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Abstract Background Wood-feeding termites have been employed as sources of novel and highly efficient lignocellulolytic enzymes due to their ability to degrade lignocellulose efficiently. As a higher wood-feeding termite, Globitermes sulphureus (Blattaria: Termitidae) plays a crucial role as a decomposer in regions such as Vietnam, Singapore, Myanmar, and Yunnan, China. However, the diversity of its gut microbiome and carbohydrate-active enzymes (CAZymes) remains unexplored. Here, we analyzed the diversity of hindgut microbial communities and CAZymes in a higher wood-feeding termite, G. sulphureus, and a lower wood-feeding termite, Coptotermes formosanus (Blattaria: Rhinotermitidae). Results 16S rRNA sequencing revealed that Spirochaetota, Firmicutes, and Fibrobacterota were the dominant microbiota in the hindgut of the two termite species. At the phylum level, the relative abundances of Proteobacteria and Bacteroidota were significantly greater in the hindgut of C. formosanus than in G. sulphureus. At the genus level, the relative abundances of Candidatus_Azobacteroides and Escherichia-Shigella were significantly lower in the hindgut of G. sulphureus than in C. formosanus. Metagenomic analysis revealed that glycoside hydrolases (GHs) with cellulases and hemicellulases functions were not significantly different between G. sulphureus and C. formosanus. Interestingly, the cellulases in G. sulphureus were mainly GH5_2, GH5_4, GH6, GH9, and GH45, while the hemicellulases were mainly GH11, GH8, GH10, GH11, GH26, and GH53. In C. formosanus, the cellulases were mainly GH6 and GH9, and the hemicellulases were mainly GH5_7, GH5_21, GH10, GH12, and GH53. In addition, β-glucosidase, exo-β-1,4-glucanase, and endo-β-1,4-glucanase activities did not differ significantly between the two termite species, while xylanase activity was higher in G. sulphureus than in C. formosanus. The bacteria encoding GHs in G. sulphureus were mainly Firmicutes, Fibrobacterota, and Proteobacteria, whereas Bacteroidota and Spirochaetota were the main bacteria encoding GHs in C. formosanus. Conclusions Our findings characterized the microbial composition and differences in the hindgut microbiota of G. sulphureus and C. formosanus. Compared to C. formosanus, G. sulphureus is enriched in genes encoding for hemicellulase and debranching enzymes. It also highlights the rich diversity of GHs in the hindgut microbiota of G. sulphureus, including the GH5 subfamily, GH6, and GH48, with the GH6 and GH48 not previously reported in other higher termites. These results strengthen the understanding of the diversity of termite gut microbiota and CAZymes.

Abstract The electronic medical record management system plays a crucial role in clinical practice, optimizing the recording and management of healthcare data. To enhance the functionality of the medical record management system, this paper develops a customized schema designed for ophthalmic diseases. A multi-modal knowledge graph is constructed, which is built upon expert-reviewed and de-identified real-world ophthalmology medical data. Based on this data, we propose an auxiliary diagnostic model based on a contrastive graph attention network (CGAT-ADM), which uses the patient’s diagnostic results as anchor points and achieves auxiliary medical record diagnosis services through graph clustering. By implementing contrastive methods and feature fusion of node types, text, and numerical information in medical records, the CGAT-ADM model achieved an average precision of 0.8563 for the top 20 similar case retrievals, indicating high performance in identifying analogous diagnoses. Our research findings suggest that medical record management systems underpinned by multimodal knowledge graphs significantly enhance the development of AI services. These systems offer a range of benefits, from facilitating assisted diagnosis and addressing similar patient inquiries to delving into potential case connections and disease patterns. This comprehensive approach empowers healthcare professionals to garner deeper insights and make well-informed decisions.

Abstract Although sodium–glucose transport protein-2 (SGLT2) inhibitors (SGLT2i) do not increase the risk of acute kidney injury (AKI) in general, they may pose a risk in patients undergoing angiography. This prospective cohort study aimed to evaluate the safety and efficacy of SGLT2i for post-contrast AKI (PC-AKI) in patients with type 2 diabetes mellitus (T2DM). Following screening, 306 patients with T2DM selected to undergo coronary arterial angiography with or without percutaneous intervention were enrolled. Patients were divided into the SGLT2i exposure and non-exposure groups. The primary outcome was PC-AKI, defined as an increase in serum creatinine levels > 0.5 mg/dL (44.2 µmol/L), or 25% above the baseline, within 48–72 h after exposure to contrast medium. The incidence of PC-AKI in the overall T2DM population was 5.2% (16/306). Following 1:1 propensity score matching, the incidence of PC-AKI was significantly higher in the SGLT2i group than in the non-SGLT2i group (10.7% vs. 2.9%; P = 0.027), with an odds ratio of 4.5 (95% confidence interval: 1.0–20.2; P = 0.047). Furthermore, PC-AKI occurred at a higher rate among short-term users of SGLT2i than long-term users (20.5% vs. 3.4%, P = 0.018). Thus, our findings suggest an increased risk of PC-AKI associated with short-term SGLT2i therapy in patients with T2DM.

Abstract Artificial wrinkles, especially those with responsive erasure/regeneration behaviors have gained extensive interest due to their potential in smart applications. However, current wrinkle modulation methods primarily rely on network rearrangement, causing bottlenecks in in situ wrinkle regeneration. Herein, we report a dually cross-linked network wherein [2]rotaxane cross-link can dissipate stress within the wrinkles through its sliding motion without disrupting the network, and quadruple H-bonding cross-link comparatively highlight the advantages of [2]rotaxane modulation. Acid stimulation dissociates quadruple H-bonding and destructs network, swiftly eliminating the wrinkles. However, the regeneration process necessitates network rearrangement, making in situ recovery unfeasible. By contrast, alkaline stimulation disrupts host–guest recognition, and subsequent intramolecular motion of [2]rotaxane dissipate energy to eliminate wrinkles gradually. The always intact network allows for the in situ recovery of surface microstructures. The responsive behaviors of quadruple H-bonding and mechanical bond are orthogonal, and their combination leads to wrinkles with multiple but accurate responsiveness.

