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Abstract Background To evaluate the efficacy and safety of anlotinib combined with chemotherapy in the treatment of advanced soft tissue sarcoma (STS). Methods A total of 14 patients with advanced STS consisting of 4 liposarcoma, 3 undifferentiated polymorphous sarcoma, 2 synovial sarcoma, 1 Extraosseous ewing sarcoma, 1 spindle cell sarcoma, 1 Sarcomatoid malignant mesothelioma, 1 hemangiosarcoma, and 1 fibrosarcoma, were treated with anlotinib plus chemotherapy. The anlotinib was combined with chemotherapy as the first-line treatment in 13 patients, and as second-line treatment in 1 patient. Chemotherapy regimens were based on anthracyclines and ifosfamide, and other drugs included paclitaxel, and so on. Efficacy and safety were evaluated every 2 treatment cycles. Results According to the stage of AJCC, 9 patients were stage III and 5 patients were stage IV. The average cycle of treatment is 3.86. Among the 14 patients, 2 cases had received surgical treatment after neoadjuvant chemothrapy, 5 cases had partial response (PR), 7 cases had stable disease (SD), and 2 cases had progressive disease (PD). The overall response rate (ORR) was 35.7% (5/14). Patients who had not underwent surgical treatment were with a disease control rate (DCR) of 83.3% (10/12). The median progression free survival (PFS) was 8.25 months. The common treatment-related adverse effects included bone marrow suppression, nausea, vomiting and hypertension. Three patients had severe adverse effect, which was febrile neutropenia. No treatment-related death was found. Conclusions Anlotinib combined with chemotherapy in the treatment of STS is effective and tolerable, which is a promising strategy. It is worthy of further clinical research.

Abstract Background Pulmonary fibrosis is a serious interstitial lung disease with no viable treatment except for lung transplantation. Glucagon-like peptide-1 receptor (GLP-1R), commonly regarded as an antidiabetic target, exerts antifibrotic effects on various types of organ fibrosis. However, whether GLP-1R modulates the development and progression of pulmonary fibrosis remains unclear. In this study, we investigated the antifibrotic effect of GLP-1R using in vitro and in vivo models of pulmonary fibrosis. Methods A silica-induced pulmonary fibrosis mouse model was established to evaluate the protective effects of activating GLP-1R with liraglutide in vivo. Primary cultured lung fibroblasts treated with TGF-β1 combined with IL-1β (TGF-β1 + IL-1β) were used to explore the specific effects of liraglutide, MCC950, and 3PO on fibroblast activation in vitro. Cell metabolism assay was performed to determine the glycolytic rate and mitochondrial respiration. RNA sequencing was utilized to analyse the underlying molecular mechanisms by which liraglutide affects fibroblast activation. ChIP‒qPCR was used to evaluate histone lactylation at the promoters of profibrotic genes in TGF-β1 + IL-1β- or exogenous lactate-stimulated lung fibroblasts. Results Activating GLP-1R with liraglutide attenuated pulmonary inflammation and fibrosis in mice exposed to silica. Pharmacological inhibition of the NLRP3 inflammasome suppressed PFKFB3-driven glycolysis and vice versa, resulting in decreased lactate production in TGF-β1 + IL-1β-stimulated lung fibroblasts. Activating GLP-1R inhibited TGF-β1 + IL-1β-induced fibroblast activation by disrupting the interaction between the NLRP3 inflammasome and PFKFB3-driven glycolysis and subsequently prevented lactate-mediated histone lactylation to reduce pro-fibrotic gene expression. In addition, activating GLP-1R protected mitochondria against the TGF-β1 + IL-1β-induced increase in oxidative phosphorylation in fibroblasts. In exogenous lactate-treated lung fibroblasts, activating GLP-1R not only repressed NLRP3 inflammasome activation but also alleviated p300-mediated histone lactylation. Finally, GLP-1R activation blocked silica-treated macrophage-conditioned media-induced lung fibroblast activation. Conclusions The antifibrotic effects of GLP-1R activation on pulmonary fibrosis could be attributed to the inhibition of the interaction between NLRP3 inflammasome and PFKFB3-driven glycolysis, and histone lactylation in lung fibroblasts. Thus, GLP-1R is a specific therapeutic target for the treatment of pulmonary fibrosis.

Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract Effectively controlling the selective conversion of CO2 photoreduction to C2 products presents a significant challenge. Here, we develop a heterojunction photocatalyst by controllably implanting Au nanoparticles and single atoms into unsaturated Mo atoms of edge-rich MoS2, denoted as Aun/Au1-CMS. Photoreduction of CO2 results in the production of CH3COOH with a selectivity of 86.4%, which represents a 6.4-fold increase compared to samples lacking single atoms, and the overall selectivity for C2 products is 95.1%. Furthermore, the yield of CH3COOH is 22.4 times higher compared to samples containing single atoms and without nanoparticles. Optical experiments demonstrate that the single atoms domains can effectively capture photoexcited electrons by the Au nanoparticles, or the local electric field generated by the nanoparticles promotes the transfer of photogenerated electrons in MoS2 to Au single atoms, prolonging the relaxation time of photogenerated electrons. Mechanistic investigations reveal that the orbital coupling of Au5d and Mo4d strengthens the oxygen affinity of Mo and carbon affinity of Au. The hybridized orbitals reduce energy splitting levels of CO molecular orbitals, aiding C–C coupling. Moreover, the Mo−Au dual-site stabilize the crucial oxygen-associated intermediate *CH2CO, thereby enhancing the selectivity towards CH3COOH. The cross-scale heterojunctions provide an effective strategy to simultaneously address the kinetical and thermodynamical limitations of CO2-to-CH3COOH conversion.

