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Abstract Background Transdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity. Results We fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility. Conclusions The present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.

Abstract Background Trio-based whole-exome sequencing (trio-WES) enables identification of pathogenic variants, including copy-number variants (CNVs), in children with unexplained neurodevelopmental delay (NDD) and neurodevelopmental comorbidities (NDCs), including autism spectrum disorder (ASD), epilepsy, and attention deficit hyperactivity disorder. Further phenotypic and genetic analysis on trio-WES-tested NDD-NDCs cases may help to identify key phenotypic factors related to higher diagnostic yield of using trio-WES and novel risk genes associated with NDCs in clinical settings. Methods In this study, we retrospectively performed phenotypic analysis on 163 trio-WES-tested NDD-NDCs children to determine the phenotypic differences between genetically diagnosed and non-genetically diagnosed groups. Additionally, we conducted genetic analysis of ASD genes with the help of Simons Foundation for Autism Research Institute (SFARI) Gene database to identify novel possible ASD-risk genes underlying genetic NDD conditions. Results Among these 163 patients, pathogenic variants were identified in 82 cases (82/163, 50.3%), including 20 cases with CNVs. By comparing phenotypic variables between genetically diagnosed group (82 cases) and non-genetically diagnosed group (81 cases) with multivariate binary logistic regression analysis, we revealed that NDD-NDCs cases presenting with severe-profound NDD [53/82 vs 17/81, adjusted-OR (95%CI): 4.865 (2.213 – 10.694), adjusted-P < 0.001] or having multiple NDCs [26/82 vs 8/81, adjusted-OR (95%CI): 3.731 (1.399 – 9.950), adjusted-P = 0.009] or accompanying ASD [64/82 vs 35/81, adjusted-OR (95%CI): 3.256 (1.479 – 7.168), adjusted-P = 0.003] and head circumference abnormality [33/82 vs 11/81, adjusted-OR (95%CI): 2.788 (1.148 – 6.774), adjusted-P = 0.024] were more likely to have a genetic diagnosis using trio-WES. Moreover, 37 genes with monogenetic variants were identified in 48 patients genetically diagnosed with NDD-ASD, and 15 dosage-sensitive genes were identified in 16 individuals with NDD-ASD carrying CNVs. Most of those genes had been proven to be ASD-related genes. However, some of them (9 genes) were not proven sufficiently to correlate with ASD. By literature review and constructing protein-protein interaction networks among these 9 candidate ASD-risk genes and 102 established ASD genes obtained from the SFARI Gene database, we identified CUL4B, KCNH1, and PLA2G6 as novel possible ASD-risk genes underlying genetic NDD conditions. Conclusions Trio-WES testing is recommended for patients with unexplained NDD-NDCs that have severe-profound NDD or multiple NDCs, particularly those with accompanying ASD and head circumference abnormality, as these independent factors may increase the likelihood of genetic diagnosis using trio-WES. Moreover, NDD patients with pathogenic variants in CUL4B, KCNH1 and PLA2G6 should be aware of potential risks of developing ASD during their disease courses.

Abstract Background Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. Results By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. Conclusions Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.

High entropy alloys (HEAs) have a good application potential in the preparation of high temperature service parts with complex shapes in additive manufacturing. Powder bed fusion (PBF) is a prominent type of additive manufacturing process that utilizes the thermal energy to bind powder materials together to build up plastic or metallic parts. However, the traditional gas atomization method (GA) often produce alloy powder (containing refractory element) with uneven composition, affecting the quality and performance of specimens. That is why innovative or opposite classical production powder methods are in demand for the PBF. It is worth noting that mechanical alloying technology overcomes the limitation of high temperature alloying of HEA containing refractory elements and realizes solid alloying of insoluble elements. In this paper, high entropy alloy Ni6W2Cr4Fe8Ti1 containing refractory elements is designed by means of composition control. Its spherical powders with uniform composition were successfully prepared by the new mechanical alloying - high temperature remelting spheroidization dual process (DP) method. The treated powder composition is evenly distributed with particle sizes ranging from 15 to 28 μm. And the spheroidization rate has exceeded 98.23% at 1943 K. The sample value of YS and UTS on Ni6W2Cr4Fe8Ti1 (DP-SLM) has increased by 35.7%, 45.5% and 27.3%, respectively in additive manufacturing, compared to GA-SLM. The ability to produce refractory HEA through DP method will make it possible to manufacture complex geometry shapes at a reasonable cost. It offers theoretical guidance to manufacture fine grain materials with high strength and ductility of new HEA components.

Abstract Background Most colorectal cancers originate from precancerous polyps. This study aimed to determine the prevalence of colorectal polyps with diverse pathological morphologies and to explore the risk factors for colorectal carcinoma in situ (CCS) and neoplastic polyps. Methods Inpatients admitted from January 2018 to May 2023 were screened through the hospital information system. Polyps were classified according to pathological morphology. The prevalence of polyps was described by frequency and 95% confidence interval. Univariate and multivariate logistic regression analyses were used to explore the risk factors for CCS and neoplastic polyps. Results In total, 2329 individuals with 3550 polyps were recruited. Among all patients, 76.99% had neoplastic polyps and 44.31% had advanced adenomas. Tubular adenoma had the highest prevalence at 60.15%, and the prevalence of CCS was 3.86%. Patients with a colorectal polyp diameter ≥ 1.0 cm or number ≥ 3 were 8.07 times or 1.98 times more likely to develop CCS than were those with a diameter 1.0 cm) or multifocal polyps. The levels of the tumor markers CA724 and CA211 show some potential usefulness for predicting CCS and may be exploited for early identification of high-risk populations.

Obesity is affecting global health with multiple complications, including cardiac dysfunction. Currently, it is uncertain whether drug therapy should be applied in the early stages of obesity-induced cardiac dysfunction, with weight reduction as the first choice. Sleeve gastrectomy (SG) has been widely used to treat obesity and its complications, showing promising results. However, it remains unclear whether SG can alleviate obesity-induced cardiac dysfunction. A sudden decline in body weight and food intake was observed in both the obese and obese + SG groups, with a higher rate of increase observed in the Obese group. Elevated levels of plasma glucose, serum insulin, and glycated haemoglobin in obese rats were significantly reduced by SG. Markedly increased levels of alanine transaminase, aspartate transaminase, alkaline phosphatase albumin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, elevated values of heart rate, left ventricular end-systolic pressure, left ventricular end-diastolic pressure, systolic pressure, and end diastolic pressure, and decreased value of stroke volume were observed in obese rats, which were sharply reversed by SG. Furthermore, enhanced pathological changes, including inflammatory cell infiltration and loss of cytoplasm striations, enhanced oil red O staining, increased TUNEL-positive cells, upregulated Bax and cleaved-caspase-3, and downregulated Bcl-2, were observed in obese rats, which were notably alleviated by SG. Lastly, the increased levels of relative proteins observed in obese rats were significantly reduced by SG. In conclusion, SG improved cardiac function and glucose-lipid metabolism disorders in obese rats induced by a high-fat and high-sugar diet.