Internal curing is an effective method to reduce the autogenous shrinkage of cementitious materials. Besides, the increasing in relative humidity (RH) due to the internal curing also reduces the coefficient of thermal expansion (CTE), which is beneficial for enhancing the anti-cracking performance of cementitious materials. In this paper, effects of superabsorbent polymers (SAP) on the microstructure and performance of cementitious materials were investigated. The superabsorbent polymer (SAP) changes the time and spatial distribution of water in cementitious materials, so it should have an influence on the microstructure of cement matrix, thus affecting the performance of cementitious materials. Results indicate that the CTE of concrete increases over time, while that of concrete with SAP shows a completely different behavior. In 0.1 % SAP system, the CTE increases slowly over time after about 2days, while in 0.2 % SAP and 0.3 % SAP systems, the CTE is nearly stabilized during the test period. Low-field nuclear magnetic resonance (LF NMR) results indicate that the SAP decreases the number of empty capillary pores and increases the total porosity, which inhibits the increase of CTE over time. The dosage of SAP plays an important role in enhancing the internal curing performance. By increasing the dosage of SAP, the number of empty capillary pores decreases, the saturation degree of capillary pores rises, and consequently, the CTE and autogenous shrinkage of concrete are reduced.

The presence of antibiotics as emerging micropollutants in the aquatic environment has been raising health concerns for a number of years. Macrolides (MLs) are a large class of widely-used antibiotics, but there is a lack of information on their distribution and risks in surface waters across the central and western regions of China. To clearly describe the pollution characteristics and risks of MLs in Weihe River (the largest tributary of the Yellow River), analysis of 5 typical MLs was conducted using a newly developed LC−MS/MS method for 50 water samples collected over three seasons during 2021–2022. The results revealed that the area showed comparable ML concentrations with other regions worldwide. However, the ML concentrations were much lower than those in the river during 2016 from a previous study. Furthermore, concentrations exhibited significant seasonal variation, with highest concentrations in the winter. Along the main stream of the Weihe River, the sampling sites close to the wastewater treatment plants (WWTPs) and livestock farms exhibited higher concentrations of MLs, indicating the significant contribution from WWTPs and animal husbandry to the emission of MLs. The risk quotients (RQs) suggested that the ecological risks associated with MLs were most pronounced in winter among the three seasons, with erythromycin posing a high or medium risk to algae at all sampling sites. The results of this study will be of importance towards the goal of understanding the presence of these emerging contaminants in surface waters and any required risk reduction measures.

IntroductionPanicle number (PN) is one of the three key yield components in rice, maintaining stable tiller and PN is a crucial characteristic of an ideal plant architecture. Understanding the molecular mechanisms underlying PN is essential for breeders aiming to improve rice yield.MethodsTo dissect the genetic architecture of panicle number, a genome-wide association study (GWAS) was conducted in 411 japonica rice varieties. GWAS analysis was carried out with the mixed linear model using 743,678 high-quality SNPs.ResultsOver two experimental years, we detected a total of seven quantitative trait loci (QTLs), located on chromosomes 1, 4, 6, 8, 11, and 12; notably, qPN1.1 and qPN8 were detected consistently in both years. By combining haplotype and expression analyses, OsCKX11 was identified as the candidate gene for qPN8, while LOC_Os01g07870 and LOC_Os01g07950 were identified as candidate genes for qPN1.1. Significant differences were observed among the haplotypes of these candidate genes. Additionally, qRT-PCR results showed that LOC_Os01g07870 expression levels were significantly lower in accessions with high panicle numbers compared to those with low panicle numbers.DiscussionTo understand the natural biological function of these candidate genes, further research involving overexpression or silencing in rice is needed. Despite these challenges, our results will lay the foundation for further study of panicle development and provide valuable genetic resources for developing high-panicle-number rice cultivars using genetic engineering and molecular breeding.

Abstract Hafnium‐oxide‐based ferroelectrics have garnered considerable research interest, primarily for their robust ferroelectricity at the nanoscale and their high compatibility with complementary metal‐oxide‐semiconductors processes. However, the impact of electrodes on the ferroelectric properties of hafnium‐oxide layer, particularly that of top electrodes, is not yet fully understood even in the simplest capacitor geometry. In this study, the La0.67Sr0.33MnO3/Hf0.5Zr0.5O2 (LSMO/HZO) epitaxial heterostructure is utilized as a model system to conduct a systematic comparative study on ferroelectricity between the LSMO/HZO (H‐LS) bilayer and LSMO/HZO/LSMO (LS‐H‐LS) trilayer samples. In comparison to the H‐LS sample, the LS‐H‐LS sample exhibits a more uniform polar domain configuration and larger ferroelectric polarization. Moreover, the LS‐H‐LS sample exhibits significant improvements in leakage, endurance, and retention. These substantial enhancements in ferroelectricity are likely due to interfacial stress imposed by the LSMO capping layer and its capacity to accommodate extra oxygen vacancies. These results underscore the pivotal role of oxide‐based top electrodes in determining the ferroelectricity of hafnium‐oxide‐based heterostructures, providing crucial insights for optimizing the performance of innovative ferroelectric devices.

BackgroundMyasthenia Gravis (MG) is an autoimmune disease that causes muscle weakness in 80% of patients, most of whom test positive for anti-acetylcholine receptor (AChR) antibodies (AChR-Abs). Predicting and improving treatment outcomes are necessary due to varying responses, ranging from complete relief to minimal improvement.ObjectiveOur study aims to develop and validate an interpretable machine learning (ML) model that integrates systemic inflammation indices with traditional clinical indicators. The goal is to predict the short-term prognosis (after 6 months of treatment) of AChR-Ab+ generalized myasthenia gravis (GMG) patients to guide personalized treatment strategies.MethodsWe performed a retrospective analysis on 202 AChR-Ab+ GMG patients, dividing them into training and external validation cohorts. The primary outcome of this study was the Myasthenia Gravis Foundation of America (MGFA) post-intervention status assessed after 6 months of treatment initiation. Prognoses were classified as “unchanged or worse” for a poor outcome and “improved or better” for a good outcome. Accordingly, patients were categorized into “good outcome” or “poor outcome” groups. In the training cohort, we developed and internally validated various ML models using systemic inflammation indices, clinical indicators, or a combination of both. We then carried out external validation with the designated cohort. Additionally, we assessed the feature importance of our most effective model using the Shapley Additive Explanations (SHAP) method.ResultsIn our study of 202 patients, 28.7% (58 individuals) experienced poor outcomes after 6 months of standard therapy. We identified 11 significant predictors, encompassing both systemic inflammation indexes and clinical metrics. The extreme gradient boosting (XGBoost) model demonstrated the best performance, achieving an area under the receiver operating characteristic (ROC) curve (AUC) of 0.944. This was higher than that achieved by logistic regression (Logit) (AUC: 0.882), random forest (RF) (AUC: 0.917), support vector machines (SVM) (AUC: 0.872). Further refinement through SHAP analysis highlighted five critical determinants—two clinical indicators and three inflammation indexes—as crucial for assessing short-term prognosis in AChR-Ab+ GMG patients.ConclusionOur analysis confirms that the XGBoost model, integrating clinical indicators with systemic inflammation indexes, effectively predicts short-term prognosis in AChR-Ab+ GMG patients. This approach enhances clinical decision-making and improves patient outcomes.

