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Abstract The hot corrosion experiments of René N5 alloy coated with three different NiCrAlY metal bonding layers are carried out, that the layers are prepared by different methods (APS, HVAF and MIP). Compared with bare René N5 alloy samples, the hot corrosion resistance of coated samples is improved. It can be attributed to the small internal stress of the surface oxide layer on the coating sample, which is difficult to spall, reducing the degree of hot corrosion reaction. The hot corrosion resistance of NiCrAlY layers is MIP > HVAF > APS, which is positively positively related to the density of layers, because the influence of element diffusion in the process of hot corrosion is effectively slowed down.

Abstract Treatment for inflammatory bowel disease (IBD) is challenging since current anti-inflammatory and immunosuppressive therapies do not address the underlying causes of the illness, which include increased levels of reactive oxygen species (ROS) and dysbiosis of the gut commensal microbiota. Additionally, these treatments often have systemic off-target effects and adverse side effects. In this study, we have developed a prebiotic yeast β-glucan nanocomplex coated with bio-adhesive polydopamine (YBNs@PDA) to effectively prolong their retention time in the gastrointestinal (GI) tract. The oral administration of YBNs@PDA restored the epithelium barriers, reduced ROS levels, and minimized systemic drug exposure while improved therapeutic efficacy in an acute colitis mouse model. Furthermore, 16S ribosomal RNA genes sequencing demonstrated a higher richness and diversity in gut microflora composition following the treatments. In particular, YBNs@PDA markedly augmented the abundance of Lachnospiraceae NK4A136 and Bifidobacterium, both of which are probiotics with crucial roles in relieving colitis via retaining gut homeostasis. Cumulatively, these results demonstrate that the potential of YBNs@PDA as a novel drug-free, ROS-scavenging and gut microbiota regulation nanoplatform for the treatment of GI disorders.

Abstract Background This study aimed to elucidate the methodology and assess the efficacy of the aortic arch inclusion technique using an artificial blood vessel in managing acute type A aortic dissection (ATAAD). Methods We conducted a retrospective review of 18 patients (11 males and 7 females, average age: 56.2 ± 8.6 years) diagnosed with ATAAD who underwent total aortic arch replacement (TAAR) using an artificial vascular “inclusion” between June 2020 and October 2022. During the operation, deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (ACP) of the right axillary artery were employed for brain protection. The ‘inclusion’ total aortic arch replacement and stented elephant trunk (SET) surgery were performed. Results Four patients underwent the Bentall procedure during the study, with one additional patient requiring coronary artery bypass grafting (CABG) due to significant involvement of the right coronary orifice. Three patients died during postoperative hospitalization. Other notable complications included two cases of postoperative renal failure necessitating continuous renal replacement therapy (CRRT), one case of postoperative double lower limb paraplegia, and one case of cerebral infarction resulting in unilateral impairment of the left upper limb. Eleven patients underwent computed tomography angiography (CTA) examinations of the aorta three months to one-year post-operation. The CTA results revealed thrombosis in the false lumen surrounding the aortic arch stent in seven patients and complete thrombosis of the false lumen around the descending aortic stent in eight patients. One patient had partial thrombosis of the false lumen around the descending aortic stent, and another patient’s false lumen in the thoracic and abdominal aorta completely resolved after one year of follow-up. Conclusions Incorporating vascular graft in aortic arch replacement simplifies the procedure and yields promising short-term outcomes. It achieves the aim of total arch replacement using a four-branch prosthetic graft. However, extensive sampling and thorough, prolonged follow-up observations are essential to fully evaluate the long-term results.

Abstract Background Tartary buckwheat (Fagopyrum tataricum) belongs to Polygonaceae family and has attracted increasing attention owing to its high nutritional value. UDP-glycosyltransferases (UGTs) glycosylate a variety of plant secondary metabolites to control many metabolic processes during plant growth and development. However, there have been no systematic reports of UGT superfamily in F. tataricum. Results We identified 173 FtUGTs in F. tataricum based on their conserved UDPGT domain. Phylogenetic analysis of FtUGTs with 73 Arabidopsis UGTs clustered them into 21 families. FtUGTs from the same family usually had similar gene structure and motif compositions. Most of FtUGTs did not contain introns or had only one intron. Tandem repeats contributed more to FtUGTs amplification than segmental duplications. Expression analysis indicates that FtUGTs are widely expressed in various tissues and likely play important roles in plant growth and development. The gene expression analysis response to different abiotic stresses showed that some FtUGTs were involved in response to drought and cadmium stress. Our study provides useful information on the UGTs in F. tataricum, and will facilitate their further study to better understand their function. Conclusions Our results provide a theoretical basis for further exploration of the functional characteristics of FtUGTs and for understanding the growth, development, and metabolic model in F. tataricum.

Abstract Background Accumulating evidence indicates that aberrant non-SMC condensin II complex subunit D3 (NCAPD3) is associated with carcinogenesis of various cancers. Nevertheless, the biological role of NCAPD3 in the pathogenesis of non-small cell lung cancer (NSCLC) remains unclear. Methods Immunohistochemistry and Western blot were performed to assess NCAPD3 expression in NSCLC tissues and cell lines. The ability of cell proliferation, invasion, and migration was evaluated by CCK-8 assays, EdU assays, Transwell assays, and scratch wound healing assays. Flow cytometry was performed to verify the cell cycle and apoptosis. RNA-sequence and rescue experiment were performed to reveal the underlying mechanisms. Results The results showed that the expression of NCAPD3 was significantly elevated in NSCLC tissues. High NCAPD3 expression in NSCLC patients was substantially associated with a worse prognosis. Functionally, knockdown of NCAPD3 resulted in cell apoptosis and cell cycle arrest in NSCLC cells as well as a significant inhibition of proliferation, invasion, and migration. Furthermore, RNA-sequencing analysis suggested that NCAPD3 contributes to NSCLC carcinogenesis by regulating PI3K/Akt/FOXO4 pathway. Insulin-like growth factors-1 (IGF-1), an activator of PI3K/Akt signaling pathway, could reverse NCAPD3 silence-mediated proliferation inhibition and apoptosis in NSCLC cells. Conclusion NCAPD3 suppresses apoptosis and promotes cell proliferation via the PI3K/Akt/FOXO4 signaling pathway, suggesting a potential use for NCAPD3 inhibitors as NSCLC therapeutics.

Abstract The pathogenesis of Parkinson’s disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-β levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.