The Rainfall thresholds are among the most commonly used criteria for predicting rainfall-induced landslides. However, existing empirical rainfall thresholds mainly focused on regional landslide warnings, lacking consideration for the spatial variability of rainfall thresholds for individual landslides within the region. This study uses historical rainfall-induced landslide data and hourly rainfall data from Bazhong City (2014 – 2021) to employ Kriging interpolation methods. It extracts four types of short-term rainfall (1 hour, 12 hours, 24 hours, 72 hours) and their corresponding long-term rainfall (7 days before the landslide occurrence). In these four threshold models, the distribution of long-term and short-term rainfall thresholds in each group is calculated and then validated using landslide disaster data from 2021. The research results indicate that the prediction accuracy of the four threshold models ranges from 40% to 65%, suggesting good potential for practical application. Additionally, the prediction accuracy improves with the increase in the duration of short-term rainfall. The prediction accuracy for rainfall thresholds calculated from the 72-hour-7-day model is highest, reaching 62%, while the 1-hour-7-day model achieves 46%. Based on the highest prediction accuracy of these models, the study calculates the optimal ratios for short-term and long-term disaster-causing rainfall for four types of models. This leads to a quantitative division between short-term rainfall-induced landslides and long-term rainfall-induced landslides. By calculating the spatial distribution of disaster-causing rainfall, the study extracts rainfall thresholds at potential landslide locations, achieving the goal of one threshold per site in the region and enhancing existing models for calculating rainfall thresholds.

Cancer microbiota have recently been demonstrated in several cancer types. The microbiome enhances inflammation in the cancer microenvironment and affects the disease pathology by regulating tumourigenesis, cancer progression, and chemotherapy resistance. Hepatoblastoma (HB), the most common childhood malignant tumour, is a malignant embryonic tumour. However, the pathogenesis and molecular basis of HB remain poorly understood. In this study, to explore the existence and distribution of the microbiome in tumour tissues and adjacent non-tumour tissues of children with HB, we mainly performed 16S rDNA sequencing, and the results showed that the diversity and abundance of the microbiome in children with HB were significantly different between HB tumours and adjacent non-tumour tissues (p

Background The model for end-stage liver disease (MELD) score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure (ACLF). In this study, we identified additional predictive parameters and reformed the MELD score to predict ACLF more accurately.Methods A meta-analysis was performed on relevant studies to identify the predictive factors of 28-day/90-day outcomes of ACLF, which were validated in two large prospective cohorts. A prognostic score was developed by incorporating predictive parameters into the MELD score. The model was evaluated with a focus on discrimination and calibration.Results The meta-analysis incorporated 32 cohort studies with a total of 13 939 patients, of which 13 risk factors were identified, and 3 risk factors (age, neutrophil count and hepatic encephalopathy (HE) grade) besides MELD score were validated in 751 patients with ACLF derived from two prospective cohorts. A new model (Chinese Acute-on-Chronic Liver Failure Consortium (CATCH-LIFE)-MELD score) was developed as follows: 0.028×age+0.3×HE grade+0.039×neutrophil count+0.079×MELD score. CATCH-LIFE-MELD score achieved a concordance index of 0.791/0.788 for 28-day/90-day outcomes, which is superior to other traditional scores. Other discrimination indices, including net reclassification improvement, integrated discrimination improvement and probability density function, and calibration including Nagelkerke’s R2 and Brier scores confirmed its superiority. Moreover, the accuracy of CATCH-LIFE-MELD score remained stable. It was highest in patients with or without hepatitis B virus infection, cirrhosis, liver failure or under the Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria or European Association for the Study of the Liver (EASL) criteria. All results were substantiated by an evaluation using an external cohort.Conclusions CATCH-LIFE-MELD score, a modified MELD score exhibited improved accuracy in predicting the short-term prognosis of ACLF than other traditional scores.

Background: The clinical significance of gastrointestinal (GI) symptoms in patients with severe fever and thrombocytopenia syndrome (SFTS) is poorly characterized. This study aimed to determine the prevalence and effect of GI symptoms on the prognosis of patients with SFTS. Methods: This was a retrospective multi-center cohort study that included hospitalized patients with SFTS from three institutions between October 2010 and August 2022. The risk factors for mortality and intensive care unit (ICU) admission were identified by Cox and logistic regression analyses, respectively. Kaplan-Meier curves were used to analyze the cumulative mortality risk. Results: Among 304 patients, the median age was 62.0 years and 51.0 % of the patients were male. A total of 202 patients (66.4 %) had at least one GI symptom on admission. Diarrhea (69.8 %) and nausea (57.4 %) were the most common symptoms. Patients with GI symptoms had lower male proportion (46.0 % vs. 60.8 %, P = 0.015), higher aspartate aminotransferase (177.5 U/L vs. 118.0 U/L, P = 0.010) and lactic dehydrogenase (771.0 U/L vs. 666.5 U/L, P = 0.017) levels than that of patients without GI symptoms. However, there was no significant difference in mortality rates (23.8 % vs. 21.6 %, P = 0.668) and ICU admission (14.4 % vs. 12.7 %, P = 0.701) between SFTS patients with and without GI symptoms. Multivariate analysis suggested that GI symptoms at admission were not associated with mortality and ICU admission. Conclusions: GI symptoms are common in patients with SFTS. However, the presence of GI symptoms was not an independent risk factor for poor prognosis.