Objective: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorlycontrolled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocytedamage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluatethe nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore theunderlying mechanism.Materials and Methods: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) toinduce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, andorgan weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levelswere determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the ratswere sacrificed and their renal tissues were removed for histopathological assessment.Results: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepaticweights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine(Cr) and, albumin. There was a decrease (P

Abstract Background Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes. Methods The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed. Results This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P

Abstract The signing of the Regional Comprehensive Economic Partnership agreement brings new opportunities for the development of international air transportation. Faced with fierce competition, it is worth studying how hub airports should enhance competitiveness, and how low-cost carriers and full-service carriers should optimize the RCEP international airline network layout for better development. Aiming at providing suggestions for the development of hub airports, low-cost and full-service carriers in the RCEP international airline network, this paper identifies the hub airports, analyzes the layout of the RCEP international airline network, and the multi-layered characteristics based on an improved contribution matrix using data from 2010 to 2019 collected from the Official Airline Guide (OAG). This method comprehensively considers attributes of hub airports and the multi-layered characteristics of the airports and routes. The layout analysis indicates that the RCEP international transportation market presents a more open environment for competition and cooperation where base carriers are often the biggest supporters of hub construction. The multi-layered characteristics analysis reveals that low-cost carriers contribute more towards opening up new RCEP routes than full-service carriers. It is advised that carriers newly entering the RCEP international aviation transportation market and low-cost carriers dedicate to establishing new routes around their hub airports to monopolize this market and enhance their market share, whilst full-service carriers consolidate existing routes and increase route density to achieve economic benefits.

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.

Abstract Objective Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). Methods A total of 383 patients (aged 24–76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (

Upland crop-rice cropping systems (UCR) facilitate sustainable agricultural intensification. Accurate UCR cultivation mapping is needed to ensure food security, sustainable water management, and rural revitalization. However, datasets describing cropping systems are limited in spatial coverage and crop types. Mapping UCR is more challenging than crop identification and most existing approaches rely heavily on accurate phenology calendars and representative training samples, which limits its applications over large regions. We describe a novel algorithm (RRSS) for automatic mapping of upland crop–rice cropping systems using Sentinel-1 Synthetic Aperture Radar (SAR) and Sentinel-2 Multispectral Instrument (MSI) data. One indicator, the VV backscatter range, was proposed to discriminate UCR and another two indicators were designed by coupling greenness and pigment indices to further discriminate tobacco or oilseed UCR. The RRSS algorithm was applied to South China characterized by complex smallholder rice cropping systems and diverse topographic conditions. This study developed 10-m UCR maps of a major rice bowl in South China, the Xiang-Gan-Min (XGM) region. The performance of the RRSS algorithm was validated based on 5197 ground-truth reference sites, with an overall accuracy of 91.92%. There were 7348 km2 areas of UCR, roughly one-half of them located in plains. The UCR was represented mainly by oilseed-UCR and tobacco-UCR, which contributed respectively 69% and 15% of UCR area. UCR patterns accounted for only one-tenth of rice production, which can be tripled by intensification from single rice cropping. Application to complex and fragmented subtropical regions suggested the spatiotemporal robustness of the RRSS algorithm, which could be further applied to generate 10-m UCR datasets for application at national or global scales.

Abstract Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180–365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients’ improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

In order to explore the antioxidant ability of different solvent extracts of Ge-riched Auricularia auricular mycelium in vitro, the Ge-riched A. auricular mycelium was extracted by water, 70% ethanol and ethyl acetate. The scavenging ability of different extracts on superoxide anion free radical, hydroxyl free radical and DPPH free radical were compared. The comprehensive antioxidant capacity of different solvent extracts was evaluated by subordinate function value, and the correlation between substance content and antioxidant capacity were analyzed. The results showed that the content of organic Ge in Ge-riched A. auricular mycelium was 542.83 μg/g. The extraction rate and substance content of different solvent extracts were different, the extraction rate of water extract and ethanol extract was higher, the polysaccharide content of water extract was the highest, and the polyphenol and flavonoid content of ethyl acetate extract was the highest. Different solvent extracts had certain scavenging ability on free radicals，and the extract concentration increased with the increase. Water extract had the strongest scavenging rate of superoxide anion free radical，when the extract concentration was 9 mg/mL, the highest clearance rate was 43.32%. 70% ethanol extract had the best scavenging effect on hydroxyl free radical and DPPH free radical. When the extract concentration was 9 mg/mL, the scavenging rate was 70.10% and 76.99%, respectively. Polysaccharides, polyphenols and flavonoids all played different roles in scavenging free radicals, and ethanol extract had the strongest comprehensive antioxidant capacity. The contents of polysaccharides, polyphenols and flavonoids were significant (P

Abstract Background Malnutrition is a common geriatric syndrome that is closely associated with adverse clinical outcomes and poses significant harm to older adults. Early assessment of nutritional status plays a crucial role in preventing and intervening in cases of malnutrition. However, there is currently a lack of measurable methods and biomarkers to evaluate malnutrition in older adults accurately. The aim of this study is to investigate the independent correlation between serum levels of amino acids and malnutrition in older adults, and to identify effective metabolomics biomarkers that can aid in the early detection of geriatric malnutrition. Methods A total of 254 geriatric medical examination participants from Beijing Hospital were included in the study, consisting of 182 individuals with normal nutritional status (Normal group) and 72 patients at risk of malnutrition or already malnourished (MN group). Malnutrition was assessed using the Mini-Nutritional Assessment Short-Form (MNA-SF). Demographic data were collected, and muscle-related and lipid indexes were determined. Serum amino acid concentrations were measured using isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation between serum amino acid levels and malnutrition was analyzed using non-parametric tests, partial correlation analysis, linear regression, and logistic regression. Results The geriatric MN group exhibited significantly lower serum aromatic amino acid levels (P

Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis. Objectives: To evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis. Methods: The effects of GMSCs on RA were assessed by comparing the symptoms of the K/B × N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments. Results: We found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation. Conclusion: Our results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.