Abstract Background Remodeling eubiosis of the gut microenvironment may contribute to preventing the occurrence and development of depression. Mounting experimental evidence has shown that complement C3 signaling is associated with the pathogenesis of depression, and disruption of the gut microbiota may be an underlying cause of complement system activation. However, the mechanism by which complement C3 participates in gut-brain crosstalk in the pathogenesis of depression remains unknown. Results In the present study, we found that chronic unpredictable mild stress (CUMS)-induced mice exhibited obvious depression-like behavior as well as cognitive impairment, which was associated with significant gut dysbiosis, especially enrichment of Proteobacteria and elevation of microbiota-derived lipopolysaccharides (LPS). In addition, peripheral and central complement C3 activation and central C3/CR3-mediated aberrant synaptic pruning in microglia have also been observed. Transplantation of gut microbiota from CUMS-induced depression model mice into specific pathogen-free and germ-free mice induced depression-like behavior and concomitant cognitive impairment in the recipient mice, accompanied by increased activation of the complement C3/CR3 pathway in the prefrontal cortex and abnormalities in microglia-mediated synaptic pruning. Conversely, antidepressants and fecal microbiota transplantation from antidepressant-treated donors improved depression-like behaviors and restored gut microbiome disturbances in depressed mice. Concurrently, inhibition of the complement C3/CR3 pathway, amelioration of abnormal microglia-mediated synaptic pruning, and increased expression of the synapsin and postsynaptic density protein 95 were observed. Collectively, our results revealed that gut dysbiosis induces the development of depression-like behaviors through abnormal synapse pruning in microglia-mediated by complement C3, and the inhibition of abnormal synaptic pruning is the key to targeting microbes to treat depression. Conclusions Our findings provide novel insights into the involvement of complement C3/CR3 signaling and aberrant synaptic pruning of chemotactic microglia in gut-brain crosstalk in the pathogenesis of depression. Video Abstract

Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.

BackgroundAs one of the most prevalent primary lung tumors, non-small cell lung cancer (NSCLC) has garnered considerable research interest due to its high metastasis rates and poor prognosis outcomes. Across different cancer types, metabolic processes are required for tumors progression and growth, thus interfering with such processes in NSCLC may therapeutically viable for limiting/halting disease progression. Therefore, comprehending how metabolic processes contribute to growth and survival mechanisms in cancers, including NSCLC, may elucidate key functions underpinning tumor cell metabolism. However, no bibliometric analyses have been published in this field, therefore we address this knowledge gap here.MethodsBetween 2013 and 2023 (December 28th), articles related to the NSCLC and metabolism (NSCLC-Met) field were retrieved from the Web of Science Core Collection (WoSCC). To fully dissect NSCLC-Met research directions and articles, we used the Bibliometrix package in R, VOSviewer and CiteSpace software to visually represent global trends and hotspots.ResultsBetween 2013 and 2023, 2,246 NSCLC-Met articles were retrieved, with a continuous upward trend and rapid development observed year on year. Cancers published the most articles, with Cancer Research recording the highest average citation numbers. Zhang Li from China was the most prolific author, but the highest number of authors came from the USA. China, USA, and Italy were the top three countries with the highest number of published articles, with close cooperation identified between countries. Recent hotspots and research directions were reflected by “lung adenocarcinoma”, “immunotherapy”, “nivolumab”, “checkpoint inhibitors”, “blockade”, and “pembrolizumab”, while “gut microbiome”, “egfr” and “dose painting” were important topics for researchers.ConclusionFrom our analyses, scientists can now explore new hotspots and research directions in the NSCLC-Met field. Further in-depth research in this field will undoubtedly provide more new insights on disease diagnostics, treatment, and prognostics.

Abstract Metallofullerenes are an important type of metallic nanomaterial with promising applications in several medical fields. Thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), is an important treatment strategy for advanced hepatocellular carcinoma (HCC). The thermal expansion of fullerenes makes them good adjuncts to thermal ablation treatment of HCC. In this study, we used an innovative method of emulsification and cross-linking to produce CS-C60-Fe3O4 (Chitosan-C60-Fe3O4) nanoparticles, which have the advantages of uniform particle size and high bioavailability, as a kind of novel nano-pharmaceutical. The CS-C60-Fe3O4 nanoparticles were prepared by the cross-linking reaction from chitosan–acetic acid solution, Fe3O4 nanoparticles by Fe2SO4·7H2O and FeCl3·6H2O, and C60. The average particle size of CS-C60-Fe3O4 was 194.3 nm. Because CS-C60-Fe3O4 is magnetic, it can achieve specific and tissue aggregation in HCC tumor tissues. Moreover, compared with normal soluble C60 (EL35-C60), CS-C60-Fe3O4 prolonged the retention time of C60 in the blood of mice. CS-C60-Fe3O4 alone is not cytotoxic to cultured cells or tumor tissues, but when combined with thermal ablation strategies (RFA and MWA), it significantly upregulates the antitumor effects of thermal ablation on HCC tissues, that is, it acts as a sensitiser to thermal ablation. In the presence of thermal ablation, CS-C60-Fe3O4 interfered with iron metabolism in HCC cells and induced ferroptosis of HCC cells in the tumor tissues. These results not only expand our understanding of metallofullerenes but also provide additional options for the treatment of advanced HCC.

Bipolar disorder (BD) is a psychiatric disorder that affects an increasing number of people worldwide. The mechanisms of BD are unclear, but some studies have suggested that it may be related to genetic factors with high heritability. Moreover, research has shown that chronic stress can contribute to the development of major illnesses. In this paper, we used bioinformatics methods to analyze the possible mechanisms of chronic stress affecting BD through various aspects. We obtained gene expression data from postmortem brains of BD patients and healthy controls in datasets GSE12649 and GSE53987, and we identified 11 chronic stress-related genes (CSRGs) that were differentially expressed in BD. Then, we screened five biomarkers (IGFBP6, ALOX5AP, MAOA, AIF1 and TRPM3) using machine learning models. We further validated the expression and diagnostic value of the biomarkers in other datasets (GSE5388 and GSE78936) and performed functional enrichment analysis, regulatory network analysis and drug prediction based on the biomarkers. Our bioinformatics analysis revealed that chronic stress can affect the occurrence and development of BD through many aspects, including monoamine oxidase production and decomposition, neuroinflammation, ion permeability, pain perception and others. In this paper, we confirm the importance of studying the genetic influences of chronic stress on BD and other psychiatric disorders and suggested that biomarkers related to chronic stress may be potential diagnostic tools and therapeutic targets for BD.

