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Αbstract In Parkinson’s disease (PD), Lewy pathology deposits in the cerebral cortex, but how the pathology disrupts cortical circuit integrity and function remains poorly understood. To begin to address this question, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. We reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern. Specifically, αSyn aggregates-bearing intratelencephalic neurons (ITNs) showed hyperexcitability, increased input resistance, and decreased cell capacitance, which were associated with impaired HCN channel function. Morphologically, the αSyn aggregates-bearing ITNs showed shrinkage of cell bodies and loss of dendritic spines. Last, we showed that partial dopamine depletion is not sufficient to alter thalamocortical transmission to cortical pyramidal neurons. Our results provide a novel mechanistic understanding of cortical circuit dysfunction in PD.

Abstract Objectives Ischaemic stroke (IS) has become a major health problem globally as it is one of the leading causes of long-term disability and death. This study aimed to evaluate the association between red cell distribution width (RDW) to lymphocyte (LYM) ratio (RLR) and 30-day mortality risk in patients with IS. Methods The present study employed a retrospectively cohort study design with the adult data extracted from the Medical Information Mart for Intensive Care (MIMIC-III, MIMIC-IV) databases between 2001 and 2019. The RLR was measured using RDW and LYM. Confounders were adjusted in Cox proportional hazards model. The outcome was 30-day mortality. Univariable and multivariable Cox proportional hazards models were establised. A further analysis was conducted on the basis of subgroup stratification by heart failure (HF) (yes or no), atrial fibrillation or flutter (yes or no), hypertension (yes or no), dyslipidemia (yes or no), sepsis (yes or no), and age (≥ 65 years and

BackgroundFibroblasts in the fibrotic heart exhibit a heterogeneous biological behavior. The specific subsets of fibroblasts that contribute to progressive cardiac fibrosis remain unrevealed. Our aim is to identify the heart fibroblast (FB) subsets that most significantly promote fibrosis and the related critical genes as biomarkers for ischemic heart disease.MethodsThe single nuclei RNA sequencing (snRNA-seq) and bulk RNA sequencing datasets used in this study were obtained from the Gene Expression Omnibus (GEO). The activity of gene sets related to progressive fibrosis was quantified for each FB cluster using the AddmoleculeScore function. Differentially expressed genes (DEGs) for the specific cell cluster with the highest fibrotic transcription dynamics were identified and integrated with bulk RNA sequencing data for analysis. Multiple machine learning models were employed to identify the optimal gene panel for diagnosing ischemic heart disease (IHD) based on the intersected DEGs. The effectiveness and robustness of the gene-derived diagnostic tool were validated using two independent IHD cohorts.Subsequently, we validated the signature genes using a rat post-myocardial infarction heart failure model.ResultsWe conducted an analysis on high-quality snRNA-seq data obtained from 3 IHD and 4 cardiac sarcoidosis heart samples, resulting in the identification of 16 FB clusters. Cluster2 exhibited the highest gene activity in terms of fibrosis-related transcriptome dynamics. The characteristic gene expression profile of this FB subset indicated a specific upregulation of COL1A1 and several pro-fibrotic factors, including CCDC102B, GUCY1A3, TEX41, NREP, TCAP, and WISP, while showing a downregulation of NR4A1, an endogenous inhibitor of the TGF-β pathway. Consequently, we designated this subgroup as COL1A1hiNR4A1low FB. Gene set enrichment analysis (GSEA) shows that the gene expression pattern of COL1A1hiNR4A1low FB was closer to pathways associated with cardiac fibrosis. Through machine learning, ten feature genes from COL1A1hiNR4A1low FB were selected to construct a diagnostic tool for IHD. The robustness of this new tool was validated using an independent cohort and heart failure rats.ConclusionCOL1A1hiNR4A1low FB possess heightened capability in promoting cardiac fibrosis. Additionally, it offers molecular insights into the mechanisms underlying the regulation of the TGF-β pathway. Furthermore, the characteristic genes of COL1A1hiNR4A1 FB could serve as valuable tools for diagnosing of IHD.

Objective(s): Bevacizumab is a commonly used anticancer drug in clinical practice, but it often leads to adverse reactions such as vascular endothelial damage, hypertension, arterial and venous thrombosis, and bleeding. This study investigated the protective effects of metformin against bevacizumab-induced vascular injury in a mouse model and examined the possible involvement of GDF15/PI3K/AKT/FOXO/PPARγ signaling in the effects.Materials and Methods: C57 male mice were purchased. To investigate metformin, the mice were assigned to the saline, bevacizumab (15 mg every 3 days), metformin (1200 mg/day), and bevacizumab+metformin groups. To investigate GDF15, the mice were assigned to the siNC+bevacizumab, siNC+bevacizumab+metformin, siGDF15+bevacizumab, and siGDF15+bevacizumab+metformin groups. Histological staining was used to evaluate vascular injury. Flow cytometry was used to evaluate apoptosis. ELISA was used to measure plasma endothelial injury markers and proinflammatory cytokines. qRT-PCR and western blot were used to determine the expression of GDF15 and PI3K/AKT/FOXO/PPARγ in aortic tissues.Results: Metformin alleviated bevacizumab-induced abdominal aortic injury, endothelial cell apoptosis, and systemic inflammation in mice (all P