The poly (lactic-co-glycolic acid) (PLGA) based nanoparticles have been applied for drug delivery due to their simple preparation, biodegradability, and ideal biocompatibility. In this study, the factors affecting the degradation of PLGA-based nanoparticles are reviewed, encompassing the ratio of PLA to PGA, relative molecular weight, crystallinity, and preparation process of PLGA nanoparticles. The drug release behavior of PLGA-based nanoparticles, such as the degradation environment, encapsulated drug properties of polymers, and drug loading rates, are also discussed. Since gastrointestinal cancer is one of the major global threats to human health, this paper comprehensively summarizes the application of PLGA nanoparticles in gastrointestinal cancers from diagnosis, chemotherapy, radiotherapy, and novel tumor treatment methods (immunotherapy, gene therapy, and photothermal therapy). Finally, the future application of PLGA-based drug delivery systems in treating gastrointestinal cancers is discussed. The bottleneck of application status and the prospect of PLGA-nanoparticles in gastrointestinal tumor application are presented. To truly realize the great and wide application of PLGA-based nanoparticles, collaborative progress in the field of nanomaterials and life sciences is needed.

Abstract Subauroral red (SAR) arcs are commonly observed ionospheric red line emissions. They are usually attributed to subauroral electron heating by inner magnetospheric heat flux (IMHF). However, the role of IMHF in changing the ionosphere‐thermosphere (IT) still remains elusive. We conduct controlled numerical experiments with the Thermosphere‐Ionosphere Electrodynamic General Circulation Model (TIEGCM). Coulomb collisional heat flux derived with the Comprehensive Inner Magnetosphere Ionosphere (CIMI) model and empirical subauroral polarization streams (SAPS) are implemented in TIEGCM. The heat flux causes electron temperature enhancement, electron density depletion, and consequently SAR arcs formed in the dusk‐to‐midnight subauroral ionosphere region. SAPS cause more substantial plasma and neutral heating and plasma density variations in a broader region. The maximum enhancement of subauroral red line emission rate is comparable to that caused by the heat flux. However, the visibility of SAR arcs also depends on the relative enhancement to the background brightness.

Purpose: Primary surgery failure of macular holes causes poor visual acuity outcomes. Several studies indicate that small-medium idiopathic full-thickness macular holes (iFTMH) have consistent and high anatomical closure rates after vitrectomy and internal limiting membrane (ILM) peeling, regardless of iFTMH diameters. However, there is no systematic analysis examining the relationship between iFTMH diameters and anatomical closure rates. Methods: In this systematic review and meta-regression, we searched PubMed, Embase, and Web of Science databases on October 24th, 2022. We included studies regarding iFTMH, with ILM peeling/inverted flap technique, long-lasting gas tamponade, and face-down position after surgery. Univariable meta-regression with a restricted cubic spline model and component-plus-residual plot after covariables adjustment were used to explore non-linear association. Results: A total of 7257 participants from 19 randomized controlled trials and 49 observational studies were included in this meta-analysis. In ILM peeling group, every 100-μm increment in diameter was associated with a 3.8 % (95 % confidence interval [CI], 1.8%–5.7 %, P 0.9). The restricted cubic spline model and component-plus-residual plot controlling for age, sex, and symptom duration prior to surgery showed no evident non-linearity in both surgical techniques. Conclusions: The iFTMH diameter is linear and inversely associated with the anatomical closure rate after the ILM peeling technique, but not with the inverted flap technique. The present study supports the use of advanced techniques, e.g., inverted flap technique, in small-medium iFTMH to improve anatomical closure rates.

Summary: Bietti crystalline dystrophy (BCD) is an autosomal recessive inherited retinal disease (IRD) and its early precise diagnosis is much challenging. This study aims to diagnose BCD and classify the clinical stage based on ultra-wide-field (UWF) color fundus photographs (CFPs) via deep learning (DL). All CFPs were labeled as BCD, retinitis pigmentosa (RP) or normal, and the BCD patients were further divided into three stages. DL models ResNeXt, Wide ResNet, and ResNeSt were developed, and model performance was evaluated using accuracy and confusion matrix. Then the diagnostic interpretability was verified by the heatmaps. The models achieved good classification results. Our study established the largest BCD database of Chinese population. We developed a quick diagnosing method for BCD and evaluated the potential efficacy of an automatic diagnosis and grading DL algorithm based on UWF fundus photography in a Chinese cohort of BCD patients.

Introduction Coronary microcirculation dysfunction (CMD) is prevalent in patients with coronary artery disease (CAD). Current therapies for CMD are focused on pharmacotherapy, non-pharmacological treatments such as enhanced external counterpulsation (EECP) have shown favourable results in patients with CAD. However, whether EECP can improve CMD remains unknown. This study is designed to evaluate the effectiveness of EECP on CMD in patients with CAD, and to assess the feasibility of conducting a multicentre randomised controlled trial.Methods and analysis This study is a single-centre, outcome-assessor-blinded, parallel randomised controlled trial. A total of 110 participants with CAD will be included and randomly assigned to either the intervention group (EECP plus optimal medical therapy (OMT)) or the control group (OMT alone). EECP will be administered by operators for 60 min, 5 times per week for 7 weeks (35 times in total). Outcomes include patients’ retention rates, the primary outcome and secondary outcomes. The primary outcome is the change in Myocardial Perfusion Reserve Index with cardiac MRI from baseline to the end of follow-up. The planned study duration is from 2024 to 2026.Ethics and dissemination Ethical approval was obtained from the Ethics Committee of the Eighth Affiliated Hospital, Sun Yat-sen University (ID: 2023-045-03). The findings will be disseminated in peer-reviewed publications.Trial registration number ChiCTR2300076231.

Not available.

Abstract Using NASA's Global‐scale Observations of the Limb and Disk (GOLD) imager, we report nightside ionospheric changes during the G5 super geomagnetic storm of 10 and 11 May 2024. Specifically, the nightside southern crest of the Equatorial Ionization Anomaly (EIA) was observed to merge with the aurora near the southern tip of South America. During the storm, the EIA southern crest was seen moving poleward as fast as 450 m/s. Furthermore, the aurora extended to mid‐latitudes reaching the southern tips of Africa and South America. The poleward shift of the equatorial ionospheric structure and equatorward motion of the aurora means there was no mid‐latitude ionosphere in this region. These observations offer unique insights into the ionospheric response to extreme geomagnetic disturbances, highlighting the complex interplay between solar activity and Earth's upper atmosphere.