AbstractBackground It is possible that neonates with pneumonia also have unrecognized sepsis. Identifying sepsis in neonates with pneumonia may cause some trouble for clinicians. This study aimed to evaluate the clinical value of the procalcitonin-to-albumin ratio (PAR) in identifying sepsis in neonates with pneumonia.Methods We retrospectively included 912 neonates with pneumonia from January 2016 to July 2021. Clinical and laboratory data were collected from electronic medical records. Among neonates with pneumonia, 561 neonates were diagnosed with sepsis, according to the International Pediatric Sepsis Consensus. Neonates were divided into a sepsis group and a pneumonia group. A multivariate logistic regression analysis was used to evaluate whether PAR was a potential independent indicator for identifying sepsis in neonates with pneumonia. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of PAR in sepsis.Results Neonates with sepsis have a higher PAR (p

Introduction: Osteoporosis is the most common bone disorder where the hyperactive osteoclasts represent the leading role during the pathogenesis. Targeting hyperactive osteoclasts is currently the primary therapeutic strategy. However, concerns about the long-term efficacy and side effects of current frontline treatments persist. Alternative therapeutic agents are still needed. Objectives: Obacunone (OB) is a small molecule with a broad spectrum of biological activities, particularly antioxidant and anti-inflammatory effects. This study aims to examine OB’s therapeutic potential on osteoporosis and explore the rudimentary mechanisms. Methods: Osteoclast formation and osteoclastic resorption assays were carried out to examine OB’s inhibitory effects in vitro, followed by the in-vivo studies of OB’s therapeutic effects on ovariectomy-induced osteoporotic preclinical model. To further study the underlying mechanisms, mRNA sequencing and analysis were used to investigate the changes of downstream pathways. The molecular targets of OB were predicted, and in-silico docking analysis was performed. Ligand-target binding was verified by surface plasmon resonance (SPR) assay and Western Blotting assay. Results: The results indicated that OB suppressed the formation of osteoclast and its resorptive function in vitro. Mechanistically, OB interacts with macrophage migration inhibitory factor (MIF) which attenuates receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced signaling pathways, including reactive oxygen species (ROS), NF-κB pathway, and mitogen-activated protein kinases (MAPKs). These effects eventually caused the diminished expression level of the master transcriptional factor of osteoclastogenesis, nuclear factor of activated T cells 1 (NFATc1), and its downstream osteoclast-specific proteins. Furthermore, our data revealed that OB alleviated estrogen deficiency-induced osteoporosis by targeting MIF and thus inhibiting hyperactive osteoclasts in vivo. Conclusion: These results together implicated that OB may represent as a therapeutic candidate for bone disorders caused by osteoclasts, such as osteoporosis.

Silk, a popular luxury textile with many years of history, is easy to embrittle and adsorb bacteria when stored for a long time or exposed to sunlight, which affects its service life. To improve the silk fabrics with excellent antibacterial activity, washing and aging durability, and UV shielding, multifunctional silk fabrics were designed and fabricated via a green finishing approach. Here, we proposed a simple strategy to fabricate silk fabrics with multi-functions via coating clavate-shaped ZnO nanoparticles (ZF-silk fabrics) by dipping and pressing for cycles. The scanning electron microscope (SEM), fourier transform infrared (FTIR), ultraviolet visible spectrophotometry (UV–Vis), and X-ray diffraction (XRD) were used to analyze the structure and properties of fabricated ZF-silk fabrics. Compared with raw silk fabric, the fabricated ZF-silk fabrics represented excellent UV shielding, good tensile strength, and superior antibacterial activity. Notably, the ZF-silk fabrics had good washing stability and aging resistance. In addition, the ZF-silk fabrics possessed superior antibacterial activity before and after aging treatment (under UV radiation for 72 h). Therefore, the durable and multifunctional ZF-silk fabrics indicate great potential for achieving to realize a long service life of the fabrics.

IntroductionSeed coat color is a significant agronomic trait in horticultural crops such as Brassica rapa which is characterized by brown or yellow seed coat coloration. Previous Brassica rapa studies have shown that BrTTG1 is responsible for seed coat proanthocyanidin formation, which is dependent on the MYB-bHLH-WD40 complex, whereas some studies have reported that TRANSPARENT TESTA GLABRA 1 (TTG1) directly interacts with the structural gene promoters of the flavonoid pathway. MethodsHerein, the brown-seeded inbred B147 and ttg1 yellow-seeded inbred B80 mutants were used as plant materials for gene expression level analysis, gene promoter clone and transient overexpression.ResultsThe analysis identified eleven structural genes involved in the flavonoid biosynthesis pathway, which are potentially responsible for BrTTG1- dependent seed coat proanthocyanidin formation. The promoters of these genes were cloned and cis-acting elements were identified. Yeast one-hybrid and dual-luciferase assays confirmed that BrTTG1 directly and independently interacted with proCHS-Bra008792, proDFR-Bra027457, proTT12-Bra003361, proTT19-Bra008570, proTT19-Bra023602 and proAHA10-Bra016610. A TTG1-binding motif (RTWWGTRGM) was also identified. Overexpression of TTG1 in the yellow-seed B. rapa inbred induced proanthocyanidin accumulation by increasing the expression levels of related genes. DiscussionOur study unveiled, for the first time, the direct interaction between TTG1 and the promoters of the flavonoid biosynthesis pathway structural genes and glutathione S-transferases in Brassica rapa. Additionally, we have identified a novel TTG1-binding motif, providing a basis for further exploration into the function of TTG1 and the accumulation of proanthocyanidins in seed coats.

Urbanization has led to increased construction of underground buildings to overcome limited surface space. However, safety concerns in urban underground commercial buildings have become a major issue due to frequent accidents. Ensuring safe evacuation in densely populated underground commercial buildings is crucial. This study focuses on the safe evacuation of an urban underground commercial street A in Fuzhou City. A simulation framework based on Building Information Modelling (BIM) is proposed, integrating the Fire Dynamic Simulator (FDS) and BIM. The framework overcomes limitations in fire dynamic simulators. Using a BIM model, the study analyzes the risk of each fire protection area and selects the most unfavorable area for simulation. PyroSim technology is employed to study the entire fire development process in the underground commercial street under three different fire scenarios. The analysis includes evacuation stair travel time and personnel available safe evacuation time (TASET). By comparing the results, the study optimizes building layout design and identifies factors affecting personnel evacuation efficiency. The simulation outcomes aim to minimize casualties and property losses, contributing to fire safety management in urban underground commercial streets.

Forest aboveground biomass (AGB) is crucial as it serves as a fundamental indicator of the productivity, biodiversity, and carbon storage of forest ecosystems. This paper presents a targeted literature review of advancements in AGB estimation methods. We conducted an extensive review of published literature using Web of Science, ResearchGate, Semantic Scholar, and Google Scholar. Our findings highlight the importance of accurate AGB estimation in the studies of terrestrial carbon cycle, forest ecosystem management, and climate change. Moreover, AGB estimation contributes valuable ecological knowledge and supports effective natural resource management. Unfortunately, during the data collection process for AGB estimation, we have identified two critical yet often overlooked issues: (1) the reliability of manual survey accuracy, and (2) the impact of overlap between ground plots and remote sensing pixels on AGB estimation. Drawing on existing technologies and literature analysis, we propose a potentially effective solution to address these challenges. In conclusion, accurate estimation and mapping of forest parameters, such as AGB, will remain a priority in forestry research for the foreseeable future. To ensure the practical applicability of AGB research findings, our future research efforts will focus on understanding manual survey accuracy and determining the optimal overlap between plots and pixels.