Abstract Traditional tertiary oil recovery methods are fraught with challenges such as significant reagent adsorption, voluminous injection requirements, limited sweep efficiency, and inadequate intelligent targeting. These issues lead to suboptimal displacement of residual oil, resulting in the inability to mobilize substantial crude oil resources and thus yielding low recovery rates. Microcapsules—spherical particles with micron or nanometer scale diameters—have been extensively utilized across various sectors, including food storage, targeted drug encapsulation, and fragrance containment, owing to their distinct advantages in controlled release, isolation, and targeted delivery. These applications have successfully achieved industrialization and commercialization. In recent years, numerous researchers have explored the application of microcapsule preparation processes to diverse facets of oil extraction, with the aim of further enhancing oil recovery (EOR). This article elucidates the mechanism of action of microcapsules, their preparation methods (encompassing in situ polymerization, interfacial polymerization, spray drying, solvent evaporation, phase separation, and supercritical CO2‐assisted techniques), characterization and evaluation methodologies, among other aspects. It encapsulates the current status and principal challenges associated with the application of microcapsule preparation processes in oilfield development and probes the potential and pivotal research directions for their oilfield applications.

Parapristipoma trilineatum is an edible and economically important marine fish with high farming potential; however, this fish has not been widely investigated. To understand the germplasm resources of this marine fish, we investigated the range of P. trilineatum from Maizuru, Japan, to Hainan, China. Using the mitochondrial control region as a molecular marker, we analyzed the population structure, genetic diversity, and population history dynamics of P. trilineatum. The control region exhibited high haplotype diversity and nucleotide diversity of 0.996 and 0.016, respectively. The genetic differentiation coefficients indicated low differentiation between Japanese and other populations. Additionally, based on the results of SAMOVA, AMOVA, and genetic differentiation coefficients, P. trilineatum can be divided into two management units in fishery resources management: China and Japan. Populations with high genetic diversity are useful as genetic breeding materials. This study provides a basis for the selection and breeding of P. trilineatum.

Abstract Background Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. Results In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine’s capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. Conclusions The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout. Graphical Abstract

Abstract The basic requirements for the grid connection of the generator motor of the gravity energy storage system are: the phase sequence, frequency, amplitude, and phase of the voltage at the generator end and the grid end must be consistent. However, in actual working conditions, there will always be errors in the voltage indicators of the generator and grid terminals, resulting in transient impulse currents. In addition, due to the difference between gravity energy storage systems and conventional power generation units, frequent switching between charging and discharging operating conditions is required according to the needs of the power grid. Each switching requires the completion of the generator motor startup and grid connection. If there is always a significant error in the voltage indicators between the generator and grid terminals during frequent grid connection, stable transient surge currents will be generated. Without human intervention, long-term operation will bring hidden dangers to the safety of the grid connected system, leading to a series of consequences such as equipment aging and even damage. In response to the above issues, this article establishes a gravity energy storage power generation/motor grid connection model. Through simulation analysis, the variation law of the weight of the impact of different terminal voltage indicators on the grid connected transient impulse current is summarized. A grid connection method for gravity energy storage systems based on sensitivity analysis of voltage grid connection indicators is proposed. Through simulation verification, this method can significantly reduce the grid connected transient impulse current while improving the success rate of grid connection, The correctness and practicality of the proposed method have been fully verified.

Abstract Objective Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence‐associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi‐omics approach and to establish diagnostic assays for AD. Methods This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals. Plasma and serum samples were examined using high‐resolution mass spectrometry to identify proteomic and metabolomic profiles. Receiver operating characteristic (ROC) analysis was employed to screen biomarkers with diagnostic potential. K‐nearest neighbors (KNN) algorithm was utilized to construct a multi‐dimensional model for distinguishing AD from CN. Results Proteomics analysis revealed upregulation of five plasma proteins in AD, including RNA helicase aquarius (AQR), zinc finger protein 587B (ZNF587B), C‐reactive protein (CRP), fibronectin (FN1), and serum amyloid A‐1 protein (SAA1), indicating their potential for AD classification. Interestingly, KNN‐based three‐dimensional model, comprising AQR, ZNF587B, and CRP, demonstrated its high accuracy in AD recognition, with evaluation possibilities of 0.941, 1.000, and 1.000 for the training, testing, and validation datasets, respectively. Besides, metabolomics analysis suggested elevated levels of serum phenylacetylglutamine (PAGIn) in AD. Interpretation The multi‐omics outcomes highlighted the significance of the SASPs, specifically AQR, ZNF587B, CRP, and PAGIn, in terms of their potential for diagnosing AD and suggested neuronal aging‐associated pathophysiology.