Abstract Objective To investigate the recovery of binocular stereopsis recovery and its influencing factors in children with intermittent exotropia after successful correction of eye position. Methods Prospective clinical study. A total of 178 patients, aged 9 ∼ 14 (10.8 ± 1.7) years, who were successfully corrected after intermittent exotropia surgery at the Beijing Tongren Hospital Affiliated to Capital Medical University from October 2023 to September 2023 were collected, the follow-up duration was six-month or longer. Paired t test, Pearson correlation analysis and multivariable linear regression analysis were used to probe preoperative clinical features that may predict the stereopsis six months after surgery. Results Six months after surgery, the angle of deviation of the patients met the orthotopic standard, and there was significant difference compared with that before surgery (distant: -2.7△±3.2△ vs. -30.5△±8.4△, t=-25.3, P

Abstract Arising from the extreme/saddle point in electronic bands, Van Hove singularity (VHS) manifests divergent density of states (DOS) and induces various new states of matter such as unconventional superconductivity. VHS is believed to exist in one and two dimensions, but rarely found in three dimension (3D). Here, we report the discovery of 3D VHS in a topological magnet EuCd2As2 by magneto-infrared spectroscopy. External magnetic fields effectively control the exchange interaction in EuCd2As2, and shift 3D Weyl bands continuously, leading to the modification of Fermi velocity and energy dispersion. Above the critical field, the 3D VHS forms and is evidenced by the abrupt emergence of inter-band transitions, which can be quantitatively described by the minimal model of Weyl semimetals. Three additional optical transitions are further predicted theoretically and verified in magneto-near-infrared spectra. Our results pave the way to exploring VHS in 3D systems and uncovering the coordination between electronic correlation and the topological phase.

Abstract Background m6A modification is currently recognized as a major driver of RNA function that maintains cancer cell homeostasis. Long non-coding (Lnc) RNAs control cell proliferation and play an important role in the occurrence and progression of colorectal cancer (CRC). ZCCHC4 is a newly discovered m6A methyltransferase whose role and mechanism in tumors have not yet been elucidated. Methods The EpiQuik m6A RNA methylation kit was used to detect the level of total RNA m6A in six types of digestive tract tumors. The Kaplan-Meier method and receiver operating characteristic curve were used to evaluate the prognostic and diagnostic value of the newly discovered m6A methyltransferase, ZCCHC4, in CRC. The effects on CRC growth in vitro and in vivo were studied using gain- and loss-of-function experiments. The epigenetic mechanisms underlying ZCCHC4 upregulation in CRC were studied using RIP, MeRIP-seq, RNA pull-down, and animal experiments. Results We reported that the ZCCHC4-LncRNAGHRLOS-KDM5D axis regulates the growth of CRC in vitro and in vivo. We found that ZCCHC4 was upregulated in primary CRC samples and could predict adverse clinical outcomes in patients with CRC. Mechanistically, ZCCHC4 downregulated LncRNAGHRLOS to promote CRC tumorigenesis. As a downstream molecule of LncRNAGHRLOS, KDM5D directly controls CRC cell proliferation, migration, and invasion. Conclusion This study suggests that the ZCCHC4 axis contributes to the tumorigenesis and progression of CRC and that ZCCHC4 may be a potential biomarker for this malignancy.

Drought is one of the abiotic stresses limiting the production of soybean (Glycine max). Elucidation of the genetic and molecular basis of the slow-wilting (SW) trait of this crop offers the prospect of its genetic improvement. A panel of 188 accessions and a set of recombinant inbred lines produced from a cross between cultivars Liaodou 14 and Liaodou 21 were used to identify quantitative-trait loci (QTL) associated with SW. Plants were genotyped by Specific-locus amplified fragment sequencing and seedling leaf wilting was assessed under three water-stress treatments. A genome-wide association study identified 26 SW-associated single-nucleotide polymorphisms (SNPs), including three located in a 248-kb linkage-disequilibrium (LD) block on chromosome 2. Linkage mapping revealed a major-effect QTL, qSW2, associated with all three treatments and adjacent to the LD block. Fine mapping in a BC2F3 population derived from a backcross between Liaodou 21 and R26 confined qSW2 to a 60-kb interval. Gene expression and sequence variation analysis identified the gene Glyma.02 g218100, encoding an auxin transcription factor, as a candidate gene for qSW2. Our results will contribute significantly to improving drought-resistant soybean cultivars by providing genetic information and resources.

Remote sensing change detection has achieved amazing results in recent years, especially the application of convolutional neural networks (CNN) and Transformer networks, which have revolutionized the field. However, the complex ground cover changes and the differences in lighting conditions caused by different times still pose challenges to the detection accuracy. In order to further extract spatial feature information and suppress irrelevant influences, we innovatively propose an edge-enhanced and time-synchronized remote sensing change detection network, called CNN and transformer-based spatio-temporally synchronized network (CTST). CTST designs a unique feature-integrated coding model with CNN and Transformer architectures, which enhances the model's understanding of the global dependencies and the extraction effect of the local features through the dynamic weight allocation method. We designed the edge salient feature enhancement module, which uses a dual operator fusion structure to combine the edge semantic information with the depth feature information, greatly enhancing the model's ability to recognize the edges of important terrain and features in remote sensing images. In addition, the spatio-temporally synchronized module is used to fuse the difference and superposition relationships between bitemporal features, and an innovative correlation mapping weighting algorithm is proposed to evaluate the similarity and difference of the fused features. Finally, the feature decoding complementary module is proposed to combine and complement features at different scales to further refine the already fused bichronological remote sensing features. The network results are optimized by the deep supervision (DS) strategy, which ensures the model's high efficiency and accuracy. CTST outperforms mainstream and state-of-the-art methods on all three datasets, with an F1 of 92.08% and an IoU of 85.33 on the LEVIR-CD dataset, an F1 of 93.25% and an IoU of 87.36% on the WHU-CD dataset, and an F1 of 93.25% and an IoU of 87.36% on the GZ-CD dataset. CD dataset the F1 is 85.95% and IoU is 75.37%, Param is 31.87 M, and FLOPS is 29.58 G.

Abstract Glioma cell sensitivity to temozolomide (TMZ) is critical for effective treatment and correlates with patient survival, although mechanisms underlying this activity are unclear. Here, we reveal a new mechanism used by glioma cells to modulate TMZ sensitivity via regulation of SORBS2 and DDR1 genes by super-enhancer RNA LINC02454. We report that LINC02454 activity increases glioma cell TMZ sensitivity by maintaining long-range chromatin interactions between SORBS2 and the LINC02454 enhancer. By contrast, LINC02454 activity also decreased glioma cell TMZ sensitivity by promoting DDR1 expression. Our study suggests a bivalent function for super-enhancer RNA LINC02454 in regulating glioma cell sensitivity to TMZ.