Abstract Flexible aqueous zinc batteries (FAZBs) with high safety and environmental friendliness are promising smart power sources for smart wearable electronics. However, the bare zinc anode usually suffers from damnable dendrite growth and rampant side reaction on the surface, greatly impeding practical applications in FAZBs. Herein, a composite polymer interface layer is artificially self‐assembled on the surface of the zinc anode by graft‐modified fluorinated monomer (polyacrylic acid‐2‐(Trifluoromethyl)propenoic acid, PAA‐TFPA), on which an organic–inorganic hybrid (PAA‐Zn/ZnF2) solid electrolyte interface (SEI) with excellent ionic conductivity is formed by interacting with Zn2+. Both the pouch cell and fiber zinc anode exhibit excellent plating/stripping reversibility after protecting by this organic–inorganic SEI, which can be stably cycled more than 3000 h in symmetric Zn||Zn cells or 550 h in fiber Zn||Zn cells. Additionally, this interface layer preserves zinc anode with excellent mechanical durability under various mechanical deformation (stably working for another 1200 h after bending 100 h). The corresponding PAA‐Zn/ZnF2@Zn||MnO2 full cell displays an ultra‐long life span (79% capacity retention after 3000 cycles) and mechanical robustness (85% of the initial capacity for another 3000 cycles after bending 100 times). More importantly, the as‐assembled cells can easily power smart wearable devices to monitor the user's health condition.

Abstract Ephrin receptor A2 (EphA2) plays dual functions in tumorigenesis through ligand-independent tumor promotion or ligand-dependent tumor suppression. However, the regulation of EphA2 tumor-suppressive function remains unclear. Here, we showed that RNF5 interacts with EphA2 and induces its ubiquitination and degradation, decreases the stability and cell surface distribution of EphA2 and alters the balance of its phosphorylation at S897 and Y772. In turn, RNF5 inhibition decreases ERK phosphorylation and increases p53 expression through an increase in the EphA2 level in HER2-negative breast cancer cells. Consequently, RNF5 inhibition increases the adhesion and decreases the migration of HER2-negative breast cancer cells, and RNF5 silencing suppresses the growth of xenograft tumors derived from ER-positive, HER2-negative breast cancer cells with increased EphA2 expression and altered phosphorylation. RNF5 expression is inversely correlated with EphA2 expression in breast cancers, and a high EphA2 level accompanied by a low RNF5 level is related to better survival in patients with ER-positive, HER2-negative breast cancers. These studies revealed that RNF5 negatively regulates EphA2 properties and suppresses its tumor-suppressive function in HER2-negative breast cancers.

The nuclear-encoded factors and the photosynthetic apparatus have been studied extensively during chloroplast biogenesis. However, many questions regarding these processes remain unanswered, particularly in perennial woody plants. As a model material of woody plants, poplar not only has very significant value of research, but also possesses economic and ecological properties. This study reports the Populus trichocarpa DJ-1C (PtrDJ1C) factor, encoded by a nuclear gene, and a member of the DJ-1 superfamily. PtrDJ1C knock-out with the CRISPR/Cas9 system resulted in different albino phenotypes. Chlorophyll fluorescence and immunoblot analyses showed that the levels of photosynthetic complex proteins decreased significantly. Moreover, the transcript level of plastid-encoded RNA polymerase-dependent genes and the splicing efficiency of several introns were affected in the mutant line. Furthermore, rRNA accumulation was abnormal, leading to developmental defects in chloroplasts and affecting lignin accumulation. We concluded that the PtrDJ1C protein is essential for early chloroplast development and lignin deposition in poplar.

Abstract Background Hydrosalpinx may decrease implantation and pregnancy rates after embryo transfer. Laparoscopic tubal ligation after embryo freeze and before frozen-thawed embryo transfer (FET) is effective at improving reproductive outcomes for hydrosalpinx patients. This study is to find out the optimal interval between laparoscopic tubal ligation and FET. Methods We retrospectively analyzed 259 infertile women who performed laparoscopic tubal ligation for embryo freeze and FET. Participants were divided into three groups, based on the interval between laparoscopic tubal ligation and FET. Group I: 60 days. Outcomes of cleavage-stage and blastocyst-stage embryo FET were analyzed respectively. Results There was no significant difference in clinical pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate, ectopic pregnancy rate, miscarriage rate and preterm birth rate among the three groups, in both cleavage-stage and blastocyst-stage embryo FET cycles. In cleavage-stage embryo FET cycle, singleton gestational age was significantly younger in group III (38.11 ± 2.28 weeks) compared with group I (39.29 ± 1.06 weeks, P = 0.001) and group II (38.96 ± 1.05, P = 0.026). Singleton birth weight was significantly heavier in group II (3.65 ± 0.32 Kg) compared with group I (3.38 ± 0.29 Kg, P = 0.001) and group III (3.35 ± 0.60 Kg, P = 0.004). Twin birth weight was significantly heavier in group III (2.72 ± 0.43 Kg) compared to group I (2.23 ± 0.67 Kg, P = 0.002). In blastocyst-stage embryo FET cycles, twin gestational age was significantly younger in group II (34.07 ± 3.18 weeks) compared with group I (35.56 ± 2.27 weeks, P = 0.049) and group III (36.50 ± 1.47 weeks, P = 0.005). Twin birth weight was significantly heavier in group III (2.71 ± 0.39 Kg) compared to group II (2.39 ± 0.67 Kg, P = 0.009). Conclusions The duration of the interval between laparoscopic tubal ligation and FET does not affect the reproductive outcomes; however, it may affect the neonate outcomes to some extent.

The advancement of virtual coupling technology in urban rail transit has facilitated the online coupling and decoupling of trains, enabling a range of flexible transportation configurations, including various route types and adjustable formations. This study targets the fluctuating passenger demands on urban rail lines, aiming to minimize both passenger travel and operational costs. The model integrates constraints associated with virtual coupling, train operations, rolling stock circulation, and the interaction between virtually coupled trains and passenger arrivals. New decision variables are introduced to depict the train formation state under virtual coupling scenarios. An integrated optimization model for train diagrams and rolling stock circulation under virtual coupling conditions is developed, employing a genetic-simulated annealing algorithm informed by train operation simulations. A case study on an urban rail line during the morning peak examines the optimization of train diagrams for full-length and short-turn routes. Findings confirm that virtual coupling technology effectively adapts to lines with uneven passenger flow distribution, significantly enhancing the match between supply and demand, equalizing spatial and temporal traffic variations, and harmonizing the quality of passenger services with operational efficiency.