Abstract Super enhancers (SEs) consist of clusters of enhancers, harboring an unusually high density of transcription factors, mediator coactivators and epigenetic modifications. SEs play a crucial role in the maintenance of cancer cell identity and promoting oncogenic transcription. Super enhancer lncRNAs (SE-lncRNAs) refer to either transcript from SEs locus or interact with SEs, whose transcriptional activity is highly dependent on SEs. Moreover, these SE-lncRNAs can interact with their associated enhancer regions in cis and modulate the expression of oncogenes or key signal pathways in cancers. Inhibition of SEs would be a promising therapy for cancer. In this review, we summarize the research of SE-lncRNAs in different kinds of cancers so far and decode the mechanism of SE-lncRNAs in carcinogenesis to provide novel ideas for the cancer therapy.

Abstract Aiming at the problems of slow convergence speed and low precision probability of multi-objective optimization of energy storage materials, a multi-objective optimization model of energy storage materials based on NSGA-II algorithm was proposed. The association rule set of storage materials in the joint supply chain operation performance management system is extracted, and the rough vector feature distribution set multi-objective optimization method is used to decompose and optimize the characteristics of storage materials in the joint supply chain operation performance management system. Using NSGA-II optimization analysis method, this paper summarizes the power storage materials under the joint supply chain operation performance management system, and summarizes three kinds of inventory control: periodic inventory, inventory coding, and computerized inventory. Combined with the positive regression learning method of organizational operational performance, the multi-objective optimization decision of electric storage materials under the joint supply chain operational performance management system is realized. The simulation results show that under the joint supply chain operation performance management system, the proposed method reaches the optimal convergence after 65 iterations, the convergence speed is fast, and the accuracy probability reaches 1.000 after 80 iterations, which solves the problems of slow convergence speed and low accuracy probability, and has a good scheduling ability of energy storage materials.

Abstract Background Clinical scenarios frequently present challenges when patients exhibit asymmetrical mandibular atrophy. The dilemma arises: should we adhere to the conventional All-on-4 technique, or should we contemplate placing vertically oriented implants on the side with sufficient bone mass? This study aims to employ three-dimensional finite element analysis to simulate and explore the biomechanical advantages of each approach. Methods A finite element model, derived from computed tomography (CT) data, was utilized to simulate the nonhomogeneous features of the mandible. Three configurations—All-on-4, All-on-5-v and All-on-5-o were studied. Vertical and oblique forces of 200 N were applied unilaterally, and vertical force of 100 N was applied anteriorly to simulate different masticatory mechanisms. The maximum von Mises stresses on the implant and framework were recorded, as well as the maximum equivalent strain in the peri-implant bone. Results The maximum stress values for all designs were located at the neck of the distal implant, and the maximum strains in the bone tissue were located around the distal implant. The All-on-5-o and All-on-5-v models exhibited reduced stresses and strains compared to All-on-4, highlighting the potential benefits of the additional implant. There were no considerable differences in stresses and strains between the All-on-5-o and All-on-5-v groups. Conclusions With the presence of adequate bone volume on one side and severe atrophy of the contralateral bone, while the “All-on-4 concept” is a viable approach, vertical implant placement optimizes the transfer of forces between components and tissues.

Abstract Aims Acute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia–reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury. Methods and results An in vivo MI mice model and an in vitro MI cell model was established. The expression levels were detected using quantitative real‐time PCR (qRT‐PCR) and western blot. Cellular proliferation, apoptosis, pyroptosis, and autophagy were detected by immunostaining, immunohistochemistry, western blot, and transmission electron microscopy (TEM). Dual‐luciferase reporter assay, RNA pull‐down assay, and RIP assay were performed to validate the molecular interactions. CircRbms1 was up‐regulated in A/R‐induced HCMs and acted as a sponge for miR‐142‐3p, thereby targeting MST1. CircRbms1 could improve stability of MST1 by recruiting IGF2BP2 (all P

The Gross Domestic Product (GDP) per capita is one of the most widely used socioeconomic indicators, serving as an integral component for climate change impact analysis. However, a national scale assessment may induce considerable bias because it conceals any internal variations within a country. The lack of a long-term sub-national scale GDP data is a substantive hinderance. Leveraging the close relationship between nighttime lights and GDP, we address this gap by developing a novel methodological framework in two steps. First, under the modeling philosophy of spatial statistics, we developed a novel approach based on deep and machine learning techniques to establish a complex mapping between two inconsistent nighttime lights (NTL) datasets: the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP) and the National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite (VIIRS). The models achieve accuracies ranging from 0.945 to 0.980 (correlation coefficients). By taking the estimations ensemble of the two techniques, the time series of DMSP data was extended to 2021. Next, a novel modeling strategy based on multi-layer perceptron was developed to derive the non-linear relationship between NTL and GDP per capita at sub-national scale to alleviate scale effects at this granularity, while explicitly capturing regional heterogeneity effect. The trained models achieve average accuracies of 0.967, 0.959, and 0.959 on the training, validation, and test sets, respectively. We evaluate the developed dataset at the global, national, and sub-national scales from various perspective, and the results offer solid evidence on the reliability of the estimated economic data. By linking to historical global climate change data, we quantify global economic losses attributed to extreme heat to demonstrate how the estimated GDP data can be useful in the climate change impact analysis.

Artificial light at night (ALAN) is a common form of light pollution worldwide, and the intensity, timing, duration, and wavelength of light exposure can affect biological rhythms, which can lead to metabolic, reproductive, and immune dysfunctions and consequently, host–pathogen interactions. Insect vector-borne diseases are a global problem that needs to be addressed, and ALAN plays an important role in disease transmission by affecting the habits and physiological functions of vector organisms. In this work, we describe the mechanisms by which ALAN affects host physiology and biochemistry, host–parasite interactions, and vector-borne viruses and propose preventive measures for related infectious diseases to minimize the effects of artificial light on vector-borne diseases.