Abstract The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Debris flow disasters in mountainous areas threaten the lives, property, and life of residents. Effective disaster reduction strategies are needed to reduce this potential risk. Through a comprehensive literature review and on-site inspections, this study identifies 16 factors impacting the risk of personnel loss. Subsequently, a risk assessment and response analysis model is developed utilizing Bayesian network (BN). The model includes debris flow risk assessment and personnel disaster resistance evaluation. By utilizing the expected maximum (EM) algorithm to analyze historical disaster data of Ya’an City over the past few years, model parameters for DFR assessment are derived. Additionally, quantitative standards for non-engineering measures are established and the Analytic Hierarchy Process is employed to obtain model parameters for PDR evaluation. Finally, these two components of the model are integrated and applied to a watershed within Ya’an City. The results of this application indicate that strengthening the construction of early warning systems in that watershed can effectively reduce the risk of personnel loss. The model is expected to provide a more scientific and comprehensive reference for debris flow risk assessment and response.

The response of Hypoxia Inducible Gene Domain (HIGD) proteins to hypoxia plays a crucial role in plant development. However, the research on this gene family in soybean has been lacking. In this study, we aimed to identify and comprehensively analyze soybean HIGD genes using the Glycine max genome database. As a result, six GmHIGD genes were successfully identified, and their phylogeny, gene structures, and putative conserved motifs were analyzed in comparison to Arabidopsis and rice. Collinearity analysis indicated that the HIGD gene family in soybean has expanded to some extent when compared to Arabidopsis. Additionally, the cis-elements in the promoter regions of GmHIGD and the transcription factors potentially binding to these regions were identified. All GmHIGD genes showed specific responsiveness to submergence and hypoxic stresses. Expression profiling through quantitative real-time PCR revealed that these genes were significantly induced by PEG treatment in root tissue. Co-expressed genes of GmHIGD were primarily associated with oxidoreductase and dioxygenase activities, as well as peroxisome function. Notably, one of GmHIGD genes, GmHIGD3 was found to be predominantly localized in mitochondria, and its overexpression in Arabidopsis led to a significantly reduction in catalase activity compared to wild-type plants. These results bring new insights into the functional role of GmHIGD in terms of subcellular localization and the regulation of oxidoreductase activity.

Summary: Timely adjustments of antibiotic and corticosteroid treatments are vital for patients with diffuse parenchymal lung diseases (DPLDs). In this study, 41 DPLD patients with negative metagenomic next-generation sequencing (mNGS) results who were responsive to corticosteroids were enrolled. Among these patients, about 26.8% suffered from drug-induced DPLD, while 9.8% presented autoimmune-related DPLD. Following the report of the negative mNGS results, in 34 patients with complete antibiotics administration profiles, 79.4% (27/34) patients discontinued antibiotics after receiving negative mNGS results. Moreover, 70.7% (29/41) patients began or increased the administration of corticosteroid upon receipt of negative mNGS results. In the microbiota analysis, Staphylococcus and Stenotrophomonas showed higher detection rates in patients with oxygenation index (OI) below 300, while Escherichia and Stenotrophomonas had higher abundance in patients with pleural effusion. In summary, our findings demonstrated the clinical significance of mNGS in assisting the antibiotic and corticosteroid treatment adjustments in corticosteroid-responsive DPLD. Lung microbiota may imply the severity of the disease.

Abstract Objective This study aims to identify the most effective diagnostic method for distinguishing pathogenic and non-pathogenic Gram-negative bacteria (GNB) in suspected pneumonia cases using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples. Methods The effectiveness of mNGS was assessed on BALF samples collected from 583 patients, and the results were compared with those from microbiological culture and final clinical diagnosis. Three interpretational approaches were evaluated for diagnostic accuracy. Results mNGS outperformed culture significantly. Among the interpretational approaches, Clinical Interpretation (CI) demonstrated the best diagnostic performance with a sensitivity of 87.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98.3%. CI’s specificity was significantly higher than Simple Interpretation (SI) at 37.9%. Additionally, CI excluded some microorganisms identified as putative pathogens by SI, including Haemophilus parainfluenzae, Haemophilus parahaemolyticus, and Klebsiella aerogenes. Conclusion Proper interpretation of mNGS data is crucial for accurately diagnosing respiratory infections caused by GNB. CI is recommended for this purpose.

In Synthetic aperture radar (SAR) recognition tasks, due to its special imaging principle, SAR images acquired from different viewpoints contain target features that may carry a large amount of information. However, if recognition is forced by fusion of multiview features when raw data is scarce, feature redundancy will be formed, which in turn will lead to a decrease in recognition accuracy. To remedy the above problem, a multiview inter-class dissimilarity feature fusion (MIDFF) network is proposed in this study. The proposed network has multiple parallel inputs and can extract multiview features and heterogeneous features. Firstly, a method for rapidly generating sufficient training data for MIDFF is proposed, which generates training data by repeatedly combining images from different views and classes to ensure that a large number of training inputs are available even when raw SAR images are scarce. Secondly, a method of calculating and enhancing of inter-class dissimilarity (ICD) features is proposed to increase the inter-class distance and improve the inter-class separability. Then, the ICD and multiview features are fused to increase the features learned by the network and reduce feature redundancy. Finally, a multiview heterogeneous weighted loss function is proposed, which combines the calculation of inter-class similarity and heterogeneous loss. Through the gradual convergence of the loss function, the inter-class similarity decreases as the loss decreases, which further improves the target recognition performance. Experimental results on MSTAR and Civilian Vehicle SAR datasets show that our proposed method performs better than the state-of-the-art methods within sample scarcity conditions.

