diversity. Biomass demonstrated close associations with total soil carbon and nitrogen. Furthermore, the nutrient characteristics displayed significant correlations with soil nutrient contents. These findings underscore the critical importance of prioritizing USHC attention in forest conservation and management strategies within biodiversity hotspots. The implications strongly advocate for the inclusion of these communities in planning and decision-making processes, emphasizing their pivotal role in maintaining structural and functional diversity in ecosystems.

Solitary fibrous tumor of the liver (SFTL) is an exceptionally rare mesenchymal tumor, with only 117 cases reported in the literature. While most SFTs are benign, some exhibit malignant behavior, including local recurrence and metastasis. This report presents two cases of SFTL with systemic metastases, both involving prior intracranial tumors. The first case, a 52-year-old woman, discovered a liver mass incidentally during a routine physical exam. Subsequent investigations revealed potential bone metastasis, and biopsy confirmed SFT. She received two TACE procedures, anlotinib targeted therapy, and radiotherapy for the iliac bone lesion, resulting in stable disease with reduction in lesion size. The second case, a 46-year-old man, presented with multiple liver, pelvic, and lung lesions following pelvic tumor resection, with pathology confirming SFT. He was treated with long-term anlotinib therapy, CyberKnife for hepatic, lung, and pelvic lesions, and radiofrequency ablation for hepatic lesions. Postoperative recovery was uneventful, with no tumor progression on follow-up. SFTL presents with atypical clinical and imaging features, and diagnosis requires pathological and genetic confirmation. Radical resection is preferred for solitary tumors, while comprehensive treatment, including surgery and long-term follow-up, is essential for cases with recurrence or metastasis.

Pathological scars result from abnormal wound healing and represent a fibrotic process in the repair of skin injuries. Post-burn scars are prone to malignant transformation, especially when ulceration occurs, raising concerns for precancerous lesions. We report a case of a 56-year-old female with a 50-year history of a large burn scar on her left forearm. The scar developed non-healing ulceration with local pain and itching over the past three years. Treatment with hematoporphyrin photodynamic therapy (HpD-PDT) led to resolution of the ulceration, thinning of the scar tissue, and significant alleviation of pain and itching. After a five-year follow-up, there has been no recurrence of ulceration, suggesting that photodynamic therapy effectively promotes wound healing in scarred tissue with ulcerations.

The physical microenvironment, including substrate rigidity and topology, impacts myoblast differentiation and myotube maturation. However, the interplay effect and physical mechanism of mechanical stimuli on myotube formation is poorly understood. In this study, we utilized elastic substrates, microcontact patterning technique, and particle image velocimetry to investigate the effect of substrate rigidity and topological constraints on myoblast behaviors. Our findings suggested the interplay of substrate stiffness and cellular confinement improved the myotube formation by inducing centripetal cellular motility. These results shed light on the impact of the topological substrate on myoblast differentiation and emphasize the critical role of asymmetrical cell motility during this process, which is highly correlated with cell movement and crowding. Our research provides insights into the intricate interplay between substrate properties, cell motility, and myotube formation during myogenesis. Understanding these mechanisms could trigger tissue engineering strategies and therapies to enhance muscle regeneration and function.

Abstract Climate change may affect the survival and reproduction of ectotherms. The toad‐headed lizard Phrynocephalus theobaldi, which holds the distinction of occupying the highest elevation among all reptile species on Earth, with an elevational range from 3600 to 5000 m, represents an ideal model for studying the adaptations to climatic changes across elevational gradients. Here, we used mechanistic and hybrid species distribution models (HSDM) together with characteristic measurements of thermal biology (CTmax, CTmin, and Tsel) to simulate and compare the distribution and activity periods of the lizard across elevations in response to climate change. NicheMapR simulations using only climate factors predicted that all populations will be negatively impacted by climate change (+3°C) by suffering a reduced distribution. However, the impact was clearly reduced in simulations that accounted for thermal physiological traits. Longer activity periods were predicted for all populations during climate change. The suitable distribution is predicted to change slightly, with an increase anticipated for both high and low elevation populations. However, the forecast indicates a more pronounced increase in suitable habitats for populations at higher elevations (>4200 m) compared to those at lower elevations (