Summary: Background: In order to address the low compliance and dissatisfied specificity of low-dose computed tomography (LDCT), efficient and non-invasive approaches are needed to complement its limitations for lung cancer screening and management. The ASCEND-LUNG study is a prospective two-stage case–control study designed to evaluate the performance of a liquid biopsy-based comprehensive lung cancer screening and post-screening pulmonary nodules management system. Methods: We aimed to develop a comprehensive lung cancer system called Peking University Lung Cancer Screening and Management System (PKU-LCSMS) which comprises a lung cancer screening model to identify specific populations requiring LDCT and an artificial intelligence-aided (AI-aided) pulmonary nodules diagnostic model to classify pulmonary nodules following LDCT. A dataset of 465 participants (216 cancer, 47 benign, 202 non-cancer control) were used for the two models’ development phase. For the lung cancer screening model development, cancer participants were randomly split at a ratio of 1:1 into the train and validation cohorts, and then non-cancer controls were age-matched to the cancer cases in a 1:1 ratio. Similarly, for the AI-aided pulmonary nodules model, cancer and benign participants were also randomly divided at a ratio of 2:1 into the train and validation cohorts. Subsequently, during the model validation phase, sensitivity and specificity were validated using an independent validation cohort consisting of 291 participants (140 cancer, 25 benign, 126 non-cancer control). Prospectively collected blood samples were analyzed for multi-omics including cell-free DNA (cfDNA) methylation, mutation, and serum protein. Computerized tomography (CT) images data was also obtained. Paired tissue samples were additionally analyzed for DNA methylation, DNA mutation, and messenger RNA (mRNA) expression to further explore the potential biological mechanisms. This study is registered with ClinicalTrials.gov, NCT04817046. Findings: Baseline blood samples were evaluated for the whole screening and diagnostic process. The cfDNA methylation-based lung cancer screening model exhibited the highest area under the curve (AUC) of 0.910 (95% CI, 0.869–0.950), followed by the protein model (0.891 [95% CI, 0.845–0.938]) and lastly the mutation model (0.577 [95% CI, 0.482–0.672]). Further, the final screening model, which incorporated cfDNA methylation and protein features, achieved an AUC of 0.963 (95% CI, 0.942–0.984). In the independent validation cohort, the multi-omics screening model showed a sensitivity of 99.2% (95% CI, 0.957–1.000) at a specificity of 56.3% (95% CI, 0.472–0.652). For the AI-aided pulmonary nodules diagnostic model, which incorporated cfDNA methylation and CT images features, it yielded a sensitivity of 81.1% (95% CI, 0.732–0.875), a specificity of 76.0% (95% CI, 0.549–0.906) in the independent validation cohort. Furthermore, four differentially methylated regions (DMRs) were shared in the lung cancer screening model and the AI-aided pulmonary nodules diagnostic model. Interpretation: We developed and validated a liquid biopsy-based comprehensive lung cancer screening and management system called PKU-LCSMS which combined a blood multi-omics based lung cancer screening model incorporating cfDNA methylation and protein features and an AI-aided pulmonary nodules diagnostic model integrating CT images and cfDNA methylation features in sequence to streamline the entire process of lung cancer screening and post-screening pulmonary nodules management. It might provide a promising applicable solution for lung cancer screening and management. Funding: This work was supported by Science, Science, Technology & Innovation Project of Xiongan New Area, Beijing Natural Science Foundation, CAMS Innovation Fund for Medical Sciences (CIFMS), Clinical Medicine Plus X-Young Scholars Project of Peking University, the Fundamental Research Funds for the Central Universities, Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Peking University People's Hospital Research and Development Funds, National Key Research and Development Program of China, and the fundamental research funds for the central universities.

The exposure of organic UV filters has been increasingly confirmed to induce adverse effects on humans. However, the critical exposure pathway and the vulnerable population of organic UV filters are not clearly identified. This paper attempts to evaluate the health risk of commonly used organic UV filters from various exposure routes based on comprehensive analysis strategy. The estimated daily intakes (EDI) and hazard quotient (HQ) values of organic UV filters through four pathways (dermal exposure, indoor dust, indoor air, and drinking water) for various age groups were determined. Although the total HQ values (0.01–0.4) from comprehensive exposure of organic UV filters were below risk threshold (1.0), infants were identified as the most vulnerable population, with EDI (75.71 ng/kg-bw/day) of 2–3 times higher than that of adults. Additionally, the total EDI values of individual exposure pathways were estimated and ranked as follows: indoor air (138.44 ng/kg-bw/day) > sunscreen application (37.2 ng/kg-bw/day) > drinking water (21.87 ng/kg-bw/day) > indoor dust (9.24 ng/kg-bw/day). Moreover, we successfully tailored the Sankey diagram to depict the EDI proportion of individual organic UV filters from four exposure pathways. It was noted that EHMC (ethylhexyl methoxycinnamate) and EHS (ethylhexyl salicylate) dominated the contribution of EDI (72 %) via indoor air exposure routes. This study serves as a crucial reference for enhancing public health risk awareness concerning organic UV filters, with a special focus on the vulnerable populations such as infants and children.

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.

ABSTRACT: Exposure to copper (Cu) has been associated with metabolic disorders in animals and humans, but the underlying mechanism remains unclear. One-day-old broiler chickens, numbering a total of 192, were nourished with dietary intakes that contained varying concentrations of Cu, specifically 11, 110, 220, and 330 mg/kg of Cu, for a period extending over a duration of 7 wk. As a result of the study, Cu exposure resulted in vacuolization, fragmentation of mitochondria cristae, and the increase of autophagosomes in hepatocytes. Metabolomics analysis illustrated that Cu caused a total of 59 different metabolites in liver, predominantly associated with the glycerophospholipid metabolic pathway, leading to metabolic disruption. Moreover, high-Cu diet markedly reduced the levels of AMPKα1, p-AMPKα1, mTOR, and p-mTOR and enhanced the expression levels of the autophagy-related factors (Atg5, Dynein, Beclin1, and LC3-II). Overall, Cu exposure caused chicken liver injury and resulted in disturbed metabolic processes and mediated autophagy primarily through the AMPK-mTOR axis.

ABSTRACT: Inactivated vaccines play an important role in preventing and controlling the epidemic caused by the H5 subtype avian influenza virus. The vaccine strains are updated in response to alterations in surface protein antigens, while an avian-derived vaccine internal backbone with a high replicative capacity in chicken embryonated eggs and MDCK cells is essential for vaccine development. In this study, we constructed recombinant viruses using the clade 2.3.4.4d A/chicken/Jiangsu/GY5/2017(H5N6, CkG) strain as the surface protein donor and the clade 2.3.4.4b A/duck/Jiangsu/84512/2017(H5N6, Dk8) strain with high replicative ability as an internal donor. After optimization, the integration of the M gene from the CkG into the internal genes from Dk8 (8GM) was selected as the high-yield vaccine internal backbone, as the combination improved the hemagglutinin1/nucleoprotein (HA1/NP) ratio in recombinant viruses. The r8GMΔG with attenuated hemagglutinin and neuraminidase from the CkG exhibited high-growth capacity in both chicken embryos and MDCK cell cultures. The inactivated r8GMΔG vaccine candidate also induced a higher hemagglutination inhibition antibody titer and microneutralization titer than the vaccine strain using PR8 as the internal backbone. Further, the inactivated r8GMΔG vaccine candidate provided complete protection against wild-type strain challenge. Therefore, our study provides a high-yield, easy-to-cultivate candidate donor as an internal gene backbone for vaccine development.