Abstract Emerging evidence indicates that protein activities regulated by receptor protein tyrosine phosphatases (RPTPs) are crucial for a variety of cellular processes, such as proliferation, apoptosis, and immunological response. Protein tyrosine phosphatase receptor type O (PTPRO), an RPTP, has been revealed as a putative suppressor in the development of particular tumors. However, the function and the underlying mechanisms of PTPRO in regulating of lung adenocarcinoma (LUAD) are not well understood. In this view, the present work investigated the role of PTPRO in LUAD. Analysis of 90 pairs of clinical LUAD specimens revealed significantly lower PTPRO levels in LUAD compared with adjacent non-tumor tissue, as well as a negative correlation of PTPRO expression with tumor size and TNM stage. Survival analyses demonstrated that PTPRO level can help stratify the prognosis of LUAD patients. Furthermore, PTPRO overexpression was found to suppress the progression of LUAD both in vitro and in vivo by inducing cell death via mitochondria-dependent apoptosis, downregulating protein expression of molecules (Bcl-2, Bax, caspase 3, cleaved-caspase 3/9, cleaved-PARP and Bid) essential in cell survival. Additionally, PTPRO decreased LUAD migration and invasion by regulating proteins involved in the epithelial-to-mesenchymal transition (E-cadherin, N-cadherin, and Snail). Moreover, PTPRO was shown to restrain JAK2/STAT3 signaling pathways. Expression of PTPRO was negatively correlated with p-JAK2, p-STAT3, Bcl-2, and Snail levels in LUAD tumor samples. Furthermore, the anti-tumor effect of PTPRO in LUAD was significant but compromised in STAT3-deficient cells. These data support the remarkable suppressive role of PTPRO in LUAD, which may represent a viable therapeutic target for LUAD patients.

Abstract Background For brain metastases (BMs) from EGFR/ALK-positive non-small cell lung cancer (NSCLC), the best time to administer tyrosine kinase inhibitors (TKIs) and brain radiotherapy (RT) has not been identified. This analysis was an attempt to solve this problem in part. Methods A total of 163 patients with EGFR/ALK-positive NSCLC and brain metastasis (BM) who were diagnosed between January 2017 and July 2022 were included in this study. Ninety-one patients underwent upfront RT, and 72 patients received deferred RT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study. Results The average follow-up period was 20.5 months (range 2.0 to 91.9 months). The median overall survival (OS) was 26.5 months, and the median intracranial progression-free survival (iPFS) was 23.6 months. Upfront RT considerably increased the iPFS (26.9 vs. 20.2 months, hazard ratio [HR] = 5.408, P = 0.020) and OS (31.2 vs. 22.3 months, HR = 4.667, P = 0.031) compared to deferred RT. According to multivariate analysis, upfront RT was an independent risk factor for predicting iPFS (HR = 1.670, P = 0.021). Upfront RT (HR = 1.531, P = 0.044), TKI therapy (HR = 0.423, P

Abstract Background Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood. Methods Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3. Results The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells. Conclusions Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti-M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5′ and C-6′, exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5′ and C-6′ on this compound’s activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5′ and C-6′. The R/S configuration of the diastereoisomer at C-13′ was further determined through an NOE correlation analysis of CH3 or CH2 at the derivative C-13′ position and the H-5′ and H-6′ by means of a 1D NOE experiment. Further comparative 1H NMR analysis of diastereoisomers showed the difference in the chemical shift (δ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15–24 and 28–35 demonstrated promising activity against M. marinum, with MIC90 values ranging from 70 to 90 μM, closely approaching the MIC90 of isoniazid. The preliminary structure–activity relationships showed that the ketal groups with aromatic rings at C-5′ and C-6′ could enhance the inhibition of M. marinum. Further study demonstrated that compounds 23, 24, 29, and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Although it is well established that thermal environments significantly influence travel behavior, the synergistic effects of points of interest (POI) and thermal environments on behavior remain unclear. This study developed a vision-based outdoor evaluation model aimed at uncovering the driving factors behind human behavior in outdoor spaces. First, Yolo v5 and questionnaires were employed to obtain crowd activity intensity and preference levels. Subsequently, target detection and clustering algorithms were used to derive variables such as POI attractiveness and POI distance, while a validated environmental simulator was utilized to simulate outdoor thermal comfort distributions across different times. Finally, multiple classification models were compared to establish the mapping relationships between POI, thermal environment variables, and crowd preferences, with SHAP analysis used to examine the contribution of each variable. The results indicate that XGBoost achieved the best predictive performance (accuracy = 0.95), with shadow proportion (|SHAP| = 0.24) and POI distance (|SHAP| = 0.12) identified as the most significant factors influencing crowd preferences. By extrapolation, this classification model can provide valuable insights for optimizing community environments and enhancing vitality in areas with similar climatic and cultural contexts.