BackgroundInhibition of indolamine-2,3-dioxygenase 1 (IDO1) has been proposed as a promising strategy for cancer immunotherapy; however, it has failed in clinical trials. Macrophages in the tumor microenvironment (TME) contribute to immune escape and serve as potential therapeutic targets. This study investigated the expression pattern of IDO1 in TME and its impact on prognosis and therapeutic response of patients with esophageal squamous cell carcinoma (ESCC).MethodsRNA sequencing data from 95 patients with ESCC from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic value of IDO1. Bioinformatics tools were used to estimate scores for stromal and immune cells in tumour tissues, abundance of eight immune cell types in TME, and sensitivity of chemotherapeutic drugs and immune checkpoint (IC) blockage. The results were validated using digitalized immunohistochemistry and multiplexed immunofluorescence in ESCC tissue samples obtained from our clinical center.ResultsTCGA and validation data suggested that high expression of IDO1 was associated with poor patient survival, and IDO1 was an independent prognostic factor. IDO1 expression positively correlated with macrophages in TME and PDCD1 within diverse IC genes. Single-cell RNA sequencing data analysis and multiplexed immunofluorescence verified the coexpression of IDO1 and PD-1 in tumor-associated macrophages (TAMs). Patients with high IDO1 expression showed increased sensitivity to various chemotherapeutic drugs, while were more likely to resist IC blockage.ConclusionThis study identifies IDO1 as an independent prognostic indicator of OS in patients with ESCC, reveals a compelling connection of IDO1, PD-1, and TAMs, and explores the sensitivity of patients with high IDO1 expression to chemotherapeutic drugs and their resistance to IC blockade. These findings open new avenues for potential targets in ESCC immunotherapy.

AimTo explore the association between Metabolic Score for Insulin Resistance (METS-IR) and the risk of cardiovascular disease (CVD) death in patients with rheumatoid arthritis (RA).MethodsThis retrospective cohort study extracted data on 1,218 RA patients from the National Health and Nutrition Examination Survey. The weighted univariate and multivariate Cox regression model was established to explore the association between METS-IR and CVD mortality. Subgroup analysis was performed in terms of age, gender, body mass index, diabetes, and CVD. Hazard ratios (HRs) and 95% confidence levels (CIs) were presented.ResultsIncreased METS-IR was associated with a significantly higher risk of CVD mortality (HR=4.59, 95%CI: 1.98-10.67), and METS-IR>2.48 was associated with higher odds of CVD mortality compared with METS-IR ≤ 2.25 (HR=3.57, 95%CI: 2.04-6.24). METS-IR was positively associated with the risk of CVD mortality (HR=3.83, 95%CI: 1.62-9.08), and METS-IR>2.48 was associated with a significantly higher risk of CVD mortality in contrast to METS-IR ≤ 2.25 (HR=3.38, 95%CI: 1.87-6.09).ConclusionIncreased METS-IR was associated with a significantly higher risk of CVD mortality in RA patients. Clinicians could consider incorporating the METS-IR score into routine assessment of the prognosis of RA patients.

BackgroundEvidence from observational studies on the association between folate and metabolic dysfunction-associated steatotic liver disease (MASLD) is conflicting.AimsThis study aimed to investigate the association between serum folate concentration and MASLD and further assess the causal relationship using Mendelian randomization (MR) analysis.MethodsTo investigate the causal relationship between serum folate and MASLD, we conducted a cross-sectional study that selected 1,117 participants from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). The association between serum folate level and the risk of MASLD was evaluated under a multivariate logistic regression model. In addition, we conducted a two-sample MR study using genetic data from a large genome-wide association study (GWAS) to compare serum folate level (37,465 individuals) and MASLD (primary analysis: 8,434 cases/770,180 controls; Secondary analysis:1,483 cases/17,781 controls) were performed to infer causal relationships between them. Inverse variance weighted (IVW) was used as the primary method of MR Analysis.ResultsThe results from the NHANES database showed that Tertile 3 group (Tertile 3: ≥ 48.6 nmol/L) had a significantly lower risk (OR = 0.58, 95% CI: 0.38–0.88, p = 0.010) of MASLD than Tertile 1 group (Tertile 1: < 22.3 nmol/L) after complete adjustments. However, in the IVW of MR analysis, there was no causal relationship between serum folate level and MASLD risk in the primary analysis (OR = 0.75, 95% CI: 0.55–1.02, p = 0.065) and secondary analysis (OR = 0.83, 95% CI: 0.39–1.74, p = 0.618).ConclusionIn observational analyses, we observed an inverse association between higher serum folate concentrations and a reduced risk of MASLD. Our MR study generated similar results, but the association failed to reach the significance threshold of p