Water-land transition zones (WLTZs) are quintessential, complex human-land systems where aquatic and terrestrial environments intermingle, playing a pivotal role in bolstering global ecological resilience (ER). Human terrestrial production activities have encroached upon ecologically sensitive aquatic areas, weakening the inherent ER patterns in WLTZs. To address these issues, we developed an ER assessment process chain across the disturbance-carrying-recovery (D-C-R) dimensions. Applied it to the Dongting Lake region, this model diagnosed the spatiotemporal variations in ER from 2000 to 2020 and revealed the stress mechanisms of various driving factors. The results indicate: (1) The ER spatial pattern in the Dongting Lake region featured a radiating enhancement structure originating from a low-value core in the central plain’s lake network area, displaying distinct water-land gradient variations. Areas with declining ER levels were mainly distributed around the main body of the lake, water system runoff areas, and near governmental centers. (2) The spatiotemporal differentiation effects of ER manifested as an east–west axial development trend, tending toward polarization. The spatiotemporal aggregation effect appeared as L-L clustering and cold spots in the north, gradually expanding toward the peripheral forest areas. (3) Factors related to land use were the dominant drivers of spatiotemporal changes in ER. Simultaneously, the nonlinear interaction intensity among these driving factors showed a significant annual increase. This research framework can be extended to assess ER in similar regions, potentially offering policy recommendations for the ecological protection and sustainable management of WLTZs.

The disorderly expansion of human production-living construction activities into aquatic ecological sensitive areas has triggered severe production-living-ecological space (PLES) conflicts. However, research on the risk-triggering mechanisms of PLES conflicts in lake network regions and multidimensional scenario simulation techniques is relatively lacking. To address these issues, this study constructs an integrated model chain by coupling the Markov-GMOP-PLUS model to achieve a quantified diagnosis and simulated regulation of spatial conflict strength index (SCSI) under sustainable development goals. Applying it to the Dongting Lake region reveals that: (1) The overall PLES exhibited a distribution pattern where “ecological space encompasses production space, with living space interspersed within”. The category conversion mainly reflected the encroachment of agricultural production space on the plain water ecological space, with a conversion area of up to 899.48 km2. (2) The distinctive “high in the north, low in the south” PLES conflict pattern was closely aligned with the land use structure and water system distribution, with conflict hotspots persistently clustering in the core lake network regions amid rapid urbanization. Among these, the growth rate of severe conflicts in the last ten years was 3.86 times that of the previous ten years. (3) The sustainable development scenario showcased the most effective conflict mitigation by curtailing production-living space expansion and ecological space encroachment. This scenario reversed the growth trend in conflict high-value zones and the reduction trend in low-value zones, with change rates of −3.30 % and 7.05 %, respectively, compared to 2020. This study provides a scientific basis for formulating sustainable land-use policies in lake network regions.

ObjectiveThis study explored the utility of NLR (neutrophil-to-lymphocyte ratio) as a marker to predict Lower Extremity Peripheral Artery Disease (PAD) in the Chinese population, as well as to assess its consistency and diagnostic value with digital subtraction angiography.MethodsPatients were distributed into three groups according to the angiography in lower limb arterial: group L1, plaque with no stenosis; group L2, plaque with luminal stenosis and group L3, total vascular occlusion. Changes in the neutrophil-to-lymphocyte ratio were documented and compared among groups.ResultsCompared to group L1, NLR was significantly increased in L2 (1.76 vs 2.35, p=0.037) and L3 (1.76 vs 3.60, p70%) increased to 2.075 times for every 1 increase in NLR, while it was 46.8% for every 0.1 increase in ABI. The optimal NLR cut-off value to predict severe stenosis in PAD was 2.73. Receiver operating characteristic curve analysis of the inflammatory biomarkers and severe stenosis prediction displayed an area under the curve of 0.81.ConclusionNLR could serve as a new noninvasive and accurate marker in predicting PAD.

Abstract Background Pulmonary fibrosis (PF) is a common clinically critical disease characterized by high morbidity and high mortality. Forsythiaside A (FA) is a phenylethanol glycoside component in Forsythia suspensa, which has anti‐inflammatory, antioxidant, and antiviral activities. However, the effects of FA on bleomycin (BLM)‐induced PF are unclear. Purpose The present study explored the role of FA in the amelioration of oxidative stress and apoptosis in BLM‐induced PF as well as the possible underlying mechanisms, in vivo and in vitro. Methods Network pharmacology was used to collect the effects of FA on BLM‐induced PF. Subsequently, further observation of the effects of FA on mice with PF by pulmonary pathological changes, transmission electron microscopy, real‐time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. An in vitro model was constructed by inducing A549 with transforming growth factor beta‐1 (TGF‐β1) to observe the effect of FA on epithelial cell apoptosis. Results Network pharmacology predicted signaling pathways such as IL‐17 signaling pathway and Relaxin signaling pathway. The results of in vivo studies showed that FA ameliorated BLM‐induced PF through inhibition of fibrosis, modulation of apoptosis, and oxidative stress. In addition, FA promoted TGF‐β1‐induced apoptosis in A549 cells. Conclusions The results of our study suggested that FA could protect mice against BLM‐induced PF by regulating oxidative stress and apoptosis as well as the Epithelial mesenchymal transition pathway.

BackgroundTransmission-blocking vaccines (TBVs) can effectively prevent the community’s spread of malaria by targeting the antigens of mosquito sexual stage parasites. At present, only a few candidate antigens have demonstrated transmission-blocking activity (TBA) potential in P. vivax. Quiescin-sulfhydryl oxidase (QSOX) is a sexual stage protein in the rodent malaria parasite Plasmodium berghei and is associated with a critical role in protein folding by introducing disulfides into unfolded reduced proteins. Here, we reported the immunogenicity and transmission-blocking potency of the PvQSOX in P. vivax.Methods and findingsThe full-length recombinant PvQSOX protein (rPvQSOX) was expressed in the Escherichia coli expression system. The anti-rPvQSOX antibodies were generated following immunization with the rPvQSOX in rabbits. A parasite integration of the pvqsox gene into the P. berghei pbqsox gene knockout genome was developed to express full-length PvQSOX protein in P. berghei (Pv-Tr-PbQSOX). In western blot, the anti-rPvQSOX antibodies recognized the native PvQSOX protein expressed in transgenic P. berghei gametocyte and ookinete. In indirect immunofluorescence assays, the fluorescence signal was detected in the sexual stages, including gametocyte, gamete, zygote, and ookinete. Anti-rPvQSOX IgGs obviously inhibited the ookinetes and oocysts development both in vivo and in vitro using transgenic parasites. Direct membrane feeding assays of anti-rPvQSOX antibodies were conducted using four field P. vivax isolates (named isolates #1–4) in Thailand. Oocyst density in mosquitoes was significantly reduced by 32.00, 85.96, 43.52, and 66.03% with rabbit anti-rPvQSOX antibodies, respectively. The anti-rPvQSOX antibodies also showed a modest reduction of infection prevalence by 15, 15, 20, and 22.22%, respectively, as compared to the control, while the effect was insignificant. The variation in the DMFA results may be unrelated to the genetic polymorphisms. Compared to the P.vivax Salvador (Sal) I strain sequences, the pvqsox in isolate #1 showed no amino acid substitution, whereas isolates #2, #3, and #4 all had the M361I substitution.ConclusionsOur results suggest that PvQSOX could serve as a potential P. vivax TBVs candidate, which warrants further evaluation and optimization.