Background: p97 (also known as valosin-containing protein, VCP) is a member of the AAA+ ATPase family and is intimately associated with protein quality control and homeostasis regulation. Therefore, pharmaceutical inhibition of p97 has been actively pursued as an anticancer strategy. Recently, p97 has emerged as an important pro-viral host factor and p97 inhibitors are being evaluated as potential antiviral agents. Methods: We designed and synthesized novel p97 inhibitors based on the rearrangement of the central fused ring of our previously reported p97 inhibitors. These compounds were tested for inhibition of p97, cytotoxicity, and antiviral activity against SARS-CoV-2. Molecular docking was also performed on selected inhibitors to shed light on their binding modes. Results: Among these new p97 inhibitors, two compounds possess enhanced anti-p97 activity over their parent compounds. More significantly, these two inhibitors exhibit strong antiviral activity against SARS-CoV-2 at doses with no significant cytotoxicity. Molecular docking reveals no major change of the binding mode relative to that of their parent compounds, further supporting our design strategy. Conclusions: These compounds are structurally novel p97 inhibitors that display low toxicity and possess promising antiviral activity against SARS-CoV-2 and potentially other viruses. Further structural exploration is therefore justified and improved analogs will serve as useful tools for studying p97 as a promising host antiviral target.

The colorimetric method, due to its rapid and low-cost characteristics, demonstrates a wide range of application prospects in on-site water quality testing. Current research on colorimetric detection using deep learning algorithms predominantly focuses on single-target classification. To address this limitation, we propose a multi-task water quality colorimetric detection method based on YOLOv8n, leveraging deep learning techniques to achieve a fully automated process of “image input and result output”. Initially, we constructed a dataset that encompasses colorimetric sensor data under varying lighting conditions to enhance model generalization. Subsequently, to effectively improve detection accuracy while reducing model parameters and computational load, we implemented several improvements to the deep learning algorithm, including the MGFF (Multi-Scale Grouped Feature Fusion) module, the LSKA-SPPF (Large Separable Kernel Attention-Spatial Pyramid Pooling-Fast) module, and the GNDCDH (Group Norm Detail Convolution Detection Head). Experimental results demonstrate that the optimized deep learning algorithm excels in precision (96.4%), recall (96.2%), and mAP50 (98.3), significantly outperforming other mainstream models. Furthermore, compared to YOLOv8n, the parameter count and computational load were reduced by 25.8% and 25.6%, respectively. Additionally, precision improved by 2.8%, recall increased by 3.5%, mAP50 enhanced by 2%, and mAP95 rose by 1.9%. These results affirm the substantial potential of our proposed method for rapid on-site water quality detection, offering new technological insights for future water quality monitoring.

In order to solve the problems of serious deterioration of braking efficiency of traditional eddy current retarder (ECR) in continuous operation and poor braking characteristics of hydraulic retarder (HR) at low speed, a novel four salient poles liquid-cooled electromagnetic retarder (FSP-LER) is proposed. The downhill dynamics model of medium and heavy vehicles is established to analyze the braking demand, the FSP-LER is designed according to the braking demand, and its braking characteristics are predicted by the equivalent magnetic circuit (EMC) method and the finite element method. Hierarchical variable domain fuzzy control strategy combined with retarder is utilized for braking control, and MATLAB is used to establish the controller and the long downhill braking model of the whole vehicle and perform joint simulation. The actual braking characteristics of the retarder prototype were tested by bench test and vehicle road test, and the results showed that the braking torque of the FSP-LER decreased by only 13.49% for 10 min of continuous operation, and the braking efficiency was still maintained by about 86% at a low speed of 500 r/min. The average error between the actual measured value of braking torque and the analyzed calculated value is less than 5%, and the braking torque can reach 2213 N $\cdot $ m when the rotational speed is 1250 r/min, which meets the braking demand of medium and heavy vehicles.

Phosphorus (P) and potassium (K) stress significantly affect the growth, physiological characteristics, and nutrient uptake of rice plants. This study investigated the photosynthetic nitrogen (N) metabolism, N uptake, and N utilization of plants under varied P and K supplies. Two local conventional high-yield rice varieties (Shennong 265 and Liaojing 294) were used. These varieties were subjected to the following hydroponic experimental treatments: HPHK (normal P and K concentrations), HPLK (normal P and 1/20 normal K concentration), LPHK (normal K and 1/20 normal P concentration), and LPLK (1/20 normal P and K concentrations). The results showed that the mesophyll cells had a relatively complete nuclear and chloroplast structures, and the antioxidant enzymes of the plants were significantly reduced under the HPHK treatment. Compared to the LP treatments (LPHK and LPLK), the HPHK treatment was found to have the following potential effects: effectively optimize plant configuration; promote leaf development (Pn, E, Ci, and Tr, chlorophyll, and leaf area index); significantly increase the N-metabolism-related enzyme activity of leaves and roots and the accumulation of N in the plant in the main growth stages; and significantly increase the rice yield and N-related efficiency. In conclusion, the HPHK treatment was found to be beneficial in improving the plant configuration, promoting photosynthetic N metabolism, and increasing grain yield and N-related utilization efficiency.