Abstract Traditional atmospheric chemistry posits that sulfur dioxide (SO2) can be oxidized to sulfate (SO4 2–) through aqueous-phase reactions in clouds and gas-phase oxidation. Despite adequate knowledge of traditional mechanisms, several studies have highlighted the potential for SO2 oxidation within aerosol water. Given the widespread presence of tropospheric aerosols, SO4 2− production through aqueous-phase oxidation in aerosol water could have a pervasive global impact. Here, we quantify the potential contributions of aerosol aqueous pathways to global sulfate formation based on the GEOS-Chem simulations and subsequent theoretical calculations. Hydrogen peroxide (H2O2) oxidation significantly influences continental regions both horizontally and vertically. Over the past two decades, shifts in the formation pathways within typical cities reveal an intriguing trend: despite reductions in SO2 emissions, the increased atmospheric oxidation capacities, like rising H2O2 levels, prevent a steady decline in SO4 2− concentrations. Abating oxidants would facilitate the benefit of SO2 reduction and the positive feedback in sulfate mitigation.

Abstract In order to increase the precision and effectiveness of power system analysis and fault diagnosis, this study aims to assess the power systems in the energy sector while utilizing artificial intelligence (AI) and environmental social governance (ESG). First, the ESG framework is presented in this study to fully account for the effects of the power system on the environment, society, and governance. Second, to coordinate the operation of various components and guarantee the balance and security of the power system, the CNN-BiLSTM power load demand forecasting model is built by merging convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM). Lastly, the particle swarm optimization (PSO) algorithm is used to introduce and optimize the deep belief network (DBN), and a power grid fault diagnostic model is implemented using the PSO technique and DBN. The model’s performance is assessed through experimentation. The outcomes demonstrate how the CNN-BiLSTM algorithm significantly increases forecasting accuracy while overcoming the drawback of just having one dimension of power load data. The values of 0.054, 0.076, and 0.102, respectively, are the root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE). Effective processing of large-scale nonlinear data is achieved in the area of power grid fault diagnosis, resulting in prediction accuracy of 96.22% and prediction time of only 129.94 s. This is clearly better than other algorithms and increases fault prediction efficiency and accuracy. Consequently, the model presented in this study not only produces impressive results in fault diagnosis and load demand forecasting, but also advances the field of power system analysis in the energy industry and offers a significant amount of support for the sustainable and intelligent growth of the energy industry.

Abstract To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16–13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.

Abstract The coronavirus disease 2019 (COVID-19) remains serious around the world and causes huge deaths and economic losses. Understanding the transmission dynamics of diseases and providing effective control strategies play important roles in the prevention of epidemic diseases. In this paper, to investigate the effect of delays on the transmission of COVID-19, we propose a delayed SEIR model to describe COVID-19 virus transmission, where two delays indicating the incubation and recovery periods are introduced. For this system, we prove its solutions are nonnegative and ultimately bounded with the nonnegative initial conditions. Furthermore, we calculate the disease-free and endemic equilibrium points and analyze the asymptotical stability and the existence of Hopf bifurcations at these equilibrium points. Then, by taking the weighted sum of the opposite number of recovered individuals at the terminal time, the number of exposed and infected individuals during the time horizon, and the system cost of control measures as the cost function, we present a delay optimal control problem, where two controls represent the social contact and the pharmaceutical intervention. Necessary optimality conditions of this optimal control problem are exploited to characterize the optimal control strategies. Finally, numerical simulations are performed to verify the theoretical analysis of the stability and Hopf bifurcations at the equilibrium points and to illustrate the effectiveness of the obtained optimal strategies in controlling the COVID-19 epidemic.