Abstract Plant movements for survival are nontrivial. Antheridia in the moss Physcomitrium patens (P. patens) use motion to eject sperm in the presence of water. However, the biological and mechanical mechanisms that actuate the process are unknown. Here, the burst of the antheridium of P. patens, triggered by water, results from elastic instability and is determined by an asymmetric change in cell geometry. The tension generated in jacket cell walls of antheridium arises from turgor pressure, and is further promoted when the inner walls of apex burst in hydration, causing water and cellular contents of apex quickly influx into sperm chamber. The outer walls of the jacket cells are strengthened by NAC transcription factor VNS4 and serve as key morphomechanical innovations to store hydrostatic energy in a confined space in P. patens. However, the antheridium in liverwort Marchantia polymorpha (M. polymorpha) adopts a different strategy for sperm release; like jacket cell outer walls of P. patens, the cells surrounding the antheridium of M. polymorpha appear to play a similar role in the storage of energy. Collectively, the work shows that plants have evolved different ingenious devices for sperm discharge and that morphological innovations can differ.

ObjectivesSevere fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS.MethodsA total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks.Results60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 μmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome.ConclusionsLiver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

BackgroundPreeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors.MethodsWe retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24–45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher’s exact test and Mann–Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors.ResultsBy using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively.ConclusionIncorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

ABSTRACTBovine enterovirus (BEV) consisting of enterovirus species E (EV-E) and F (EV-F) is the causative agent associated with respiratory and gastrointestinal diseases in cattle. Here, we reported the characterization, genetic diversity, and recombination of novel BEV strains isolated from the major cattle-raising regions in China during 2012–2018. Twenty-seven BEV strains were successfully isolated and characterized. Molecular characterization demonstrated that the majority of these novel BEV strains (24/27) were EV-E, while only few strains (3/27) were EV-F. Sequence analysis revealed the diversity of the circulating BEV strains such as species and subtypes where different species or subtype coinfections were detected in the same regions and even in the same cattle herds. For the EV-E, two novel subtypes, designated as EV-E6 and EV-E7, were revealed in addition to the currently reported EV-E1–EV-E5. Comparative genomic analysis revealed the intraspecies and interspecies genetic exchanges among BEV isolates. The representative strain HeN-B62 was probably from AN12 (EV-F7) and PS-87-Belfast (EV-F3) strains. The interspecies recombination between EV-E and EV-F was also discovered, where the EV-F7-AN12 might be from EV-E5 and EV-F1, and EV-E5-MexKSU/5 may be recombined from EV-F7 and EV-E1. The aforementioned results revealed the genetic diversity and recombination of novel BEV strains and unveiled the different BEV species or subtype infections in the same cattle herd, which will broaden the understanding of enterovirus genetic diversity, recombination, pathogenesis, and prevention of disease outbreaks.IMPORTANCEBovine enterovirus (BEV) infection is an emerging disease in China that is characterized by digestive, respiratory, and reproductive disorders. In this study, we first reported two novel EV-E subtypes detected in cattle herds in China, unveiled the coinfection of two enterovirus species (EV-E/EV-F) and different subtypes (EV-E2/EV-E7, EV-E1/EV-E7, and EV-E3/EV-E6) in the same cattle herds, and revealed the enterovirus genetic exchange in intraspecies and interspecies recombination. These results provide an important update of enterovirus prevalence and epidemiological aspects and contribute to a better understanding of enterovirus genetic diversity, evolution, and pathogenesis.

Pancreatic cancer is a highly aggressive malignancy of the digestive system, with occult onset, rapid progression, and poor prognosis. The genetic heterogeneity of pancreatic cancer contributes to its highly malignant biological behavior. HMGA2 is overexpressed in tumors and is known to regulate tumor progression in various cancers through the HMGA2-IGF2BP2 axis, but its role and mechanism in pancreatic cancer remain unclear. In this study, we demonstrated that HMGA2 promotes pancreatic cancer progression. We further revealed that HMGA2 upregulates IGF2BP2, which stabilizes APLP2 mRNA via m6A modification, thereby promoting pancreatic cancer progression. These results indicate that HMGA2/IGF2BP2/APLP2 signaling axis regulates the progression of pancreatic cancer.

Abstract Background Identifying age-related trend of estimated glomerular filtration rate (eGFR) is necessary to assess whether kidney function is healthily aging. This study aimed to investigate the application of CKD-EPI, FAS, and Xiangya equations for the aging estimation of eGFR in the healthy Chinese individuals. Methods A total of 36,911 healthy individuals were enrolled in this study. We grouped every ten years to observe the trend of eGFR with aging and investigated decline rate of it by general linear regression analysis in each age-groups. Agreement between equations was determined by intraclass correlation coefficient (ICC) and Bland–Altman plot. We calculated reference interval in each age-group. We further analyzed above statistical indicators in males and females. Results The eGFR by CKD-EPI, and Xiangya equation started to decline from the age of 18. Whereas eGFR by FAS equation remained stable under 40 years, then decreased more rapidly. Compared with males, the females had a higher level but a faster decline rate of eGFR with aging. Agreement analysis revealed good agreement between CKD-EPI and FAS equations (ICC 0.818–0.920). Agreement between Xiangya and CKD-EPI or FAS equations was poor to moderate in most of the population under 70 years old (ICC 0.282–0.786), but good in individuals above 70 years (ICC 0.769–0.881). Conclusions The trend of eGFR with aging was different by CKD-EPI, FAS, and Xiangya equations in the healthy Chinese. It may be necessary to take these equations- or age-related differences into consideration when assessing kidney function in primary health care and clinical practice.