The goal of RGB-D salient object detection is to aggregate the information of the two modalities of RGB and depth to accurately detect and segment salient objects. Existing RGB-D SOD models can extract the multilevel features of single modality well and can also integrate cross-modal features, but it can rarely handle both at the same time. To tap into and make the most of the correlations of intra- and inter-modality information, in this paper, we proposed an attention-guided cross-modal multi-feature aggregation network for RGB-D SOD. Our motivation was that both cross-modal feature fusion and multilevel feature fusion are crucial for RGB-D SOD task. The main innovation of this work lies in two points: One is the cross-modal pyramid feature interaction (CPFI) module that integrates multilevel features from both RGB and depth modalities in a bottom-up manner, and the other is cross-modal feature decoder (CMFD) that aggregates the fused features to generate the final saliency map. Extensive experiments on six benchmark datasets showed that the proposed attention-guided cross-modal multiple feature aggregation network (ACFPA-Net) achieved competitive performance over 15 state of the art (SOTA) RGB-D SOD methods, both qualitatively and quantitatively.

Due to its simple structure and stable operation, the Organic Rankine Cycle (ORC) has gained significant attention as a primary solution for low-grade thermal power generation. However, the economic challenges associated with development difficulties in hot dry rock (HDR) geothermal power systems have necessitated a better balance between performance and cost effectiveness within ORC systems. This paper establishes a game pattern of the Organic Rankine Cycle with performance as the master layer and economy as the slave layer, based on the Stackelberg game theory. The optimal working fluid for the ORC is identified as R600. At the R600 mass flow rate of 50 kg/s, the net system cycle work is 4186 kW, the generation efficiency is 14.52%, and the levelized cost of energy is 0.0176 USD/kWh. The research establishes an optimization method for the Organic Rankine Cycle based on the Stackelberg game framework, where the network of the system is the primary optimization objective, and the heat transfer areas of the evaporator and condenser serve as the secondary optimization objective. An iterative solving method is utilized to achieve equilibrium between the performance and economy of the ORC system. The proposed method is validated through a case study utilizing hot dry rock data from Qinghai Gonghe, allowing for a thorough analysis of the working fluid and system parameters. The findings indicate that the proposed approach effectively balances ORC performance with economic considerations, thereby enhancing the overall revenue of the HDR power system.

Abstract The remarkable successes of graphene have sparked increasing interest in elemental two‐dimensional (2D) materials, also referred to as Xenes. Due to their chemical simplicity and appealing physiochemical properties, Xenes have shown particular potential for numerous (opto) electronic, iontronic, and energy applications. Among them, layered α‐phase tellurene has demonstrated the most promise, thanks to the recent successes in the chemical synthesis of highly crystalline 2D tellurene. However, the general electronic and electrochemical properties of tellurene in electrolyte systems remain ambiguous, hindering their further development. In this work, we studied the electrostatic gating, electrocatalysis, and electrochemical stability of tellurene in electrolyte systems. Our results show that tellurene obtained from both hydrothermal and chemical vapor deposition methods, two mainstream synthetic approaches for Xenes, demonstrates thickness‐dependent ambipolar transport with high hole mobility and stability in both aqueous electrolytes and ionic liquids. More importantly, the electrochemical properties of tellurene are investigated via the emerging on‐chip electrochemistry. Pristine tellurene demonstrates hydrogen evolution reaction with low Tafel slopes and remarkable electrochemical stability in acidic electrolytes over a large potential window. Our study provides a comprehensive understanding of the iontronic and electrochemical properties of tellurene, paving the way for the broad adoption of Xenes in sensors, synaptic devices, and electrocatalysis.

BackgroundOccupational commitment (OC) is a multidimensional construct that predicts turnover intentions. The interindividual variability of nurses’ OC merits further exploration. Therefore, this study aims to examine patterns of OC and its relationship with psychological empowerment and job crafting in nurses.MethodsA sample of 1,061 nurses was recruited from February 2022 to April 2022 by using a stratified four-stage cluster sampling procedure. A self-report survey included the Psychological Empowerment Scale, Job Crafting Scale, and Occupational Commitment Scale. Latent profile analysis (LPA) was used to examine the patterns of OC. Associations of the latent class membership with individual characteristics, psychological empowerment and job crafting were examined using multinomial logistic regression.ResultsThree patterns of OC were identified: (1) “Low OC group” (n = 224, 21.1%); (2) “Moderate OC group” (n = 665, 62.7%); (3) “High OC group” (n = 172, 16.2%). Nurses with higher education, fewer years of service, working in medicine, lower psychological empowerment and lower job crafting had a higher likelihood of belonging to Class 1 (Low OC group). In contrast, nurses working in emergency and with higher psychological empowerment and job crafting were more likely to belong to Class 3 (High OC group).ConclusionThe findings revealed the heterogeneity of occupational commitment among nurses in China and could guide the identification and early intervention of nurses with low level of occupational commitment.

Background: Ophthalmological screening for cytomegalovirus retinitis (CMVR) for HIV/AIDS patients is important to prevent lifelong blindness. Previous studies have shown good properties of automated CMVR screening using digital fundus images. However, the application of a deep learning (DL) system to CMVR with ultra-wide-field (UWF) fundus images has not been studied, and the feasibility and efficiency of this method are uncertain. Methods: In this study, we developed, internally validated, externally validated, and prospectively validated a DL system to detect AIDS-related from UWF fundus images from different clinical datasets. We independently used the InceptionResnetV2 network to develop and internally validate a DL system for identifying active CMVR, inactive CMVR, and non-CMVR in 6960 UWF fundus images from 862 AIDS patients and validated the system in a prospective and an external validation data set using the area under the curve (AUC), accuracy, sensitivity, and specificity. A heat map identified the most important area (lesions) used by the DL system for differentiating CMVR. Results: The DL system showed AUCs of 0.945 (95 % confidence interval [CI]: 0.929, 0.962), 0.964 (95 % CI: 0.870, 0.999) and 0.968 (95 % CI: 0.860, 1.000) for detecting active CMVR from non-CMVR and 0.923 (95 % CI: 0.908, 0.938), 0.902 (0.857, 0.948) and 0.884 (0.851, 0.917) for detecting active CMVR from non-CMVR in the internal cross-validation, external validation, and prospective validation, respectively. Deep learning performed promisingly in screening CMVR. It also showed the ability to differentiate active CMVR from non-CMVR and inactive CMVR as well as to identify active CMVR and inactive CMVR from non-CMVR (all AUCs in the three independent data sets >0.900). The heat maps successfully highlighted lesion locations. Conclusions: Our UWF fundus image-based DL system showed reliable performance for screening AIDS-related CMVR showing its potential for screening CMVR in HIV/AIDS patients, especially in the absence of ophthalmic resources.