Abstract SARS-CoV-2 infection causes spike-dependent fusion of infected cells with ACE2 positive neighboring cells, generating multi-nuclear syncytia that are often associated with severe COVID. To better elucidate the mechanism of spike-induced syncytium formation, we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical stimulator for spike-induced cell-cell fusion. We show that HS binds spike and promotes spike-induced ACE2 clustering, forming synapse-like cell-cell contacts that facilitate fusion pore formation between ACE2-expresing and spike-transfected human cells. Chemical or genetic inhibition of HS mitigates ACE2 clustering, and thus, syncytium formation, whereas in a cell-free system comprising purified HS and lipid-anchored ACE2, HS stimulates ACE2 clustering directly in the presence of spike. Furthermore, HS-stimulated syncytium formation and receptor clustering require a conserved ACE2 linker distal from the spike-binding site. Importantly, the cell fusion-boosting function of HS can be targeted by an investigational HS-binding drug, which reduces syncytium formation in vitro and viral infection in mice. Thus, HS, as a host factor exploited by SARS-CoV-2 to facilitate receptor clustering and a stimulator of infection-associated syncytium formation, may be a promising therapeutic target for severe COVID.

Abstract Allogeneic tumor cell vaccines provide off‐the‐shelf convenience but lack patient specificity due to heterogeneity in tumor antigens. Here, allogeneic tumor cell corpses are converted into “zombie cells” capable of assimilating heterogeneous tumor by seizing cancer cells and spreading adjuvant infection. This causes pseudo‐oncolysis of tumors, transforming them into immunogenic targets for enhanced phagocytosis. It is shown that in postoperative tumor models, localized delivery of premade “zombie cells” through stepwise gelation in resection cavity consolidates tumor surgery. Compared to analogous vaccines lacking “seizing” or “assimilating” capability, “zombie cell” platform effectively mobilizes T cell response against residual tumors, and establishes immunological memory against tumor re‐challenge, showing less susceptibility to immune evasion. Despite using allogeneic sources, “zombie cell” platform functions as generalizable framework to produce long‐term antitumor immunity in different tumor models, showing comparable effect to autologous vaccine. Together, with the potential of off‐the‐shelf availability and personalized relevance to heterogenous tumor antigens, this study suggests an alternative strategy for timely therapy after tumor surgery.

Fibula transplantation plays an irreplaceable role in restoring the function and morphology of the defected mandible. However, the complex load-bearing environment of the mandible makes it urgent to accurately reconstruct the mandible, ensure the position of the condyle after surgery, and restore the patient’s occlusal function and contour. The intervention of digital design and three-dimensional (3D) printed titanium mesh provides a more efficient method and idea to solve this problem. Digital design guides the accurate positioning, osteotomy, and simultaneous implant placement during surgery, and 3D printed titanium mesh ensures stable condyle position after surgery, restoring good mandibular function. The double-layer folded fibula maintains the vertical height of the mandible and a good facial contour, and simultaneous implant placement can establish a good occlusal relationship. This study conducted a retrospective analysis of five patients with jaw defects who underwent digital fibula reconstruction over the past 3 years. It was found that the surgical protocol combining digital design, 3D printed intraoperative guides, 3D printed titanium mesh, free fibula flap, immediate implant, and occlusal reconstruction to repair jaw defects had more ideal facial appearance and biological function. It will provide a more reliable surgical protocol for clinical management of large mandibular defects.

The purpose of this paper is to investigate the effects of political connections on the association between firms' business strategy and their tax aggressiveness in an emerging economy such as China. The authors study a large sample of Chinese public firms from 2011 to 2017 using a panel regression model. In addition, a change analysis, an instrument variable test and alternative measures/samples are implemented as robustness tests. Firms adopting innovative business strategy are more tax aggressive overall. However, innovative firms with political connections are less tax aggressive compared to those without political connections. This paper contributes to the understanding of firms' tax behaviors in an emerging economy setting. It suggests that there are costs associated with political connections, such as foregone tax saving opportunities, which are understudies in the prior literature.

Northeast China is an important commercial grain base for China, but also the largest japonica rice production area. However, N, and K fertilizer application and unreasonable application times are prominent contradictions that restrict the development of japonica rice. This study aimed to investigate how to rationally apply N and K fertilizers to affect grain filling and ultimately increase the quality of the rice. In this field study, two N application levels and three K application ratios were set in 2020 and 2021 using Shennong 265 (SN265) and Meifengdao 61 (MF61). We found that the final seed growth and filling rate of SN265 were higher than those of MF61, and their filling characteristics were slow in the early stage and fast in the later stage, with large fluctuations. Appropriate reductions and increases of N and K fertilizer applications, respectively, in the early stage could improve grain filling. Compared with SN265, MF61 had a 3.2% increase in head rice rate, lower amylose and protein content, a decrease of chalkiness degree and chalkiness percentage by 23.96 and 34.00%, respectively, and more reasonable protein components. With the N application increase, the processing quality improved, the amylose and protein content and chalkiness increased, the protein components increased except for the milled rice glutelin, and the rice taste value decreased. At low N levels, increasing the proportion of K application was consistent with the effect of increasing N. The taste value of SN265 decreased linearly with the increase in the ratio of N application to pre-application of K, the highest taste value was obtained when the N fertilizer was applied at a rate of 180 kg ha−1, and the ratio of before and after K fertilizer application was about 1:2. The taste value of MF61 decreased linearly with the N application increase and showed a trend of increasing and then decreasing with the K application increase in the early stage. The taste peak gradually shifted back with the N application increase, and the highest taste value was obtained when N fertilizer was applied at 180 kg ha−1; the ratio of before and after K fertilizer application was about 3:2. By constructing the grain-filling quality evaluation system, the characteristic parameters of superior and inferior grains at the early and late stages of grain filling, respectively, greatly affected the rice taste value. Additionally, the percentage of the rice grain weight at the maximum grain-filling rate to the final rice grain weight (I) of superior grains, glutelin content, and value of the RVA profile characteristics were all critical reference indicators for rice taste quality.