Researching and developing a new type of diaphragm wall foundation can solve the probl em that the traditional diaphragm wall structure may not meet the high standards of safety and stability of underground structures in some specific engineering environments. This paper focuses on the horizontal bearing characteristic of a new form of foundation, a strip-walled underground diaphragm wall, through a series of model tests. In the tests, nine plexiglass models with different section sizes, wall spacings and wall heights, as well as loading strategies (horizontal loads along and against the wall in the model), were conducted. The influence of the above factors on the horizontal bearing performance of the foundation and the soil resistance distribution around the wall was studied. The results show that when the horizontal load applied along the wall is greater than 50 N, the growth rate of total displacement at the top of the wall gradually decreases; when a horizontal load is applied against the wall, with a uniform change in wall height, the optimal wall spacing is 11 cm. When the same displacement occurs, the bearing performance of the model under the former loading strategy is generally 10% higher than that under the later loading strategy. In addition, the depth where the maximum bending moment along the wall occurred gradually moves downward with the increase in horizontal load, and the increase in wall spacing and wall height has a positive effect on the horizontal bearing characteristic. With the application of load, the maximum bending moment of the wall will gradually decrease along the depth. The increase in wall spacing and wall height can improve the overall flexural stiffness and horizontal bearing performance of the foundation. Lastly, the group wall effect coefficient, β, is put forward, and a simplified formula for calculating the horizontal bearing capacity of a strip wall foundation is proposed. In the formula, β is negatively correlated with the buried depth of the wall and positively correlated with the distance between the walls, and its coefficient is greater than 1.

Simplified methods of static free head stiffness of the semi-rigid foundation under lateral loads were limited to flexible or rigid behavior by the critical length of piles. This would lead to errors when predicting the static or dynamic performance of their upper structures in OWT Systems. This paper presents a comprehensive analysis of the head static stiffness of the semi-rigid pile without considering the critical length. Firstly, case studies using the energy-based variational method encompassing nearly twenty thousand cases were conducted. These cases involved different types of foundations, including steel pipe piles and concrete caissons, in three types of soil: homogeneous soil, linearly inhomogeneous soil, and heterogeneous soil. Through the analysis of these cases, a series of polynomial equations of three kinds of head static stiffness, containing the relative stiffness of the pile and soil, the slenderness ratio, and Poisson’s ratio, were developed to capture the semi-rigid behavior of the foundations. Furthermore, the lateral deflection, the rotation for concrete caissons in the bridge projects, and several natural frequencies of three cases about the OWT system considering the SSI effect were carried out. the error of high-order frequency of the OWT system reached 13% after considering the semi-rigid effect of the foundation.

Smoke control technology is crucial in the risk management of fire in underground confined spaces. In this study, the integrated foam smoke reduction device (FSRD) of “foaming–spraying” is proposed in response to the challenging problem of smoke control of fire in underground confined spaces. The overall structure of FSRD device is designed and optimized through the numerical simulation of the internal flow field and experimental research. The optimal basic parameters are as follows: area ratio (Rm) of 20.25, pitch-to-diameter ratio (Rtd) of 1/3 or 5/9, and throat diameter (d3) of 18 mm . Additionally, the throat–nozzle distance (Lt) is 12 mm, and the operating pressure (p0) is 3.0 MPa. Finally, the smoke reduction experiment verified that the FSRD designed in this study had a better effect of elimination than fine water mist and cylindrical foam jet, with the elimination efficiency reaching 36.73%. This study provides a new device for smoke reduction in controlling fires in underground confined spaces.

Bone marrow edema-like lesions (BMEL) in the knee have been linked to the symptoms and progression of osteoarthritis (OA), a highly prevalent disease with profound public health implications. Manual and semi-automatic segmentations of BMELs in magnetic resonance images (MRI) have been used to quantify the significance of BMELs. However, their utilization is hampered by the labor-intensive and time-consuming nature of the process as well as by annotator bias, especially since BMELs exhibit various sizes and irregular shapes with diffuse signal that lead to poor intra- and inter-rater reliability. In this study, we propose a novel unsupervised method for fully automated segmentation of BMELs that leverages conditional diffusion models, multiple MRI sequences that have different contrast of BMELs, and anomaly detection that do not rely on costly and error-prone annotations. We also analyze BMEL segmentation annotations from multiple experts, reporting intra-/inter-rater variability and setting better benchmarks for BMEL segmentation performance.

Most traditional synthetic dyes and functional reagents used in silk fabrics are not biodegradable and lack green environmental protection. Natural dyes have attracted more and more attention because of their coloring, functionalization effects, and environmental benefits. In this study, natural dyes were extracted from lac and used for coloring and functionalization in silk fabrics without any other harmful dyes. The extraction conditions were studied and analyzed by the univariate method. The optimal extraction process was that the volume ratio of ethanol to water was 60:40 with a solid–liquid ratio of 1:10, and reacting under the neutrality condition for 1 h at 70 °C. Silk fabric can be dyed dark owing to the certain lifting property of lac. After being dyed by Al3+ post-medium, the levels of the washing fastness, light fastness, and friction fastness of silk fabric are all above four with excellent fastness. The results show that the dyed silk fabrics have good UV protection, antioxidation, and antibacterial properties. The UV protection coefficient UPF is 42.68, the antioxidant property is 98.57%, and the antibacterial property can reach more than 80%. Therefore, the dyeing and functionalization of silk fabrics by utilizing naturally lac dyes show broad prospects in terms of the application of green sustainable dyeing and functionalization.

In various analytical models, modeling the behavior of large-diameter monopiles and piles can be challenging due to these foundations with huge body sizes carrying mechanisms of lateral loads to the surrounding soils. In this paper, the transfer matrix method with the Timoshenko beam theory was used to modify the shear rotation of pile sections under different loading stages, including serviceability limit stages and the ultimate loading stage. In this transfer matrix method, a large-diameter pile is considered according to the Timoshenko beam theory, and the recurring variables in the matrix equation are replaced with constants to simplify the calculation steps. Two model test cases were used to verify the accuracy of the method. Then, a series of comparisons between the Timoshenko beam and the Euler–Bernoulli beam theories, with the relative pile–soil stiffness being equal to 0.15, 0.45, and 0.75, was conducted to investigate the differences in pile response after considering the shear deformation. The results show that the effect of shear deformation of large-diameter piles changes with different loading levels. The values of the pile deformation based on the Timoshenko beam theory divided by those of that based on the Euler–Bernoulli beam theory were in the range of 1.0 to 1.10, and they increased slightly with increasing loads, reaching their maximum value, and then rapidly decreased to 1.0 when close to the ultimate lateral load; the maximum value was influenced by the relative pile–soil stiffness. Furthermore, the ratio of the shear rotation of the pile section to the slope of the deflection curve was in the range of 1.0 to 1.10; these also showed similar but more moderate trends compared with the values of pile deformation based on the Timoshenko beam theory divided by those of that based on the Euler–Bernoulli beam theory.

ContextPotentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, "light touch", approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.ObjectivesThe objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer's Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.MethodsThe D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.ConclusionThis large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia. ClinicalTrials.gov Identifier: NCT05147428.