Abstract Emerging evidence indicates that DNA methylation plays an important role in the initiation and progression of nasopharyngeal carcinoma (NPC). DNAJA4 is hypermethylated in NPC, while its role in regulating NPC progression remains unclear. Here, we revealed that the promoter of DNAJA4 was hypermethylated and its expression was downregulated in NPC tissues and cells. Overexpression of DNAJA4 significantly suppressed NPC cell migration, invasion, and EMT in vitro, and markedly inhibited the inguinal lymph node metastasis and lung metastatic colonization in vivo, while it did not affect NPC cell viability and proliferation capability. Mechanistically, DNAJA4 facilitated MYH9 protein degradation via the ubiquitin-proteasome pathway by recruiting PSMD2. Furthermore, the suppressive effects of DNAJA4 on NPC cell migration, invasion, and EMT were reversed by overexpression of MYH9 in NPC cells. Clinically, a low level of DNAJA4 indicated poor prognosis and an increased probability of distant metastasis in NPC patients. Collectively, DNAJA4 serves as a crucial driver for NPC invasion and metastasis, and the DNAJA4-PSMD2-MYH9 axis might contain potential targets for NPC treatments.

To comprehensively analyze the composition and contribution of volatile components in Rosa sterilis, the headspace solid phase microextraction (HS-SPME) and liquid liquid extraction with solvent assisted flavor evaporation (LLE-SAFE) was used, along with gas chromatography-mass spectrometry (GC-MS) to analyze the volatile components. The odor active value (OAV) was used to evaluate the contribution of volatile components to the overall aroma of R. sterilis juice. The results showed that a total of 115 volatile components were identified using both methods, with 59 identified using HS-SPME and 75 identified using LLE-SAFE. These components included 25 esters, 27 alcohols, 11 aldehydes, 14 ketones, 18 acids, 14 terpenes, and 6 other compounds. Analysis of the odor active value (OAV) showed that 30 volatile components, including isoamyl alcohol, 2-hexenal, ethyl hexanoate, ethyl acetate, butyl acetate, hexanal, and hexanoic acid, contributed strongly to the aroma of R. sterilis. This study provides theoretical support for revealing the aroma profile and chemical essence of R. sterilis.

Abstract Aim The study aimed to investigate the short‐term outcomes of hospitalized patients with chronic liver disease (CLDs) and assess the prognostic impact of predisposition and precipitants, which currently remains unclear. Methods The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies (NCT02457637 and NCT03641872) conducted in highly endemic hepatitis B virus (HBV) areas. Competing risk analysis was used to evaluate the effect of predispositions, including the etiology and severity of CLDs and precipitants; on sequential 28, 90, and 365‐day liver transplantation (LT)‐free mortality. Results Among all enrolled patients, 76.8% of adverse outcomes (including death and LT) within one year occurred within 90 days. Compared with alcoholic etiology, the association of HBV etiology with poorer outcomes was remarkably on the 28th day (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.07–3.06; p = 0.026); however, and diminished or became insignificant at 90 days and 365 days. Cirrhosis increased the adjusted risk for 365‐day (HR, 1.50; CI, 1.13–1.99; p = 0.004) LT‐free mortality when compared with noncirrhosis. In patients with cirrhosis, prior decompensation (PD) independently increased the adjusted risk of 365‐day LT‐free mortality by 1.25‐fold (p = 0.021); however, it did not increase the risk for 90‐day mortality. Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90‐day LT‐free mortality. Conclusions The 90‐day outcome should be considered a significant endpoint for evaluating the short‐term prognosis of hospitalized patients with CLD. Predisposing factors, other than etiology, mainly affected the delayed (365‐day) outcome. Timely effective therapy for CLD etiology, especially antiviral treatments for HBV, and post‐discharge long‐term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.

Abstract Objectives The aim of this study was to compare the metastatic patterns of synchronous bone metastasis (SBM) and metachronous bone metastasis (MBM) in nasopharyngeal carcinoma (NPC). Methods This study included bone metastases in NPC patients from 2005 to 2016 in a Chinese hospital. Cohort 1 was collected from 2005 to 2010 for discovery, and Cohort 2 from 2011 to 2016 for validation. The chi‐squared test, Wilcoxon rank sum test, and Kaplan–Meier technique were used to compare site, time, and survival between cohorts 1 and 2. Prognostic factors were analyzed using univariate or multivariate Cox regression. Results Cohort 1 had 112 individuals with SBM and 394 with MBM, and cohort 2 had 328 with SBM and 307 with MBM. The thoracic vertebra was the most frequently affected site of metastasis. Patients with SBM more often had metastasis to the cervical vertebrae compared with patients with MBM (34.5% vs. 22.3%, p