The rapid development of hydrogen energy requires the use of natural gas infrastructure for hydrogen transportation. It is very important to study hydrogen-added natural gas transportation technology, which is a key way to rapidly develop coal-based gas and renewable energy. This study aims to study the influence of X80 pipeline steel's fatigue performance in hydrogen environment, and perform fatigue tests on notched round rod specimens under different hydrogen concentration. The experimental results show that hydrogen seriously affects the fatigue life of pipeline steel. After reaching a certain hydrogen concentration, as the hydrogen concentration continues to increase, the fatigue life decreases gradually. Combined with SEM analysis of fracture morphology, the decrease in the size and density of the dimples reduces the displacement amplitude, while the increase in the planar area increases the displacement during fatigue fracture due to accelerated crack propagation. From this study, we can know the influence of hydrogen concentration on the fracture morphology of pipeline steel, which provides an understanding of the effect of hydrogen on fatigue fracture morphology and a broader safety analysis.

Abstract Strategies that induce dysfunction in the endoplasmic reticulum (ER) hold great promise for anticancer therapy, but remain unsatisfactory due to the compensatory autophagy induction after ER disruption. Moreover, as autophagy can either promote or suppress cell survival, which direction of autophagy better suits ER‐targeting therapy remains controversial. Here, a targeted nanosystem is constructed, which efficiently escorts anticancer therapeutics into the ER, triggering substantial ER stress and autophagy. Concurrently, an autophagy enhancer or inhibitor is combined into the same nanoparticle, and their impacts on ER‐related activities are compared. In the orthotopic breast cancer mouse model, the autophagy enhancer increases the antimetastasis effect of ER‐targeting therapy and suppresses over 90% of cancer metastasis, while the autophagy inhibitor has a bare effect. Mechanism studies reveal that further enhancing autophagy accelerates central protein snail family transcriptional repressor 1 (SNAI1) degradation, suppressing downstream epithelial–mesenchymal transition, while inhibiting autophagy does the opposite. With the same trend, ER‐targeting therapy combined with an autophagy enhancer provokes stronger immune response and tumor inhibition than the autophagy inhibitor. Mechanism studies reveal that the autophagy enhancer elevates Ca2+ release from the ER and functions as a cascade amplifier of ER dysfunction, which accelerates Ca2+ release, resulting in immunogenic cell death (ICD) induction and eventually triggering immune responses. Together, ER‐targeting therapy benefits from the autophagy‐enhancing strategy more than the autophagy‐inhibiting strategy for antitumor and antimetastasis treatment.

SIRT2 is a member of NAD+-dependent sirtuins and its inhibition has been proposed as a promising therapeutic approach for treating human diseases, including neurodegenerative diseases, cancer, and infections. Expanding SIRT2 inhibitors based on the 3-aminobenzyloxy nicotinamide core structure, we have synthesized and evaluated constrained analogs and selected stereoisomers. Our structure-activity relationship (SAR) study has revealed that 2,3-constrained (S)-isomers possess enhanced in vitro enzymatic inhibitory activity against SIRT2 and retain excellent selectivity over SIRT1 and SIRT3, provided that a suitable ring A is used. This current study further explores SIRT2 inhibitors based on the 3-aminobenzyloxy nicotinamide scaffold and contributes to the discovery of potent, selective SIRT2 inhibitors that have been actively pursued for their potential therapeutic applications.

Abstract Proper sealing of laryngeal mask airways (LMAs) is critical for airway management in clinical use. Understanding the sealing mechanism can significantly help front-line anaesthetists to reduce the incidence of adverse events. However, anaesthetists, who may not have the most substantial engineering backgrounds, lack intuitive ways to develop an understanding of the LMA sealing mechanism effectively. The paper aims to study the LMA-pharynx sealing mechanisms from the perspective of front-line anaesthetists. We use a computer-aided 3D modelling technique to visualise the LMA—pharynx interactions, which helps anaesthetists identify the critical areas of complications. Furthermore, we conduct a quantitative pressure distribution analysis of the LMA-pharynx contacting surface using the finite element analysis technique, which helps further understand the sealing mechanics in those areas. We present two cases studies based on one male volunteer, aged 50, inserted with a ProSeal LMA. In the first case, a relatively low cuff pressure (CP) was applied to simulate the clinical circumstances in which complications related to air leakage are most likely to happen; in the second case, we increase the CP to a relatively high value to simulate the scenarios with an increased risk of complications related to high mucosal pressure. The experiments suggest the follows: (1) Sore throat complications related to high mucosal pressure is most likely to occur in the hypopharynx with a high CP setting, particularly in the areas where the cricoid cartilage presses the mucosa. (2) The narrow hyoid bone super horn width likely causes LMA insertion difficulties. (3) Insufficient CP will significantly increase the risk of air leakage in the oropharynx. A complete sealing pressure line in the contacting surface will be formed with sufficient CP, thereby preventing the air leakage into the oral.