Skin microbiota plays an important role in wound healing, but skin injuries are highly susceptible to wound infections, leading to disruption of the skin microbiota. However, conventional antibacterial hydrogels eliminate both probiotics and pathogenic bacteria, disrupting the balance of the skin microbiota. Therefore, it is important to develop a wound dressing that can fend off foreign pathogenic bacteria while preserving skin microbiota stability. Inspired by live bacteria therapy, we designed a probiotic hydrogel (HAEPS@L.sei gel) with high viability for promoting wound healing. Lactobacillus paracasei TYM202 encapsulated in the hydrogel has the activity of promoting wound healing, and the hydrogel matrix EPS-M76 has the prebiotic activity that promotes the proliferation and metabolism of Lactobacillus paracasei TYM202. During the wound healing process, HAEPS@L.sei gel releases lactic acid and acetic acid to resist the growth of pathogenic bacteria while maintaining Firmicutes and Proteobacteria balance at the phylum level, thus preserving skin microbiota stability. Our results showed that live probiotic hydrogels reduce the incidence of inflammation during wound healing while promoting angiogenesis and increasing collagen deposition. This study provides new ideas for developing wound dressings predicated on live bacterial hydrogels.

Segmental bone defects, stemming from trauma, infection, and tumors, pose formidable clinical challenges. Traditional bone repair materials, such as autologous and allogeneic bone grafts, grapple with limitations including source scarcity and immune rejection risks. The advent of nucleic acid nanotechnology, particularly the use of DNA hydrogels in tissue engineering, presents a promising solution, attributed to their biocompatibility, biodegradability, and programmability. However, these hydrogels, typically hindered by high gelation temperatures (∼46 °C) and high construction costs, limit cell encapsulation and broader application. Our research introduces a novel polymer-modified DNA hydrogel, developed using nucleic acid nanotechnology, which gels at a more biocompatible temperature of 37 °C and is cost-effective. This hydrogel then incorporates tetrahedral Framework Nucleic Acid (tFNA) to enhance osteogenic mineralization. Furthermore, considering the modifiability of tFNA, we modified its chains with Aptamer02 (Apt02), an aptamer known to foster angiogenesis. This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs), with cell sequencing confirming their targeting efficacy, respectively. In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation. This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction, marking a significant advancement in tissue engineering and regenerative medicine.

Cork taint has devastating effects on the aroma and quality of the wine, which can cause an annual loss of may be up to more than one billion dollars. There are many causes of cork taint, but 2,4,6-trichloroanisole (2,4,6-TCA) is a major contributor, giving the wine a wet-moldy smell. This study provided a comprehensive overview of the occurrence, detection, and control/remediation of 2,4,6-TCA. The occurrence and formation mechanisms of 2,4,6-TCA mainly include microbial O-methylation of chlorophenols and chlorination of anisole. The source of 2,4,6-TCA in wine is the cork or other woodworks, but it is also possible to contaminate wine from the environment. Due to the extremely low odor threshold concentration of 2,4,6-TCA, the effective sample pre-enrichment for instrument identification and quantification is more important. The control/remediation strategies of 2,4,6-TCA mainly include eliminating 2,4,6-TCA in cork and removing 2,4,6-TCA from wine by adsorption. Finally, the challenges and possible future research directions in this research field were discussed and proposed.