Abstract Triple‐negative breast cancer (TNBC) poses a challenging prognosis due to early metastasis driven by anoikis resistance. Identifying crucial regulators to overcome this resistance is vital for improving patient outcomes. In this study, a genome‐wide CRISPR/Cas9 knockout screen in TNBC cells has identified tyrosine‐protein phosphatase nonreceptor type 14 (PTPN14) as a key regulator of anoikis resistance. PTPN14 expression has shown a progressive decrease from normal breast tissue to metastatic tumors. Overexpressing PTPN14 has induced anoikis and inhibited cell proliferation in TNBC cells, while normal human breast cells are unaffected. Mechanistically, PTPN14 is identified as a key factor in dephosphorylating breast cancer antiestrogen resistance 3, a novel substrate, leading to the subsequent inhibition of PI3K/AKT and ERK signaling pathways. Local delivery of in vitro transcribed PTPN14 mRNA encapsulated by lipid nanoparticles in a TNBC mouse model has effectively inhibited tumor growth and metastasis, prolonging survival. The study underscores PTPN14 as a potential therapeutic target for metastatic TNBC, with the therapeutic strategy based on mRNA expression of PTPN14 demonstrating clinical application prospects in alleviating the burden of both primary tumors and metastatic disease.

Abstract By modulating subwavelength structures and integrating functional materials, 2D artificial microstructures (2D AMs), including heterostructures, superlattices, metasurfaces and microcavities, offer a powerful platform for significant manipulation of light fields and functions. These structures hold great promise in high‐performance and highly integrated optoelectronic devices. However, a comprehensive summary of 2D AMs remains elusive for photonics and optoelectronics. This review focuses on the latest breakthroughs in 2D AM devices, categorized into electronic devices, photonic devices, and optoelectronic devices. The control of electronic and optical properties through tuning twisted angles is discussed. Some typical strategies that enhance light‐matter interactions are introduced, covering the integration of 2D materials with external photonic structures and intrinsic polaritonic resonances. Additionally, the influences of external stimuli, such as vertical electric fields, enhanced optical fields and plasmonic confinements, on optoelectronic properties is analysed. The integrations of these devices are also thoroughly addressed. Challenges and future perspectives are summarized to stimulate research and development of 2D AMs for future photonics and optoelectronics.

Abstract Background and objectives To analyze oncological and functional results of transoral minimally invasive surgery (TMIS) for supraglottic laryngeal carcinoma (SGLC), and investigate independent prognostic factors. Methods Seventy SGLC patients treated with TMIS were included. The overall survival (OS), recurrence‐free survival (RFS), and postoperative functions were analyzed. Results Sixty‐two patients were early‐stage (Tis, T1, and T2) and eight patients were T3. Eleven patients received preoperative induction chemotherapy (IC). Sixty patients received transoral laser microsurgery (TLM), and 10 patients received transoral robotic surgery (TORS). Fifty‐eight patients were scored Grade‐1 by water swallow test, and 49 patients were scored Grade 0 by grade, roughness, breathiness, asthenia, strain. The 1, 3, and 5 year OS of all were 95.450%, 84.877%, and 78.026%, and RFS were 89.167%, 78.052%, and 75.451% respectively. Kaplan–Meier survival analysis showed N stage and clinical stage were associated with OS, smoking, clinical stage, surgical margins, and Ki‐67 index were associated with RFS. There were no significant differences in preoperative IC or direct surgery, TLM, or TORS. Cox analyses showed smoking and surgical margins were independent prognosis factors for RFS. Conclusions The positive margin, Ki‐67 index ≥40% and P53(+)&Ki‐67 index ≥40% are worse factors affecting recurrence for SGLC patients. Both smoking and surgical margins are independent prognostic factors affecting recurrence.

Abstract In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient‐derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function‐associated single‐cell RNA sequencing (FascRNA‐seq) platform allowing both phenotypic evaluation and scRNA‐seq at single‐organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA‐seq data of individual pLCOs with their responses to anti‐PD‐1 (αPD‐1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti‐tumor immunity, to identify potential tumor‐reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA‐seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.

BackgroundsAtrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF.MethodsThe cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography–tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months).ResultsSerum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P

PurposeGiven the increasing occurrence of stroke and high-sodium diets (DHIS) over the past 30 years, it is crucial to assess the global, national, and regional impact of DHIS on the burden of stroke.Methods and materialsThe Global Burden of Diseases Study 2019 provided the study's data. We used the Bayesian meta-regression tool DisMod-MR 2.1 to evaluate the burden of stroke attributable to DHIS. Age-standardized disability-adjusted life years (ASDR) and age-standardized mortality rate (ASMR) were used to quantify the burden. We perform correlation analysis utilizing the Spearman rank-order correlation method, and we calculate the estimated annual percentage change (EAPC) to evaluate temporal trends.ResultsGlobally, DHIS accounts for 17,673.33 thousand disability-adjusted life years (DALYs) and 700.98 thousand deaths of stroke in 2019. The burden of stroke attributable to DHIS has declined between 1990 and 2019 globally and in the majority of regions, with the largest declines seen in regions with high sociodemographic indexes (SDI). Both ASMR and ASDR were higher regionally in regions with moderate SDI than those in developed regions. Furthermore, the absolute values of EAPC, reflecting the rate of decrease, were notably lower in these regions compared to developed nations. High-income North America, categorized within the SDI regions, notably witnessed the smallest decline in ASDR over the last three decades. Additionally, from 1990 to 2019, males consistently bore a larger burden of stroke attributable to DHIS.ConclusionThe burden of stroke attributable to DHIS remained a major concern despite advancements in public knowledge of stroke and their utilization of emergency medical services. Over the past 30 years, more burden has been placed on males and regions with moderate SDI values; in males, higher EAPC values for both ASMR and ASDR have been found. This underscores the urgent need for effective interventions to alleviate the burden of stroke associated with DHIS.

In previous research, the prevailing assumption was that Graph Neural Networks (GNNs) precisely depicted the interconnections among nodes within the graph's architecture. Nonetheless, real-world graph datasets are often rife with noise, elements that can disseminate through the network and ultimately affect the outcome of the downstream tasks. Facing the complex fabric of real-world graphs and the myriad potential disturbances, we introduce the Sparse Graph Dynamic Attention Networks (SDGAT) in this research. SDGAT employs the L0 regularization technique to achieve a sparse representation of the graph structure, which eliminates noise and generates a more concise sparse graph. Building upon this foundation, the model integrates a dynamic attention mechanism, allowing it to selectively focus on key nodes and edges, filter out irrelevant data, and simultaneously facilitate effective feature aggregation with important neighbors. To evaluate the performance of SDGAT, we conducted experiments on three citation datasets and compared its performance against commonly employed models. The outcomes indicate that SDGAT excels in node classification tasks, notably on the Cora dataset, with an accuracy rate of 85.29%, marking a roughly 3% enhancement over the majority of baseline models. The experimental findings provide evidence that SDGAT delivers effective performance on all three citation datasets, underscoring the efficacy of the dynamic attention network built upon a sparse graph.