This study conducts objective circulation classifications of rainstorm days associated with Northeast China Cold Vortexes (NECVs) in the northeast of China (NEC) during the warm seasons (May–September). To determine the optimal method and number of types, the performances of ten objective circulation classification methods are first evaluated by several evaluation indexes. Self-Organizing Maps method is then used as the optimal method to classify rainstorms into five types. The results show that the different synoptic circulation patterns are accompanied by distinctive large-scale circulation backgrounds, precipitation characteristics, thermodynamic and moisture conditions. In type 1, the strong western Pacific subtropical high extends north to connect with the mid-latitude ridge in the east of the NEC, and a shallow trough lies in the west of the NEC. This configuration brings the most daily and hourly mean precipitation of all types. A low-pressure anomaly with an obvious trough controls the NEC in type 2, which has a higher frequency. In type 3, the low-pressure anomaly shrinks to the south of the NEC, and the NEC is controlled by the cut-off low vortex. Type 4 has the strongest hourly precipitation and features a meridional high-low-high pressure anomaly, and the narrow zonal low-pressure anomaly is in the NEC. Two low-pressure anomalies and a westerly trough can be found in type 5 and are distributed in a southwest-northeast orientation. These synoptic circulation patterns and the corresponding spatial distribution of rainstorm-day precipitation indicate that the objective circulation classification is effective in helping understand the large-scale circulation and precipitation characteristics associated with NECVs.

The ubiquitous presence of microplastics in aquatic environments is considered a global threat to aquatic organisms. Species of the genus Daphnia provide an important link between aquatic primary producers and consumers of higher trophic levels; furthermore, these organisms exhibit high sensitivity to various environmental pollutants. Hence, the biological effects of microplastics on Daphnia species are well documented. This paper reviews the latest research regarding the ecotoxicological effects of microplastics on Daphnia, including the: 1) responses of individual, population, and community attributes of Daphnia to microplastics; 2) influence of the physical and chemical properties of microplastics; and 3) joint toxicity of microplastics and other pollutants on responses of Daphnia. Our literature review found that the published literature does not provide sufficient evidence to reveal the risks of microplastics at the population and community levels. Furthermore, we emphasized that high-level analysis has more general implications for understanding how individual-level research can reveal the ecological hazards of microplastics on Daphnia. Based on this review, we suggest avenues for future research, including microplastic toxicology studies based on both omics-based and community-level methods, especially the latter.

BackgroundPatients with hepatocellular carcinoma are often affected by metastases, but condylar metastasis is particularly rare.Case presentationA 51-year-old man with a history of hepatocellular carcinoma requested treatment for facial pain. Computed tomography indicated that the condylar bone has been destroyed and fractured. Pathology confirmed condylar metastasis from hepatocellular carcinoma. Complete metastasectomy and condylar reconstruction were performed to preserve his facial appearance. No local recurrence or distant metastasis was found at 8 months of follow-up.ConclusionThe condyle can be a metastatic site of hepatocellular carcinoma, regardless of its rarity. Long-term comprehensive surveillance and follow-up are needed for patients with hepatocellular carcinoma. The presence of solitary mass does exclude the possibility of metastatic cancer for these patients, and postoperative imaging and pathological diagnosis are important to determine its origin. If patients’ physical condition permits, the mass can be completely excised, and the physiological function can be restored and reconstructed.

The airworthiness standards of the transport category airplanes stipulate that the high energy rotor equipment must be of the sufficient containment capacity. It is of great importance to study the containment and weight reduction for the air turbine starter. In this paper, based on an OSF design, Kriging response surface model and MOGA algorithm, a neck structure optimal design method was proposed for the air turbine wheel. Using the optimal design method, the optimal structural parameters were suggested as the design parameters, and verified by the over-speed burst test. The maximum errors of the burst speeds between the experimental and design values are less than 2%, and the neck structure turbine wheel breaks in the neck as expected, validating the accuracy of the optimal design method. Then, the effects of turbine wheel burst modes on the containment were investigated quantitatively, and verified by the containment tests. Based on the experimental and simulation results, the containment design method was proposed for the neck structure turbine wheel. The results show that compared with the trisection wheel burst, the rim burst dramatically decrease the mass and initial kinetic energy of burst released fragments by 63.3% and 24.8%, thereby greatly reducing the thickness and the mass of the containment ring by 29.5% and 29.1%.