Summary: Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b+CD11c+ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.

Abstract Owing to the availability of sensor data, the operation and maintenance (O&M) of sustainable energy systems have become more intelligent. In particular, data‐driven approaches have gained growing interest in supporting intelligent O&M. However, this is not a simple task, as the deficiency of labelled data poses a major challenge. This work proposes a self‐supervised pre‐training approach for autonomous learning of the Supervisory Control and Data Acquisition (SCADA) data representations for photovoltaic (PV) systems. Specifically, the proposed method first constructs the sample pairs using reasonable assumptions from a large volume of unlabelled SCADA data. Then, it designs a deep Siamese network to extract the representations of the input sample pair and sets the pretext task to measure whether the input pair is similar. The proposed method has been deployed in a PV system with nominal power 2.5 MW located in North China. Experimental results show that the proposed approach achieves accurate similarity assessment for the sample pairs and can potentially support downstream tasks regarding intelligent O&M.

The segmentation of fundus tumors is critical for ophthalmic diagnosis and treatment, yet it presents unique challenges due to the variability in lesion size and shape. Our study introduces Fundus Tumor Segmentation Network (FTSNet), a novel segmentation network designed to address these challenges by leveraging classification results and prompt learning. Our key innovation is the multiscale feature extractor and the dynamic prompt head. Multiscale feature extractors are proficient in eliciting a spectrum of feature information from the original image across disparate scales. This proficiency is fundamental for deciphering the subtle details and patterns embedded in the image at multiple levels of granularity. Meanwhile, a dynamic prompt head is engineered to engender bespoke segmentation heads for each image, customizing the segmentation process to align with the distinctive attributes of the image under consideration. We also present the Fundus Tumor Segmentation (FTS) dataset, comprising 254 pairs of fundus images with tumor lesions and reference segmentations. Experiments demonstrate FTSNet’s superior performance over existing methods, achieving a mean Intersection over Union (mIoU) of 0.8254 and mean Dice (mDice) of 0.9042. The results highlight the potential of our approach in advancing the accuracy and efficiency of fundus tumor segmentation.

The plectin gene can encode a cytoskeletal linking protein, plectin, known for its interaction with three critical components of the cellular cytoskeleton: intermediate filaments, microtubules, and actin filaments. In recent years, more and more studies have reported that plectin is closely related to tumorigenesis and development, exhibiting both tumor-suppressive and tumor-promoting functions. Here, we first introduce the molecular structure and function of plectin, and then we summarize the current understanding of the crucial role of plectin in cancer progression. Finally, we also discuss the possible reasons for the different roles of plectin expression in various types of cancer and highlight the double-edged sword role of plectin in tumor progression. The review aims to deepen the comprehensive understanding of plectin’s role in cancer and further help to develop novel therapeutic strategies and drug targets.

Preserving the privacy of the ever-increasing multimedia data on the cloud while providing accurate and fast retrieval services has become a hot topic in information security. However, existing relevant schemes still have significant room for improvement in accuracy and speed. Therefore, this paper proposes a privacy-preserving image–text retrieval scheme called PITR. To enhance model performance with minimal parameter training, we freeze all parameters of a multimodal pre-trained model and incorporate trainable modules along with either a general adapter or a specialized adapter, which are used to enhance the model’s ability to perform zero-shot image classification and cross-modal retrieval in general or specialized datasets, respectively. To preserve the privacy of outsourced data on the cloud and the privacy of the user’s retrieval process, we employ asymmetric scalar-product-preserving encryption technology suitable for inner product calculation, and we employ distributed index storage technology and construct a two-level security model. We construct a hierarchical index structure to speed up query matching among massive high-dimensional index vectors. Experimental results demonstrate that our scheme can provide users with secure, accurate, fast cross-modal retrieval service while preserving data privacy.

Objectives: In this study, we aimed to evaluate the non-inferiority of a quadrivalent influenza vaccine (QIV) developed by Sinovac Biotech Co., Ltd. (Sinovac, Beijing, China) by comparing its immunogenicity and safety with a comparator QIV (Vaxigrip Tetra®) in a population aged 3 years and older in Chile and the Philippines. Methods: A phase 3, non-inferiority, double-blind, randomized controlled, multicenter clinical trial was conducted in the southern hemisphere (SH) 2023 influenza season. Participants aged ≥ 3 years old with stable health were randomized 1:1 to receive either Sinovac QIV or comparator QIV. The co-primary outcomes were immunological non-inferiority for Sinovac QIV versus the comparator against each strain contained in the vaccines in terms of seroconversion rates (SCRs) and geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies 28 days after final vaccination. Results: A total of 2039 participants were vaccinated (1019 Sinovac QIV; 1020 comparator QIV). Sinovac QIV induced non-inferior immune responses to all four strains as compared to comparator QIV, with slightly higher GMTs than those of comparator QIV: GMT ratios (lower limit 95% confidence interval (CI)) were 1.8 (1.6) for A(H1N1), 1.4 (1.3) for A (H3N2), 1.3 (1.1) for B Victoria and 1.2 (1.1) for B Yamagata; observed seroconversion rate differences (lower limit 95% CI) were 9.6% (6.7) for A(H1N1), 7.0% (3.5) for A(H3N2), 2.4% (−0.03) for B Victoria and 6.8% (3.0) for B Yamagata. Adverse reactions were similar across the two groups and no vaccine-related serious adverse events were reported. Conclusions: The immunogenicity of Sinovac QIV was non-inferior to that of the comparator QIV in these populations aged 3 years and older, and safety was comparable.

Abstract Background Screening for hyperthyroidism using gold-standard diagnostic criteria in the general population is not cost-effective, leading to a relatively high rate of undiagnosed and untreated patients. This study aimed to establish a deep learning-based system to detect hyperthyroidism based on retinal photographs. Methods The multicenter, observational study included retinal photographs taken from participants in two hospitals and 24 health care centers throughout China. We first trained two models to identify hyperthyroidism: in model #1, the non-hyperthyroidism individuals were randomly selected, while in model #2, the non-hyperthyroidism group was matched for age and gender with the hyperthyroidism group. After internal validation, we selected the better model for further evaluation using external validation datasets. Results The study included 22,940 retinal photographs of 11,409 participants for the model development, and 3862 retinal photographs (1870 participants) which were obtained from two hospitals and four medical centers as the external validation datasets. Model #1 achieved a higher area under the receiver operator curve (AUC) than model #2 (0.907, 95% CI: 0.894–0.918 versus 0.850, 95% CI: 0.832–0.866) in the internal validation so that model #1 was used for further evaluation. In external datasets, model #1 reached AUCs ranging from 0.816 (95% CI 0.789–0.846) to 0.849 (95% CI 0.824–0.874) and achieved accuracies between 0.735 (95% CI 0.700–0.773) and 0.796 (95% CI 0.765–0.824). Heatmaps showed a focus of the DL-algorism on large fundus vessels and the optic nerve head. Conclusions Retinal fundus photographs may serve for DL systems for a cost-effective and non-invasive method to detect hyperthyroidism.