BackgroundEchocardiography-guided percutaneous intramyocardial alginate-hydrogel implantation (PIMAHI) is a novel treatment approach for heart failure (HF). We validated PIMAHI safety and efficacy in canine HF models.MethodsFourteen canines with HF [produced by coronary artery ligation, left ventricular ejection fraction (LVEF)

ABSTRACT Phosphorylation, a significant posttranslational modification, is implicated in nearly two-thirds of all proteins. The involvement of phosphorylation in various cellular responses is known to play a crucial role in the replication of pseudorabies virus (PRV). However, the phosphoproteomic landscape during PRV infection remains unknown. To address this, a tandem mass tag-based liquid chromatography-tandem mass spectrometry was performed. It was found that a total of 7,342 phosphosites were detected; among these, 1,197 phosphosites were significantly upregulated, and 1,120 phosphosites were significantly downregulated when the threshold was set at 1.5. Gene ontology analysis of these significantly changed proteins showed that they mainly participated in mRNA processing, RNA splicing, stress granule assembly, and other pathways. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that these proteins were associated with cell cycle, spliceosome, tight junction, mRNA surveillance, and other pathways. Additionally, an immunoblotting assay confirmed the phosphoproteomic results by detecting the protein level of several upregulated phosphorylated proteins, which included pBRAF, pRPS6KA1, and pSTMN1. Further experiments using siRNA showed that knockdown of BRAF, RPS6KA1, and STMN1 significantly inhibited the replication of PRV. In summary, this study provides insight into the phosphoproteomic landscape during PRV infection and contributes to a better understanding of the mechanisms underlying PRV replication. IMPORTANCE Pseudorabies virus (PRV) is a kind of alpha herpesvirus that infects a wide range of animals and even human beings. Therefore, it is important to explore the mechanisms behind PRV replication and pathogenesis. By conducting a tandem mass tag-based phosphoproteome, this study revealed the phosphorylated proteins and cellular response pathways involved in PRV infection. Findings from this study shed light on the relationship between the phosphorylated cellular proteins and PRV infection, as well as guiding the discovery of targets for the development of antiviral compounds against PRV.

A reasonable calculation of railway capacity is very important for research. With the rapid development of high-speed railways, more and more differences between traditional and modern railways have emerged in the transportation organization and capacity calculation methods. In this article, the calculation methods used under different conditions with different train types are studied based on the train deduction method. Train deduction is a method that calculates the number of trains that cannot pass through the line when other trains change their stop plan or operation speed based on the coefficient of deduction method, which is widely used in China. Then, optimized models for trains with the same-speed and different-speeds are built to determine the maximum number of trains. These models are built based on the constraints of passenger service quality and overtaking times. In addition, the models are solved based on a train operation plan. Hence, the capacity calculated by these methods is more reasonable for the actual condition. Finally, an actual case of Beijing–Shanghai high-speed railway is implemented and tested with the model. The optimal capacity scheme is simulated and analysed, and the result agreed well with the railway transport enterprise. First published online 5 February 2024

ABSTRACTIntroduction The sigma metric offers a quantitative framework for evaluating process performance in clinical laboratories. This study aimed to evaluate the analytical performance of automated analysers in haematology laboratories, using the sigma metric to choose the best analyser as an internal reference analyser.Materials and Methods internal quality control (IQC) data were collected for 6 months from SNCS, and the sigma value was calculated for 9 haematology analysers in the laboratory.Results For the normal control level, a satisfactory mean sigma value ≥3 was observed for all of the studied parameters of all automated analysers. For the low control level, platelet (PLT) count by Instrument (Inst.) G performed poorly, with a mean sigma value 4, performed best and was chosen as the internal reference analyser.Conclusion The sigma metric can be used as a guide to choose the QC strategy and plan QC frequency. It can facilitate the comparison of the same assay performed by multiple systems.

The inevitable thick cloud contamination in Landsat images has severely limited the usability and applications of these images. Developing cloud removal algorithms has been a hot research topic in recent years. Many previous algorithms used one or multiple cloud-free image(s) in the same area acquired on other date(s) as reference image(s) to reconstruct missing pixel values. However, it remains challenging to determine the optimal reference image(s). In addition, abrupt land cover change can substantially degrade the reconstruction accuracies. To address these issues, we present a new cloud removal algorithm called Virtual Image-based Cloud Removal (VICR). For each cloud region, VICR reconstructs the missing surface reflectance by three steps: virtual image within cloud region construction based on time-series reference images, similar pixel selection using the newly proposed temporally weighted spectral distance (TWSD), and residual image estimation. By establishing two buffer zones around the cloud region, VICR allows automatic selection of the optimal set of time-series reference images. The effectiveness of VICR was validated at four testing sites with different landscapes (i.e. urban, croplands, and wetlands) and land change patterns (i.e. phenological change, abrupt change caused by flooding and tidal inundation), and the performances were compared with mNSPI (modified neighborhood similar pixel interpolator), WLR (weighted linear regression) and ARRC (AutoRegression to Remove Clouds). Experimental results showed that VICR outperformed the other algorithms and achieved higher Correlation Coefficients and lower Root Mean Square Errors in surface reflectance estimation at the four sites. The improvement is particularly noticeable at the sites with abrupt land change. By considering the difference in the contributions from the reference images, TWSD can select more reliable similar pixels to improve the prediction of abrupt change in surface reflectance. Moreover, VICR is more robust to different cloud sizes and to changing reference images. VICR is also computationally much faster than ARRC. The framework for time-series image cloud removal by VICR has great potential to be applied for large datasets processing.

Beijing has undergone severe settlement in recent years. Persistent Scatterers Interferometric Synthetic Aperture Radar (PS-InSAR) technique has been widely used to derive time-series land deformation. However, existing studies have faced two challenges: (1) the nonlinear characteristics of time-series subsidence has not been fully investigated; (2) since PS points are normally distributed in urban areas with high building density, measurement gaps usually exist in nonurban areas. To address the challenges, we presented a new method to reconstruct spatially continuous time-series deformation. First, PS-InSAR was used to retrieve the deformation based on 135 scenes of Envisat ASAR and Radarsat-2 images from 2003 to 2020. Polynomial Curve Fitting (PCF) was then used to model nonlinear time-series deformation for the PS points. In the PS measurement gaps, Iterative Self-Organizing Data Analysis Technique (ISODATA) and Multi-output Least Squares Support Vector Regression (MLS-SVR) were used to estimate the PCF coefficients and then time-series deformation considering 40 features including thickness of the compressible layers, annual groundwater level, etc. The major results showed that (1) compared to linear, quadratic, and quartic models, cubic polynomial model generated better fit for the time-series deformation (R2 ≈0.99), suggesting obvious nonlinear temporal pattern of deformation; (2) the time-series deformation over measurement gaps reconstructed by ISODATA and MLS-SVR had satisfactory accuracy (R2 = 0.92, MAPE

Study region: Beijing-Tianjin-Hebei (BTH) region, China Study focus: BTH has long been suffering from severe and uneven land subsidence. Finding out the spatial evolution of land subsidence is helpful to collaborative prevention and control. We innovatively revealed the spatial distribution of land subsidence from the mountains to the coastal area along four hydrogeological profiles, and inferred the land subsidence mechanism on the overall scale, local plain scale and typical regional scale. Small Baseline Subsets Interferometric Synthetic Aperture Radar was employed to collect displacement information in the BTH region from January 2012 to January 2020. We obtained groundwater storage data from the Gravity Recovery and Climate Experiment. New hydrological insights for the region: On the overall scale, from 2012 to 2019, the Changping-TongZhou district of Beijing suffered the most serious land subsidence, with an annual subsidence rate of 159 mm and a cumulative subsidence as high as 928 mm. On the local plain scale, areas experiencing severe subsidence were generally located in the central plain. Fractures in the area obviously influenced the spatial distribution of subsidence. On the typical regional scale, a positive correlation was found between land subsidence and groundwater depletion. The relationship between precipitation and land subsidence in Hebei was the most convincing (R2 = 0.64). This study provides a scientific basis for regional coordination in land subsidence control. Data availability: Data can be provided by the corresponding authors upon request.