Abstract Background Gastric cancer (GC), a common malignancy of the human digestive system, represents the second leading cause of cancer-related deaths worldwide. Early detection of GC has a significant impact on clinical outcomes. The aim of this study was to identify potential GC biomarkers. Methods In this study, we conducted a multi-step analysis of expression profiles in GC clinical samples downloaded from TCGA database to identify differentially expressed miRNAs (DEMs) and differentially expressed mRNAs (DEGs). Potential prognostic biomarkers from the available DEMs were then established using the Cox regression method. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological role of the predicted target genes of the miRNA biomarkers. Then, the prognostic DEM-mediated regulatory network was constructed based on transcription factor (TF)–miRNA–target interaction. Subsequently, the consensus genes were further determined based on the overlap between DEGs and these target genes of DEMs. Besides, expression profile, co-expression analysis, immunity, and prognostic values of these prognostic genes were also investigated to further explore the roles in the mechanism of GC tumorigenesis. Results We got five miRNAs, including miR-23b, miR-100, miR-143, miR-145, and miR-409, which are associated with the overall survival of GC patients. Subsequently, enrichment analysis of the target genes of the miRNA biomarkers shown that the GO biological process terms were mainly enriched in mRNA catabolic process, nuclear chromatin, and RNA binding. In addition, the KEGG pathways were significantly enriched in fatty acid metabolism, extracellular matrix (ECM) receptor interaction, and proteoglycans in cancer pathways. The transcriptional regulatory network consisting of 68 TFs, 4 DEMs, and 58 targets was constructed based on the interaction of TFs, miRNAs, and targets. The downstream gene ETS1 of miR-23b and TCF4 regulated by ETS1 were obtained by the regulatory network construction and co-expression analysis. High expression of ETS1 and TCF4 indicated poor prognosis in GC patients, particularly in the advanced stages. The expression of ETS1 and TCF4 was correlated with CD4+ T cells, CD8+ T cells, and B cells. Conclusions miR-23b, ETS1, and TCF4 were identified as the prognostic biomarkers. ETS1 and TCF4 had potential immune function in GC, which provided a theoretical basis for molecular-targeted combined immunotherapy in the future.

The traditional lateral flow immunoassay (LFIA) detection method suffers from issues such as unstable detection results and low quantitative accuracy. In this study, we propose a novel multi-test line lateral flow immunoassay quantitative detection method using smartphone-based SAA immunoassay strips. Following the utilization of image processing techniques to extract and analyze the pigments on the immunoassay strips, quantitative analysis of the detection results was conducted. Experimental setups with controlled lighting conditions in a dark box were designed to capture samples using smartphones with different specifications for analysis. The algorithm’s sensitivity and robustness were validated by introducing noise to the samples, and the detection performance on immunoassay strips using different algorithms was determined. The experimental results demonstrate that the proposed lateral flow immunoassay quantitative detection method based on image processing techniques achieves an accuracy rate of 94.23% on 260 samples, which is comparable to the traditional methods but with higher stability and lower algorithm complexity.

Abstract Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.

The presynaptic protein α-synuclein (αSyn) has been suggested to be involved in the pathogenesis of Parkinson’s disease (PD). In PD, the amygdala is prone to develop insoluble αSyn aggregates, and it has been suggested that circuit dysfunction involving the amygdala contributes to the psychiatric symptoms. Yet, how αSyn aggregates affect amygdala function is unknown. In this study, we examined αSyn in glutamatergic axon terminals and the impact of its aggregation on glutamatergic transmission in the basolateral amygdala (BLA). We found that αSyn is primarily present in the vesicular glutamate transporter 1-expressing (vGluT1+) terminals in the mouse BLA, which is consistent with higher levels of αSyn expression in vGluT1+ glutamatergic neurons in the cerebral cortex relative to the vGluT2+ glutamatergic neurons in the thalamus. We found that αSyn aggregation selectively decreased the cortico-BLA, but not the thalamo-BLA, transmission; and that cortico-BLA synapses displayed enhanced short-term depression upon repetitive stimulation. In addition, using confocal microscopy, we found that vGluT1+ axon terminals exhibited decreased levels of soluble αSyn, which suggests that lower levels of soluble αSyn might underlie the enhanced short-term depression of cortico-BLA synapses. In agreement with this idea, we found that cortico-BLA synaptic depression was also enhanced in αSyn knockout mice. In conclusion, both basal and dynamic cortico-BLA transmission were disrupted by abnormal aggregation of αSyn and these changes might be relevant to the perturbed cortical control of the amygdala that has been suggested to play a role in psychiatric symptoms in PD.

Porous bone scaffolds based on high-precision 3D printing technology gave recently been developed for use in bone defect repair. However, conventional scaffold materials have poor mechanical properties and low osteogenic activity, limiting their clinical use. In this study, a porous composite tissue-engineered bone scaffold was prepared using polylactic acid, nano-hydroxyapatite, and nano-magnesium oxide as raw materials for high-precision 3D printing. The composite scaffold takes full advantage of the personalized manufacturing features of 3D printers and can be used to repair complex bone defects in clinical settings. The composite scaffold combines the advantages of nano-hydroxyapatite, which improves the formability of scaffold printing, and of nano-magnesium oxide, which regulates pH during degradation and provide a good environment for cell growth. Additionally, nano-magnesium oxide and nano-hydroxyapatite have a bidirectional effect on promoting the compressive strength and osteogenic activity of the scaffolds. The prepared composite porous scaffolds based on 3D printing technology show promise for bone defect repair.