Abstract Background Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. Methods Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins’ expression and localization was detected by western blot and immunofluorescence. Results NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes’ transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. Conclusions Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs’ function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation. Graphical Abstract

Abstract The impact of Tim-3 (T cell immunoglobulin and mucin domain-containing protein 3) on cisplatin-induced acute kidney injury was investigated in this study. Cisplatin-induced Tim-3 expression in mice kidney tissues and proximal tubule-derived BUMPT cells in a time-dependent manner. Compared with wild-type mice, Tim-3 knockout mice have higher levels of serum creatinine and urea nitrogen, enhanced TUNEL staining signals, more severe 8-OHdG (8-hydroxy-2’ -deoxyguanosine) accumulation, and increased cleavage of caspase 3. The purified soluble Tim-3 (sTim-3) protein was used to intervene in cisplatin-stimulated BUMPT cells by competitively binding to the Tim-3 ligand. sTim-3 obviously increased the cisplatin-induced cell apoptosis. Under cisplatin treatment conditions, Tim-3 knockout or sTim-3 promoted the expression of TNF-α (tumor necrosis factor-alpha) and IL-1β (Interleukin-1 beta) and inhibited the expression of IL-10 (interleukin-10). NF-κB (nuclear factor kappa light chain enhancer of activated B cells) P65 inhibitor PDTC or TPCA1 lowed the increased levels of creatinine and BUN (blood urea nitrogen) in cisplatin-treated Tim-3 knockout mice serum and the increased cleavage of caspase 3 in sTim-3 and cisplatin-treated BUMPT cells. Moreover, sTim-3 enhanced mitochondrial oxidative stress in cisplatin-induced BUMPT cells, which can be mitigated by PDTC. These data indicate that Tim-3 may protect against renal injury by inhibiting NF-κB-mediated inflammation and oxidative stress.

ABSTRACTThe emergence of high-virulent Acinetobacter baumannii strains increases the mortality of patients and seriously affects their prognosis, which motivates us to explore novel ways to control such infections. In this study, gas chromatography–mass spectrometry was adopted to explore the metabolic difference between high- and low-virulent A. baumannii strains, and the decreased L-serine levels were identified as the most crucial biomarker in low-virulent A. baumannii strains. In vitro, L-serine reduced the virulence of A. baumannii to Beas 2B cells and inhibited the activation of NLRP3 inflammasome via decreasing the generation of ROS and mtROS and the release of inflammatory cytokines (IL-18 and IL-1β) through upregulating SIRT1. In vivo, the Galleria mellonella model was adopted. L-serine downregulated the levels of virulence genes (ompA, carO, and omp33-36), reduced the mortality of A. baumannii to G. mellonella, and decreased the blacking speed as well as the degree of G. mellonella after infection. Taken together, we found that L-serine can reduce the virulence of A. baumannii and enhance the host’s defense against the pathogen, providing a novel strategy for the treatment of infections caused by A. baumannii.IMPORTANCEAcinetobacter baumannii has become one of the most common and severe opportunistic pathogens in hospitals. The high-virulent A. baumannii strains pose a great threat to patients and increase the risk of nosocomial infection. However, the mechanism of virulence in A. baumannii is still not well understood. In the present study, we identified potential biomarkers in low-virulent A. baumannii strains. Our analysis revealed the effect of L-serine on reducing the virulence of A.baumannii. This discovery suggests that targeting L-serine could be a promising strategy for the treatment or adjunctive treatment of A. baumannii infections. The development of treatments targeting virulence may provide a substitute for the increasingly failed traditional antibacterial treatment.

Purpose: The assessment of tear film and ocular surface conditions in patients with acquired immunodeficiency syndrome (AIDS) has been poorly studied thus far. We aim to assess tear film parameters, ocular surface characteristics, and dry eye disease (DED) symptoms of patients with AIDS who did not undergo highly active antiretroviral treatment (HAART). Methods: This case–control study included 154 age-, sex-, and ethnicity-matched healthy controls and patients with AIDS. All participants underwent comprehensive ocular surface assessment and subjective DED symptomology evaluation. Data were collected between March 2022 and July 2022. Results: HAART-naïve patients with AIDS had a shorter noninvasive tear film breakup time (median 3.76 vs. 8.54 s), thinner tear film lipid layer thickness (median 73.00 vs. 91.00 nm), and lower Schirmer I test values (median 5.00 mm/5 min vs. 12.00 mm/5 min) (all P < 0.001). Moreover, higher corneal fluorescein staining scores (median 1.00 vs. 0.00) and higher upper, lower, and total meibomian gland grades were observed in AIDS patients (all P < 0.05). Negative correlations between the blood viral load and the Ocular Surface Disease Index score (r = -3.50, P = 0.027) and the Schirmer I test score (r = -0.374, P = 0.017) were detected in patients with AIDS. Conclusion: Altered tear film status was observed in individuals with HAART-naïve AIDS, even when there were no other ocular symptoms present. Therefore, patients with AIDS should be encouraged to undergo comprehensive ocular surface examinations to detect any subclinical tear film alterations occurring.

Field Programmable Gate Arrays (FPGAs) are integrated circuits that can be configured by the user after manufacturing, making them suitable for customized hardware prototypes, a feature not available in general-purpose processors in Application Specific Integrated Circuits (ASIC). In this paper, we review the vast Machine Learning (ML) algorithms implemented on FPGAs to increase performance and capabilities in healthcare technology over 2001–2023. In particular, we focus on real-time ML algorithms targeted to FPGAs and hybrid System-on-a-chip (SoC) FPGA architectures for biomedical applications. We discuss how previous works have customized and optimized their ML algorithm and FPGA designs to address the putative embedded systems challenges of limited memory, hardware, and power resources while maintaining scalability to accommodate different network sizes and topologies. We provide a synthesis of articles implementing classifiers and regression algorithms, as they are significant algorithms that cover a wide range of ML algorithms used for biomedical applications. This article is written to inform the biomedical engineering and FPGA design communities to advance knowledge of FPGA-enabled ML accelerators for biomedical applications.