Summary: Background: Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors. Methods: A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c. Findings: DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson’s trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing. Interpretation: This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties. Funding: Shown in Acknowledgements.

Condition-based maintenance is very desirable for minimizing the maintenance and failure costs of power systems without sacrificing reliability. A systematic approach including an adaptive maintenance advisor and a system maintenance optimizer is proposed here for effectively handling the operational variations and uncertainties for condition-based maintenance. First, the maintenance advisor receives and implements the maintenance plans for its key components from the system maintenance optimizer, which optimizes the maintenance schedules with multi-objective evolutionary algorithm, considering only major system variables and the overall system performance. During operation, the offshore substation will experience continuing ageing and shifts in control, weather and load factors, measurement and human judgment detected from the connected grid and all other equipments with uncertainties. Then, the advisor estimates the changes of reliability indices due to operational variations and uncertainties of its key components by hierarchical fuzzy logic and sends the changes back to the maintenance optimizer. The maintenance optimizer will upgrade the load-point reliability and report any drastic deterioration of reliability within each substation, which may lead to re-optimization of the substation's maintenance activities for meeting its desired reliability. The offshore substation connected to a medium-sized onshore grid will be studied here to demonstrate the ability of this proposed approach in dealing with uncertainties in the implementation of maintenance with significant reduction of computational complexity and rule base.

Objective: The main objective of this study was to create and assess a detailed diagnostic model with an optimizing feature selection algorithm that combines computed tomography (CT) imaging characteristics, demographic information, and genetic markers to enhance the accuracy of benign and malignant classification of osteosarcoma. This research seeks to enhance the early identification and categorization of benign and malignant of osteosarcoma, ultimately enabling more personalized and efficient treatment approaches. Methods: Data from 225 patients diagnosed with osteosarcoma at two different medical institutions between June 2018 and June 2021 were gathered for this research study. A novel feature selection approach that combined Principal Component Analysis (PCA) with Improved Particle Swarm Optimization (IPSO) was utilized to analyze 1743 image-derived features. The performance of the resulting model was evaluated using metrics such as area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE), and compared to models developed using conventional feature selection methods. Results: The proposed model showed promising predictive performance with an AUC of 0.87, accuracy of 0.80, sensitivity of 0.75, and specificity of 0.85. These results suggest improved predictive ability compared to models built using traditional feature selection techniques, particularly in terms of accuracy and specificity. However, there is room for improvement in enhancing sensitivity. Conclusion: Our study introduces a novel predictive model for distinguishing between benign and malignant osteosarcoma., emphasizing its potential significance in clinical practice. Through the utilization of CT imaging features, our model shows improved accuracy and specificity, marking progress in the early detection and classification of osteosarcoma as either benign or malignant. Future investigations will concentrate on enhancing the model’s sensitivity and validating its effectiveness on a larger dataset, aiming to boost its clinical relevance and support personalized treatment approaches for osteosarcoma.

To achieve all-organic polymer with high dielectric performances, we have designed a novel side-chain liquid crystalline polymer (P7) with strong polar mesogen of (Z)-4-(2-cyano-2-phenylvinyl)benzonitrile (CSCN) attached to polycyclooctene backbone. The bis-cyano-substituted CSCN is board-shaped and exhibits a large dipole moment (8.54 D) which tilts ∼34.2° away from its molecular long axis. Consequently, CSCN shows unique dual molecular anisotropy: one from biaxial shape anisotropy and the other from polarization anisotropy. The complex phase behaviors of P7 were investigated employing mainly the techniques of differential scanning calorimetry and X-ray diffraction. Four liquid crystal (LC) phases are identified as K0, K1, K2 and K3, which are SmA, highly-ordered biaxial SmA, B5-like and B7-like, respectively, with the thermal stability increased in sequence. The experimental results indicate that the different LC phases are arisen from the competition and balance between π-π stacking and dipole-dipole interaction. While the face-to-face π-π stacking is dominant in K0 and K1, optimizing the dipole-dipole interaction causes the CSCN mesogens within the smectic layer to tilt and rotate, resulting in K2 and K3. We further investigated the dielectric properties of P7 films using polarization-electric field loops test. The dielectric constant (εr) of P7 is found to be LC structure dependent, which is increased when the LC phase is varied from K0 to K3. With an average εr of 9.7 achieved in K3 and the low dielectric loss (tan δ = 0.001), P7 film offers a promising material in advanced applications like energy storage and electronic devices.

This paper describes the two-dimensional (2D) crystallization of side-chain giant molecules (SCGMs) having the fixed number ratio of two types of functionalized building blocks with 1:1. SCGMs are regarded to a certain degree as size-amplified versions of universal synthetic polymers that are prepared by precisely connecting molecular nanoparticles (MNPs) to polymer chains. Our previous experimental results have shown that individually changing the number ratio of one of the building blocks would significantly affect the structural parameters of molecular crystals, mainly the longitudinal thickness. Herein, we systematically discussed the 2D crystallization of two categories of POSS-based SCGMs with constant building blocks ratio. Solution self-assembly of such SCGMs resulted in well-defined 2D nanosheets with similar structural configurations, showing great tolerance in the number of building blocks. Subsequently, we proposed a “sandwiched-type” mode to illustrate the bilayer 2D supramolecular framework, in which crystalline blocks pack in head-to-head manner. In addition, sequence isomers provide an ideal platform to further verify that the thickness of 2D nanocrystal is linked with the tethering density determined by the number ratio of building blocks. We believe that this study could be a better complement to our previous work and then make us to be more in-depth understand the crystallization mechanism of SCGMs.

Objective: To develop a model combining clinical and radiomics features from CT scans for a preoperative noninvasive evaluation of Huvos grading of neoadjuvant chemotherapy in patients with HOS. Methods: 183 patients from center A and 42 from center B were categorized into training and validation sets. Features derived from radiomics were obtained from unenhanced CT scans.Following dimensionality reduction, the most optimal features were selected and utilized in creating a radiomics model through logistic regression analysis. Integrating clinical features, a composite clinical radiomics model was developed, and a nomogram was constructed. Predictive performance of the model was evaluated using ROC curves and calibration curves. Additionally, decision curve analysis was conducted to assess practical utility of nomogram in clinical settings. Results: LASSO LR analysis was performed, and finally, three selected image omics features were obtained.Radiomics model yielded AUC values with a good diagnostic effect for both patient sets (AUCs: 0.69 and 0.68, respectively). Clinical models (including sex, age, pre-chemotherapy ALP and LDH levels, new lung metastases within 1 year after surgery, and incidence) performed well in terms of Huvos grade prediction, with an AUC of 0.74 for training set. The AUC for independent validation set stood at 0.70. Notably, the amalgamation of radiomics and clinical features exhibited commendable predictive prowess in training set, registering an AUC of 0.78. This robust performance was subsequently validated in the independent validation set, where the AUC remained high at 0.75. Calibration curves of nomogram showed that the predictions were in good agreement with actual observations. Conclusion: Combined model can be used for Huvos grading in patients with HOS after preoperative chemotherapy, which is helpful for adjuvant treatment decisions.