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKKα/β, subsequently leading to IRF3 and NF-κB phosphorylation. However, the specific E3 ubiquitin ligase for MDA5 K63-polyubiquitination has not been well characterized. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral immune agents indicates that SARS-CoV-2 escapes from antiviral immune responses via several unknown mechanisms. Here, we report that SARS-CoV-2 nonstructural protein 8 (nsp8) acts as a suppressor of antiviral innate immune and inflammatory responses to promote infection of SARS-CoV-2. It downregulates the expression of type I interferon, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and TRIM4 and impairing TRIM4-mediated MDA5 K63-linked polyubiquitination. Our findings reveal that nsp8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Curcumol is a natural drug isolated from Chinese medicinal plant Rhizoma Curcumae. Though many studies have revealed its anti-tumor mechanism, there are still few studies reveal its comprehensive anti-cancer effect used multi-omics method. In this study, we aim to comprehensively analyze its anti-cancer mechanism and find its potential target in human hepatocellular carcinoma cells (HCC). In total, 1330 differential genes and 1381 differential proteins were significantly altered by curcumol in HCC. Transcriptomics and proteomics combined analysis revealed that 47 downregulated of the 97 common molecules regulated by curcumol were mainly enriched in the cell cycle pathway, including Cell Division Cycle Associated 2 (CDCA2), CDCA3, CDCA8, CDC25C, S-phase kinase-associated protein 2 (SKP2) and Polo-like kinase 1(PLK1). Furthermore, silenced PLK1 inhibited the cell growth and reversed curcumol’s effect on HCC. This paper provided a comprehensive understanding of the effect of curcumol and identified PLK1 was its potential target in HCC cells.

Reasonable adjustment of crop acreage can improve the sustainability of agriculture in arid zones by promoting economic development, alleviating water scarcity, and improving resource utilization efficiency but meets the challenges of various decision-maker preferences and uncertainties. With the objectives of maximizing economic benefits, minimizing evapotranspiration, and maximizing water productivity and water production efficiency, this study developed a grey entropy based multi-objective fuzzy constraint interval programming model (GEMOFCIP) through incorporation of information entropy technology, fuzzy constraints and interval programming approaches within a general optimization framework. The model is capable of (1) generating the crop acreage management schemes through trading off the different development goals; (2) dealing with the structure and parameter uncertainties of the optimization model; (3) measuring the relative importance of multiple objectives by the introduction of information entropy with the insufficient decision-maker’s preference information. Taking the crop acreage planning problem in Liangzhou, northwest China as a case study, the model was solved under different water-saving and satisfaction degree scenarios. It turned out that, after optimization, the economic benefit, water productivity and water production efficiency have been significantly improved, while the total ET and the total irrigation water have been significantly compressed in the study area. The GEMOFCIP model is superior to the previous models in that it takes into account the randomness of the relative importance of system objective, the vagueness of system constraints and the fluctuations of system coefficients, which would make the model more reasonable, stable and objective. Optimal results can help manage crop pattern with the economy-resource-efficiency consideration and accelerate the healthy development of agriculture in arid zones.

Abstract Background Artificial intelligence (AI) has been introduced to interpret the panoramic radiographs (PRs). The aim of this study was to develop an AI framework to diagnose multiple dental diseases on PRs, and to initially evaluate its performance. Methods The AI framework was developed based on 2 deep convolutional neural networks (CNNs), BDU-Net and nnU-Net. 1996 PRs were used for training. Diagnostic evaluation was performed on a separate evaluation dataset including 282 PRs. Sensitivity, specificity, Youden’s index, the area under the curve (AUC), and diagnostic time were calculated. Dentists with 3 different levels of seniority (H: high, M: medium, L: low) diagnosed the same evaluation dataset independently. Mann-Whitney U test and Delong test were conducted for statistical analysis (ɑ=0.05). Results Sensitivity, specificity, and Youden’s index of the framework for diagnosing 5 diseases were 0.964, 0.996, 0.960 (impacted teeth), 0.953, 0.998, 0.951 (full crowns), 0.871, 0.999, 0.870 (residual roots), 0.885, 0.994, 0.879 (missing teeth), and 0.554, 0.990, 0.544 (caries), respectively. AUC of the framework for the diseases were 0.980 (95%CI: 0.976–0.983, impacted teeth), 0.975 (95%CI: 0.972–0.978, full crowns), and 0.935 (95%CI: 0.929–0.940, residual roots), 0.939 (95%CI: 0.934–0.944, missing teeth), and 0.772 (95%CI: 0.764–0.781, caries), respectively. AUC of the AI framework was comparable to that of all dentists in diagnosing residual roots (p > 0.05), and its AUC values were similar to (p > 0.05) or better than (p

Cotton Verticillium wilt is a common fungal disease during the growth of cotton, leading to the yellowing of leaves, stem dryness, and root rot, severely affecting the yield and quality of cotton. Current monitoring methods for Verticillium wilt mainly rely on manual inspection and field investigation, which are inefficient and costly, and the methods of applying pesticides in cotton fields are singular, with issues of low pesticide efficiency and uneven application. This study aims to combine UAV remote sensing monitoring of cotton Verticillium wilt with the precision spraying characteristics of agricultural drones, to provide a methodological reference for monitoring and precision application of pesticides for cotton diseases. Taking the cotton fields of Shihezi City, Xinjiang as the research subject, high-resolution multispectral images were collected using drones. Simultaneously, 150 sets of field samples with varying degrees of Verticillium wilt were collected through ground data collection, utilizing data analysis methods such as partial least squares regression (PLSR) and neural network models; additionally, a cotton Verticillium wilt monitoring model based on drone remote sensing images was constructed. The results showed that the estimation accuracy R2 of the PLSR and BP neural network models based on EVI, RENDVI, SAVI, MSAVI, and RDVI vegetation indices were 0.778 and 0.817, respectively, with RMSE of 0.126 and 0.117, respectively. Based on this, an analysis of the condition of the areas to be treated was performed, combining the operational parameters of agricultural drones, resulting in a prescription map for spraying against cotton Verticillium wilt.