Malignancy, surgical resection, and neoadjuvant and/or adjuvant chemotherapy increase the low-extremity deep vein thrombosis (LDVT) risk in patients with breast cancer, bringing in great physical burdens, disabilities, and worse survivals. However, LDVT in surgical breast cancer patients is scarcely reported. Therefore, this study aimed to evaluate the incidence and related factors for LDVT in these patients. Patients with breast cancer who underwent surgical resection were included. LDVT was examined on the day of discharge and 1 month after the discharge. A total of 491 eligible patients were included, among which 11 (2.2%) patients occurred LDVT. Besides, higher age, history of diabetes mellitus, advanced T and tumor node metastasis (TNM) stages, higher platelet count, and shorter activated partial thromboplastin time (APTT) were correlated with increased LDVT incidence (all p < 0.05). Additionally, higher age [p = 0.004, odds ratio (OR) (95% CI): 1.082 (1.023–1.144)], history of diabetes mellitus [p = 0.003, OR (95% CI): 10.426 (2.219–48.986)], and a higher platelet count [p = 0.008, OR (95% CI): 1.017 (1.004–1.029)] were independent factors for increased LDVT incidence, while higher APTT [p = 0.004, OR (95% CI): 0.636 (0.467–0.866)] was an independent factor for decreased LDVT incidence. Lastly, the risk prediction model involving age, history of diabetes mellitus, platelet count, and APTT showed a good ability to predict LDVT occurrence (area under curve: 0.919, 95% CI: 0.869–0.968). In conclusion, the LDVT incidence is 2.2%, and its independent factors consist of age, history of diabetes mellitus, platelet count, and APTT in patients with breast cancer who underwent surgical resection, which provides evidence for the prevention and surveillance of LDVT in surgical breast cancer.

This study aims to explore the feasibility of the novel temperature-sensitive hydrogel-based dual sustained-release system (Van/SBA-15/CS-GP-SA) in the repair and treatment of infectious jaw defects. Van/SBA-15 was prepared using the mesoporous silica (SBA-15) as a carrier for vancomycin hydrochloride (Van), and Van/SBA-15 was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectrometry (EDS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR), Brunauer–Emmett–Teller (BET), and Barrett–Joyner–Halenda (BJH). The characterization results confirm that Van is loaded in SBA-15 successfully. Van/SBA-15/CS-GP-SA is constructed by encapsulating Van/SBA-15 in chitosan–sodium glycerophosphate–sodium alginate hydrogel (CS-GP-SA). The microstructures, sustained-release ability, biocompatibility, and antibacterial properties of Van/SBA-15/CS-GP-SA were systematically studied. Van/SBA-15/CS-GP-SA is found to have promising sustained-release ability, outstanding biocompatibility, and excellent antibacterial properties. This study provides new ideas for the management of infectious jaw defects.

To search for Zika virus (ZIKV) antivirals, we have further explored previously reported 7H-pyrrolo[2,3-d]pyrimidines by examining an alternative substitution pattern of their central scaffold, leading to compound 5 with low micromolar antiviral activity. To circumvent the synthetic difficulties associated with compound 5, we have exploited a 1H-pyrazolo[3,4-d]pyrimidine scaffold and performed structure-activity relationship studies on its peripheral rings A and B. While ring B is less sensitive to structural modifications, an electron-withdrawing group at the para position of ring A is preferred for enhanced antiviral activity. Overall, we have not only discovered an alternative substitution pattern centered on a 1H-pyrazolo[3,4-d]pyrimidine scaffold but also generated anti-ZIKV compounds including 6 and 13, which possess low micromolar antiviral activity and relatively low cytotoxicity. These compounds represent new chemotypes that will be further optimized in our continued efforts to discover anti-ZIKV agents.

Light, simple, and high-efficiency fertilization is currently an effective method used to improve quality and increase yield. Most research has only focused on the yield or quality of rice, and no effective or in-depth studies exist on the key stage of panicle, which is essential for these two aspects. This study aimed to determine the effect of applying Nitrogen (N) and Potassium (K) fertilizers on the yield and quality at different leaf ages. The rice cultivar, Shennong 265, was grown in the field-tube condition at the 5-leaf age with K fertilizer at different panicle stages. Five K fertilizer and four N fertilizer levels were applied simultaneously during two growing seasons in 2020–2021. The application of K fertilizer at different panicle stages significantly affected the yield and quality. The application of K and N fertilizers at the 12th-leaf-age increased the number of panicles and grains per panicle, thereby increasing the yield with an average increase of 23.20% over local farmer’s fertilization model (CK) in two years. Application at the 10th-leaf age reduced the starch and protein content of the rice and improved the nutritional quality and taste, with an average increase of 11.08 points compared to CK in two years. The processing quality was the best at the panicle K fertilizer application rate of 47.81–64.69 kg ha−1, and the starch and protein contents were the lowest at the panicle K fertilizer application rate of 56.25 kg ha−1. Under different panicle K fertilizer application rates, N fertilizers had great differences in processing quality but had slight differences in nutritional quality; that is, the starch and protein content (total protein and four protein components) significantly increased. The application of panicle N fertilizer mainly affected starch pasting viscosity (RVA profile characteristics). When panicle K fertilizer was applied after panicle N fertilizer, the yield and quality showed a trend of synergistic improvement. Although this improvement was a low-level synergy, it can still be a direction used to explore the synergistic improvement of output and quality.