H1N1 influenza virus is a significant global public health concern. Monoclonal antibodies (mAbs) targeting specific viral proteins such as hemagglutinin (HA) have become an important therapeutic strategy, offering highly specific targeting to block viral transmission and infection. This study focused on the development of mAbs targeting HA of the A/Victoria/2570/2019 (H1N1pdm09, VIC-19) strain by utilizing hybridoma technology to produce two mAbs with high binding capacity. Notably, mAb 2B2 has demonstrated a strong affinity for HA proteins in recent H1N1 influenza vaccine strains. In vitro assessments showed that both mAbs exhibited broad-spectrum hemagglutination inhibition and potent neutralizing effects against various vaccine strains of H1N1pdm09 viruses. 2B2 was also effective in animal models, offering both preventive and therapeutic protection against infections caused by recent H1N1 strains, highlighting its potential for clinical application. By individually co-cultivating each of the aforementioned mAbs with the virus in chicken embryos, four amino acid substitution sites in HA (H138Q, G140R, A141E/V, and D187E) were identified in escape mutants, three in the antigenic site Ca2, and one in Sb. The identification of such mutations is pivotal, as it compels further investigation into how these alterations could undermine the binding efficacy and neutralization capacity of antibodies, thereby impacting the design and optimization of mAb therapies and influenza vaccines. This research highlights the necessity for continuous exploration into the dynamic interaction between viral evolution and antibody response, which is vital for the formulation of robust therapeutic and preventive strategies against influenza.

Asymmetric layout gate station projects are prevalent in gate station engineering. When multiple pump units operate within such projects, the inflow patterns of the pump devices at different stations exhibit significant variations. Notably, edge pump units often display adverse operating characteristics, including vibration. This study aims to elucidate the hydraulic behavior of edge pump units in asymmetric layout gate station projects using numerical simulation methods. We validate the reliability of our numerical calculations through physical model tests. Specifically, we investigate the flow pressure pulsation characteristics of the axial flow pump device within the edge pump unit under various switching schemes employed in the gate station project. The results show that pressure fluctuations in axial flow pump devices exhibit distinct time-frequency characteristics based on different flow rates. An increase in flow rate results in a sharp rise in pressure fluctuation amplitudes within the axial flow pump device of the edge pump unit. During symmetric operation, the peak pressure fluctuations of the axial flow pump device are significantly smaller than those observed during asymmetric operation. This suggests that the edge pump unit operates more stably and experiences fewer pressure fluctuations under symmetric conditions. Optimizing the operation of edge pump units ensures stability and prolongs the service life of gate station projects.

The interior of a high-voltage cable causes a state of extrusion due to thermomechanical effects; the resulting stress and deformation can easily lead to the destruction of the cable structure. Aiming at the problem, we establish an electromagnetic–thermal–force field model of a high voltage cable. By considering the influence of temperature on the material properties, a bidirectional couple simulation of electromagnetic and thermal fields is established. The thermal load excitation is introduced into the structural field, and the simulation calculation of thermal strain and thermal stress of the axial and radial layers is realized. The influence of ambient temperature, load current, and circulating current defect factors on the thermal–force characteristics of each layer of the cable is studied. The results show that the response of the insulating layer to the thermomechanical effect is the most significant, and its characteristic change law shows the nonlinear trend. In addition, the thermal strain of the cable has an approximate axial symmetry; the axial thermomechanical effect is significantly higher than the radial direction. The maximum axial and radial deformations of the cable when running at full load are 1.21 and 0.16 mm respectively. Among the three influencing factors, the impact of circulating current defects on the thermomechanical effect of cables is the most obvious. The thermomechanical effect of the cable approximately is positively related to the square of the circulating current defect factors, the load current, and the ambient temperature.

ContextFew studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing’s syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear.ObjectiveTo compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function.MethodsWe prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment.ResultsPatients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P

The epiphytic bacteria in aquatic ecosystems, inhabiting a unique ecological niche with significant ecological function, have long been the subject of attention. Habitat characteristics and plant species are believed to be important in controlling the assembly of epiphytic bacteria. However, the underlying principle governing the assembly of the epiphytic bacterial community on macrophytes is far from clear. In this study, we systematically compared the diversity and community composition of epiphytic bacteria both in different habitats and on different species of macrophytes where they were attached. Results suggested that neither the plant species nor the habitat had a significant effect on the diversity and community of epiphytic bacteria independently, indicating that the epiphytic bacterial community composition was correlated to both geographical distance and individual species of macrophytes. Furthermore, almost all of the abundant taxa were shared between different lake regions or macrophyte species, and the most abundant bacteria belonged to Proteobacteria and Firmicutes. Our results demonstrated that the competitive lottery model may explain the pattern of epiphytic bacterial colonization of submerged macrophyte surfaces. This research could provide a new perspective for exploring plant–microbe interaction in aquatic systems and new evidence for the lottery model as the mechanism best explaining the assembly of epiphytic bacteria.

IntroductionHerpes simplex keratitis (HSK) is a blinding disease caused by corneal infection of Herpes simplex virus type 1 (HSV-1). Effective clearance of HSV-1 from the infected cornea is crucial for HSK management. Macrophages play an important part in the innate immune defense against viral infections. This study investigates the immunomodulatory role of NLRP12 in macrophage immune response during HSV-1 infection.MethodsNLRP12 expression post-infection was assessed in various macrophage cell lines. Overexpression of NLRP12 was achieved by lentiviral transfection, and its effect on HSV-1 replication and immune responses were examined. Mechanistic insights into the role of NLRP12 were explored using immunofluorescence and Western Blot. For in vivo studies, ocular adoptive transfer of NLRP12-overexpressing bone marrow derived macrophages (BMDMs) was performed. HSV-1 viral loads, HSK symptoms, and macrophage-mediated immune responses were investigated.ResultsA significant decrease in NLRP12 expression post-infection was observed in various macrophage cell lines. Overexpression of NLRP12 in macrophages reduced HSV-1 replication. Mechanistically, overexpression of NLRP12 triggered early and robust pyroptosis in response to HSV-1 infection, inducing interleukin (IL)-18 production and activating downstream antiviral responses through the JAK-STAT signaling pathway. In vivo, ocular adoptive transfer of NLRP12-overexpressing BMDMs to mouse corneas alleviated HSK damage and reduced HSV-1 viral loads. NLRP12-overexpressing BMDMs improved antiviral responses in the cornea and promoted the maturation of corneal-infiltrating macrophages and dendritic cells. Additionally, NLRP12-overexpressing BMDMs amplified the adaptive immune response in the submandibular draining lymph nodes.DiscussionThese findings highlight the role of NLRP12 in macrophage-mediated immune response against HSV-1 infection and suggest its potential for possible immunotherapy for HSK.