Abstract Protein biomarkers (e.g. thrombin) are of great significance for the biological process of the organism, and its aberrant expression is closely associated with the development of diseases. With thrombin, a serine protease that plays a crucial role in maintaining homeostasis and promoting blood clotting, as detection target, this study introduces a novel approach for sensitive and accurate measurement of protein biomarker expression by utilization of cyclic reverse transcription (CRT) in combination with the self-priming hairpin-triggered CRISPR-Cas12a system. In this method, an elegantly designed sensing probe is utilized to specifically bind with the thrombin protein and convert the protein signals to nucleic acids signals, following by the CRT and CRISPR-Cas12a system-based signal amplification strategy. Taking the merit of the two-stage amplification, this assay has the capability to detect thrombin at the fM level. In addition, due to the aptamer sequence’s strong selectivity to thrombin protein and the dual-check process in the signal amplification process (first in the CRT and second in the CRISPR system), the proposed test demonstrates exceptional specificity in detecting thrombin. By re-designing the sensing probe, the established method could be extended to various protein biomarker detection. Ultimately, this assay has successfully enabled the accurate evaluation of biomarker levels in constructed clinical samples, showing significant potential for application in the realm of clinical molecular diagnosis.

To enrich the research methods for studying the development law of bed separation, this paper takes the upper 08 working face of 221 in Shilawusu Mine as the research object, and comprehensively determines the location of bed separation through distributed optical fiber (BOTDR) and fixed-point optical fiber. The particle flow code (PFC2D) is used to study the pattern of the separation layer development under the conditions of large mining height and large mining depth. The results show that, as the working face advances away from the cutting hole, the separated layer develops intermittently from the bottom to the bottom of the key layer, and the depth of separation layer development is around 440 m, 396 m, 376 m, 331 m, 321 m and 296 m, and the layer stops at the bottom of the main key layer of coarse sandstone. The overburden transport mainly goes through the stages of subsidence of the lower key layer, rapid subsidence of the upper sub-key layer, development of overburden movement towards the bottom of the main key layer of coarse sandstone, and transport of the main key layer. The separated layer position is proportional to the advancement distance of the working face, and the development of the separated layer is mainly divided into three stages, which are gestation (Ⅰ)-accelerated expansion (Ⅱ)- compression stage (Ⅲ).

Abstract Realizing precise and fast position control of the gear is a challenging issue because of its nonlinearity, parameter uncertainty and external disturbance. Therefore, this paper researches the clutch position control considering the influence because of the factor on the system performance. By virtue of the traditional adaptive control method, an improved strategy based on finite time theory is proposed to further improve the convergence rate as well as the position tracking precision. First, a model of electromechanical clutch actuator system is established by theoretical analysis. Then, an enhanced adaptive controller is designed using finite time idea by introducing power function in the virtual control. And parameter update rate is adopted in the control action. Next, the stability of the control system is proved theoretically. Finally, Matlab simulations and experimental bench test are carried out to exhibit the effectiveness of the presented method. The results show that the satisfactory performance has been achieved with accurate position tracking and fast convergence speed.

Objective The Cruise Home Port Station on Chongqing Rail Transit Line 9 is constructed from in-situ expansion of the existing interval tunnel (including a connecting passage). Due to the complex geological conditions, the initial stress field of surrounding rock, and the structure of the existing interval tunnel, analysis and research of the complex mechanical behavior of the interval tunnel during construction is essential to ensure engineering safety. Method After outlining the overview of the excavation project, a three-dimensional finite element numerical model, utilizing an anisotropic jointed rock mass elastoplastic model, is established. The model geometric features, geological characteristics, structural features, and procedural characteristics are further determined. Three measurement lines (connecting passage centerline, left-line large-mileage interval tunnel centerline, right-line small-mileage interval tunnel centerline) are selected for analyzing land subsidence above these three lines and deformation around the left-line and right-line tunnels. Simulation values are compared with measured values to study the deformation characteristics of surrounding rock and structure during the construction process of interval tunnel expansion and excavation. Result & Conclusion The comparison of model-simulated and construction-measured results indicate that the established finite element model is reasonable. The connecting passage expansion and excavation construction leads to a significant increase in convergence deformation around the tunnel, with the maximum deformation occurring at the intersection of the existing connecting passage and the construction main tunnel. Therefore, backfilling with spoil inside the connecting passage is recommended to ensure the safety and smooth implementation of tunnel excavation construction.