Ridge tillage at two fertilizer depths is a new type of conservation tillage method that was previously shown to substantially improve rice yield. This study aimed to compare the effects of continuous ridge tillage at two fertilizer depths (L treatment) with those of conventional cultivation (P treatment) on bacterial and fungal diversity in the rice root zone and study the correlation between microorganisms and yield components. At the mature stage, the yield and yield components of rice plants were compared. Test soil (0–20 cm) with continuous tillage for 3 years was used for high-throughput sequencing to analyze the microbial community structure in the root–soil of the two treatments. We found that the L treatment increased soil nutrient content and improved soil physical properties, which altered the composition of the microbial community. The bacterial ACE and Chao indices in the L treatment increased by 1.46% and 1.83%, respectively, and the fungal ACE and Chao indices increased by 5.25% and 5.49%, compared with the P treatment, respectively. The average theoretical yield under the L treatment was 9781.51 kg/ha, which was 19.23% higher than that under the P treatment. Continuous ridge tillage at two fertilizer depths can provide a better soil environment for rice growth and increase the yield.

Rice yield is determined by source, sink, and flow and the coordination of these factors. However, the genetic base of the sink-flow is still unknown. We conducted on genome-wide association to detect quantitative trait loci (QTL) related to sink size (the number of rachis branches and spikelet number in rachis branches) and flow vascular bundle (large and small vascular bundles number in panicle neck and second internode) using 440 germplasm resources. The accessions exhibited marked variation in all traits and demonstrated complex phenotypic correlations. A total of 138 QTL affecting the 8 traits were detected using 3,188,500 high-quality single nucleotide polymorphism markers. Sixteen QTL clusters simultaneously affected flow and sink traits, which might explain the genetic base of significant correlations between flow and sink traits. The nine candidate genes in two consistent chromosomal regions simultaneously affecting multiple vascular bundle and sink size traits by performing gene-based association analysis and haplotype analysis. Among them, D2 (LOC_Os01g10040) and Gn1a (LOC_Os01g10110) for qPLVN1.1, qSLVN1.1, and qPRN1.2 and OsPIN5b (LOC_Os08g41720) for qPLVN8, qSLVN8, qSSVN8, and qSTSN8.2 were considered the most likely candidate genes based on functional annotations. The results provide useful information for improving rice yield potential via balancing sink–flow relationships by marker-assisted selection.

Rotor systems installed in a transportation system or under seismic excitations are considered to have a moving base. Although extensive research has been conducted on the dynamic behavior of the single-rotor system under base motions, few studies have dealt with the dynamics of dual-rotor systems, especially the counter-rotating dual-rotor systems used in airplane engines. Moreover, mass unbalance and gravity are unavoidable excitations for most rotor systems. Therefore, the vibration properties of a counter-rotating dual-rotor system with the coupled effects of base motions, mass unbalance and gravity are investigated in this paper for the first time. Using the Lagrange principle associated with the finite element method, a general model for dual-rotor systems under base motions was established by using Timoshenko beam elements, leading to a detailed analysis of the natural properties and harmonic responses of the system. The results revealed that different whirling modes (backward, forward or both) may be mutually excited. This research can be helpful for the design and vibration analysis of dual-rotor systems concerned with base motion.

An understanding of the leaf and root traits associated with high nitrogen (N) absorption and utilization is very important in the development of N-efficient varieties in crop breeding programs. However, in rice, the relations between these traits and nitrogen use efficiencies (NUEs) have yet to be identified. Therefore, the responses of leaf and root traits and yields of the three main japonica rice cultivars in northern China were examined at a range of N application rates. The rice cultivars, Shennong 265 (SN265), Tiejing 11 (TJ11), and Fengjing (FJ), were grown in the field at six N rates (0, 60, 120, 180, 240, and 300 kg ha−1) applied during two growing seasons (2018 and 2019). With the increase in N rate, the grain yield of SN265 and TJ11 increased, whereas the grain yield of FJ first increased and then decreased. The grain yield of FJ was higher than that of SN265 and TJ11 at lower N rates, whereas the grain yields of SN265 and TJ11 were higher than that of FJ at higher N rates. The NUEs decreased with the increase in N rates. At lower N rates, the ability of rice to obtain N was the main limitation on rice yield, but with the increase in N rates, the limitation on yield due to N absorption capacity gradually weakened. However, at higher N rates, rice yields were restricted by the ability to utilize N. Compared with TJ11 or FJ, SN265 had higher N utilization capacity primarily because of its higher Rubisco activity, NR activity, GS activity, and ROA. Compared with SN265 or TJ11, FJ had a higher N absorption capacity that was attributed to its larger root architecture, which might have also been one of the reasons for lower N utilization. Therefore, by improving N absorption and utilization-related leaf and root traits, high yields and NUEs can be achieved in rice production at different N application rates.

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

The article delves into the intricate changes occurring within the primary motor cortex (M1) in the context of Parkinson's disease (PD). It revolves around the central hypothesis that the degeneration of midbrain dopaminergic (DA) neurons, a hallmark of PD, triggers specific adaptations in M1 circuits. It further employs a range of multidisciplinary techniques, including optogenetics and electrophysiology.