BackgroundThe relationship between hemorrhagic transformation (HT) and uric acid (UA) remains controversial. This study aimed to investigate the relationship between UA concentrations and the risk of HT following acute ischemic stroke (AIS).MethodsElectronic databases were searched for studies on HT and UA from inception to October 31, 2023. Two researchers independently reviewed the studies for inclusion. STATA Software 16.0 was used to compute the standardized mean difference (SMD) and 95% confidence interval (CI) for the pooled and post-outlier outcomes. Heterogeneity was evaluated using the I2 statistic and the Galbraith plot. Additionally, sensitivity analysis was performed. Lastly, Begg’s funnel plot and Egger’s test were used to assess publication bias.ResultsA total of 11 studies involving 4,608 patients were included in the meta-analysis. The pooled SMD forest plot (SMD = −0.313, 95% CI = −0.586–−0.039, p = 0.025) displayed that low UA concentrations were linked to a higher risk of HT in post-AIS patients. However, heterogeneity (I2 = 89.8%, p

ABSTRACT Gut microbiota of the bumblebee is critical as it modulates the health and fitness of the host. However, the mechanisms underlying the formation and maintenance of the diversity of bumblebee gut bacteria over a long period of evolution have yet to be elucidated. In particular, the gut bacterial diversity and community assembly processes of Bombus pyrosoma across the Chinese border remain unclear. In this study, we systematically carried out unprecedented sampling of 513 workers of the species Bombus pyrosoma across the Chinese landscape and used full-length 16S rRNA gene sequencing to examine their gut microbiota diversity and biogeography. The gut microbiota composition and community structure of Bombus pyrosoma from different geographical locations were diverse. On the whole, the gut bacteria Gilliamella and Snodgrassella are dominant in bumblebees, but opportunistic pathogens Serratia and Pseudomonas are dominant in some sampling sites such as Hb15, Gs1, Gs45, Qhs15, and Ssx35. All or part of environmental factors such as latitude, annual mean temperature, elevation, human footprint, population density, and annual precipitation can affect the alpha diversity and community structure of gut bacteria. Further analysis showed that the assembly and shift of bumblebee gut bacterial communities under geographical variation were mainly driven by the stochastic drift of the neutral process rather than by variable selection of niche differentiation. In conclusion, our unprecedented sampling uncovers bumblebee gut microbiome diversity and shifts over evolutionary time.IMPORTANCEThe microbiotas associated with organisms facilitates host health and fitness, and the homeostasis status of gut microbiota also reflects the habitat security faced by the host. In addition, managing gut microbiota is important to improve bumblebee health by understanding the ecological process of the gut microbiome. Thus, we first carried out an runprecedented sampling of 513 workers of the species Bombus pyrosoma across the Chinese landscape and used full-length 16S rRNA gene sequencing to uncover their gut microbiota diversity and biogeography. Our study provides new insights into the understanding of gut microbiome diversity and shifts for Chinese Bumblebee over evolutionary time.

ObjectiveTo investigate the diagnostic efficacy of the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model based on ultrasonographic radiomics for the differentiation of small clear cell Renal Cell Carcinoma (ccRCC) and Renal Angiomyolipoma (RAML).MethodsThe clinical, ultrasound, and contrast-enhanced CT(CECT) imaging data of 302 small renal tumors (maximum diameter ≤ 4cm) patients in Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2022 were retrospectively analyzed, with 182 patients of ccRCC and 120 patients of RAML. The ultrasound images of the largest diameter of renal tumors were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from ROI segmented images. The patients were randomly divided into training and internal validation cohorts in the ratio of 7:3. The Random Forest algorithm of the Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model. The efficacy of the prediction models was verified in an independent external validation cohort consisting of 69 patients, from 230 small renal tumor patients in two different institutions. The Delong test compared the predictive ability of three models and CECT. Calibration Curve and clinical Decision Curve Analysis were applied to evaluate the model and determine the net benefit to patients.Results491 ultrasonographic radiomics features were extracted from 302 small renal tumor patients, and 9 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. In the internal validation cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy of the clinical ultrasound imaging model, ultrasonographic radiomics model, comprehensive model, and CECT were 0.75, 76.7%, 60.0%, 70.0%; 0.80, 85.6%, 61.7%, 76.0%; 0.88, 90.6%, 76.7%, 85.0% and 0.90, 92.6%, 88.9%, 91.1%, respectively. In the external validation cohort, AUC, sensitivity, specificity, and accuracy of the three models and CECT were 0.73, 67.5%, 69.1%, 68.3%; 0.89, 86.7%, 80.0%, 83.5%; 0.90, 85.0%, 85.5%, 85.2% and 0.91, 94.6%, 88.3%, 91.3%, respectively. The DeLong test showed no significant difference between the clinical ultrasound imaging model and the ultrasonographic radiomics model (Z=-1.287, P=0.198). The comprehensive model showed superior diagnostic performance than the ultrasonographic radiomics model (Z=4. 394, P

Abstract The use of trastuzumab emtansine (T‐DM1) has revealed significant efficacy in HER2‐positive metastatic breast cancer (MBC). However, optimal therapeutic strategies following T‐DM1 failure remain a subject of debate in clinical practice. In this multicenter, retrospective, real‐world study, we sought to examine the effectiveness and safety of tyrosine kinase inhibitors (TKIs) as a therapeutic strategy in HER2‐positive MBC who developed T‐DM1 resistance. Between September 2018 and December 2022, 66 patients were enrolled. The median progression‐free survival of TKIs‐based therapy was 10.1 months (95% CI, 4.7–15.6). Objective response rate and clinical benefit rate were 18.2 and 66.7%, respectively. TKIs‐based therapy demonstrated better effectiveness in patients who had previously derived benefit from T‐DM1 and featured acquired resistance to trastuzumab. The most common adverse events were diarrhea (36, 54.5%), hand‐foot syndrome (31, 47.0%), and leucopenia (30, 45.5%). In conclusion, TKIs‐based therapy showed promising effectiveness and safety in HER2‐positive MBC patients after T‐DM1 failure.

Background Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment.Methods The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer.Results A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group.Conclusions High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment.

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.