The tapping-mode atomic force microscope (TM-AFM) is widely used today; however, improper matching between the operating medium and the sampling time may lead to inaccurate measurement results. The relationship between the damping coefficient and the steady state of the TM-AFM microcantilever is investigated in this paper using multiple stability theory. Firstly, the effects of changes in dimensionless linear damping coefficients and dimensionless piezoelectric film damping coefficients on the motion stability of the system are examined using bifurcation diagrams, phase trajectories, and domains of attraction. Subsequently, the degrees of effect of the two damping coefficients on the stability of the system are compared. Finally, the bi-parametric bifurcation characteristics of the system under a specific number of iterative cycles are investigated using the bi-parametric bifurcation diagram in conjunction with the actual working conditions, and the boundary conditions for the transition of the system’s motion from an unstable state to a stable state are obtained. The results of the study show that to ensure the accuracy and reliability of the individual measurement data in 500 iteration cycles, the dimensionless linear damping coefficient must be greater than 0.01014. Our results will provide valuable references for TM-AFM measurement media selection, improving TM-AFM imaging quality, measurement accuracy and maneuverability, and TM-AFM troubleshooting.

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.

Abstract Background Accumulating evidence has demonstrated that arcuate nucleus (ARC) of the hypothalamus is likely responsible for the close association between chronic stress, depression, and diabetes. Xiaoyaosan (XYS), a Chinese herbal formula, remarkably improves depressive-like behavior and glucose intolerance, but the mechanism remains unclear. Leptin receptor (LepR) regulates energy expenditure and depression by mediating the action of leptin on the ARC. Therefore, we hypothesized that XYS may regulate depressive-like behavior and glucose intolerance via the leptin and its cascade LepR-STAT3/PI3K pathway in the ARC. Methods A rat model of depressive-like behavior and susceptibility to glucose intolerance was induced by exposure to chronic unpredictable mild stress (CUMS) for six weeks. XYS (2.224 g/kg) was orally gavaged for six weeks, and fluoxetine (2.0 mg/kg) was administrated to the positive control group. Depressive-like behaviors were assessed using the open field test (OFT), sucrose preference test (SPT) and forced swim test (FST). Fasting blood glucose (FBG) and oral glucose tolerance test (OGTT) were performed to evaluate the effects of XYS on blood glucose. Peripheral leptin and blood lipids were detected using enzyme-linked immunosorbent assay and an automatic biochemical analyzer, respectively. The effects of XYS on the LepR-STAT3/PI3K pathway were detected by quantitative real-time PCR and western blotting. Results XYS ameliorated CUMS-induced depressive-like behaviors and elevated blood glucose. XYS improved the food intake but have no significant effects on the body weight. Peripheral leptin and its central receptor were also suppressed by XYS, accompanied by the downregulation of JAK2/STAT3 and PI3K/AKT pathway in the ARC. Additionally, XYS increased AGRP and NPY expression but inhibited POMC in the ARC. Conclusions XYS improves depressive-like behaviors and susceptibility to glucose intolerance induced by CUMS, which may be achieved by the downregulation of the LepR-STAT3/PI3K signaling pathway in the ARC.

Abstract In the production process, the manufacturing behavior and all the essential factors are affected by several disturbance factors, showing a complex dynamic fluctuation law. It makes the stability control process a difficult problem in environmental constraints. In this paper, the workshop production process is considered, and an improved coupled map lattice workshop production network state model is proposed. On this basis, the controller with the function of resource load protection is designed, and the network state model of the workshop based on the pinning control is developed. Three kinds of stability control strategies, SAC (Self-adaption Control) , SC (Self-acting Control) and PC (Pinning Control) , are designed based on disturbance triggering behavior and node state transition rules. In addition, two control effect evaluation indexes, RTS (Recovery Time Steps) and NFT (Node Failure Times) are designed. Considering the actual production data of diesel fuel injection system parts production workshop as example, the model is simulated and verified. The results show that under different disturbance intensities, compared with the SAC strategy, the RTS-Average value of the PC strategy is reduced by 29.83% on average, and the NFT-Average values are reduced by 46.9% on average. This proves that the pinning control strategy has certain advantages in controlling time length and propagation scale of disturbance propagation.

Abstract Background Nonerythrocytic spectrin beta 1 (SPTBN1) is an important cytoskeletal protein that involves in normal cell growth and development via regulating TGFβ/Smad signaling pathway, and is aberrantly expressed in various cancer types. But, the exact role of SPTBN1 in pan-cancer is still unclear. This report aimed to display expression patterns and prognostic landscapes of SPTBN1 in human cancers, and further assess its prognostic/therapeutic value and immunological role in kidney renal carcinoma (KIRC) and uveal melanoma (UVM). Methods We firstly analyzed expression patterns and prognostic landscapes of SPTBN1 in human cancers using various databases and web-based tools. The relationships between SPTBN1 expression and survival/tumor immunity in KIRC and UVM were further investigated via R packages and TIMER 2.0 platform. The therapeutic roles of SPTBN1 in KIRC and UVM were also explored via R software. Following this, the prognostic value and cancer immunological role of SPTBN1 in KIRC and UVM were validated in our cancer patients and GEO database. Results Overall, cancer tissue had a lower expression level of SPTBN1 frequently in pan-cancer, compared with those in adjacent nontumor one. SPTBN1 expression often showed a different effect on survival in pan-cancer; upregulation of SPTBN1 was protective to the survival of KIRC individuals, which was contrary from what was found in UVM patients. In KIRC, there were significant negative associations between SPTBN1 expression and pro-tumor immune cell infiltration, including Treg cell, Th2 cell, monocyte and M2-macrophage, and expression of immune modulator genes, such as tumor necrosis factor superfamily member 9 (TNFSF9); while, in UVM, these correlations exhibited opposite patterns. The following survival and expression correlation analysis in our cancer cohorts and GEO database confirmed these previous findings. Moreover, we also found that SPTBN1 was potentially involved in the resistance of immunotherapy in KIRC, and the enhance of anti-cancer targeted treatment in UVM. Conclusions The current study presented compelling evidence that SPTBN1 might be a novel prognostic and therapy-related biomarker in KIRC and UVM, shedding new light on anti-cancer strategy.

Abstract In the article, we present multiple solutions for a second-order singular Dirichlet boundary value problem that arises when modeling the ocean flow of the Antarctic Circumpolar Current. The main tools of the proof are the Leray–Schauder nonlinear alternative principle and a well-known fixed point theorem in cones.

Adult hippocampal neurogenesis generates functional neurons from neural progenitor cells in the hippocampal dentate gyrus (DG) to complement and repair neurons and neural circuits, thus benefiting the treatment of depression. Increasing evidence has shown that aberrant microglial activity can disrupt the appropriate formation and development of functional properties of neurogenesis, which will play a crucial role in the occurrence and development of depression. However, the mechanisms of the crosstalk between microglia and adult hippocampal neurogenesis in depression are not yet fully understood. Therefore, in this review, we first introduce recent discoveries regarding the roles of microglia and adult hippocampal neurogenesis in the etiology of depression. Then, we systematically discuss the possible mechanisms of how microglia regulate adult hippocampal neurogenesis in depression according to recent studies, which involve toll-like receptors, microglial polarization, fractalkine-C-X3-C motif chemokine receptor 1, hypothalamic-pituitary-adrenal axis, cytokines, brain-derived neurotrophic factor, and the microbiota-gut-brain axis, etc. In addition, we summarize the promising drugs that could improve the adult hippocampal neurogenesis by regulating the microglia. These findings will help us understand the complicated pathological mechanisms of depression and shed light on the development of new treatment strategies for this disease.