Abstract Background The relationship between metabolically healthy obese individuals (MHO) and cardiovascular disease (CVD) risk is disputed. This study investigated the association of metabolically unhealthy non-obese(MUNO) individuals and MHO with arterial stiffness and 10-year CVD risk. Methods A total of 13,435 participants were enrolled and further divided into the metabolically healthy non-obese (MHNO) phenotype (n = 4927), MUNO phenotype (n = 1971), MHO phenotype (n = 2537) and metabolically unhealthy obese (MUO) phenotype (n = 4000) according to body mass index (BMI) and metabolic status. We used brachial ankle pulse wave velocity (baPWV) to measure arterial stiffness and the Framingham risk score (FRS) to evaluate the 10-year CVD risk. Results The MUO and MUNO phenotypes had higher mean baPWV values than the MHO and MHNO phenotypes, regardless of age (1446.19 ± 233.65 vs. 1423.29 ± 240.72 vs. 1283.57 ± 213.77 vs. 1234.08 ± 215.99 cm/s, P

CO2-enhanced oil recovery (CO2-EOR) is a crucial method for CO2 utilization and sequestration, representing an important zero-carbon or even negative-carbon emission reduction technology. However, the low viscosity of CO2 and reservoir heterogeneity often result in early gas breakthrough, significantly reducing CO2 utilization and sequestration efficiency. A water-alternating-gas (WAG) injection is a technique for mitigating gas breakthrough and viscous fingering in CO2-EOR. However, it encounters challenges related to insufficient mobility control in highly heterogeneous and fractured reservoirs, resulting in gas channeling and low sweep efficiency. Despite the extensive application and research of a WAG injection in oil and gas reservoirs, the most recent comprehensive review dates back to 2018, which focuses on the mechanisms of EOR using conventional WAG. Herein, we give an updated and comprehensive review to incorporate the latest advancements in CO2-WAG flooding techniques for enhanced sweep efficiency, which includes the theory, applications, fluid displacement mechanisms, and control strategies of a CO2-WAG injection. It addresses common challenges, operational issues, and remedial measures in WAG projects by covering studies from experiments, simulations, and pore-scale modeling. This review aims to provide guidance and serve as a reference for the application and research advancement of CO2-EOR techniques in heterogeneous and fractured reservoirs.

Estimating the impact of pesticide residue bioaccessibility in fruits on dietary exposure is a complex task in human health risk assessment. This research investigated the bioaccessibility of ten commonly used and detected pesticides in bananas and mangoes, as well as the factors influencing it, using an in vitro model. The highest bioaccessibility was observed at pH levels of 2.5 and 6.5 in the gastric and intestinal stages, respectively. Bioaccessibility decreased significantly with increasing solid/liquid ratios for most pesticides. The consumption of protein and four dietary components (carbohydrates, protein, lipids, and dietary fiber) could significantly reduce pesticide bioaccessibility by 9.89–48.32% (p < 0.05). Bioaccessibility in oral and gastric stages among four populations followed the order of adults/the elderly > children > infants, due to decreasing concentrations of α-amylase and pepsin. Pesticides in bananas generally exhibited a higher bioaccessibility (18.65–82.97%) compared to that in mangoes (11.68–87.57%). Bioaccessibility showed a negative correlation with the Log P values of the target pesticide, while no clear relationship was found between bioaccessibility and initial pesticide concentrations. Incorporating bioaccessible pesticide concentrations into risk assessments could lower dietary risk estimates by 11.85–79.57%. Assessing human exposure to pesticides based on bioaccessibility would greatly improve the accuracy of the risk assessment.

Here, we report the discovery of two viruses associated with a disease characterized by severe diarrhea on a large-scale goat farm in Jilin province. Electron Microscopy observations revealed two kinds of virus particles with the sizes of 150–210 nm and 20–30 nm, respectively. Detection of 276 fecal specimens from the diseased herds showed the extensive infection of peste des petits ruminants virus (63.77%, 176/276) and caprine enterovirus (76.81%, 212/276), with a co-infection rate of 57.97% (160/276). These results were partially validated with RT-PCR, where all five PPRV-positive and CEV-positive specimens yielded the expected size of fragments, respectively, while no fragments were amplified from PPRV-negative and CEV-negative specimens. Moreover, corresponding PPRV and CEV fragments were amplified in PPRV and CEV double-positive specimens. Histopathological examinations revealed severe microscopic lesions such as degeneration, necrosis, and detachment of epithelial cells in the bronchioles and intestine. An immunohistochemistry assay detected PPRV antigens in bronchioles, cartilage tissue, intestine, and lymph nodes. Simultaneously, caprine enterovirus antigens were detected in lung, kidney, and intestinal tissues from the goats infected by the peste des petits ruminants virus. These results demonstrated the co-infection of peste des petits ruminants virus with caprine enterovirus in goats, revealing the tissue tropism for these two viruses, thus laying a basis for the future diagnosis, prevention, and epidemiological survey for these two virus infections.

Compared with traditional Electromagnetic (EM) wave radars, vortex EM wave radars can simultaneously observe the micro-motion components projected onto the radar’s radial and perpendicular planes, providing more information for target recognition. The current research on the micro-Doppler effect of vortex EM wave radar is still in its infancy, and the extraction of three-dimensional micro-motion parameters of rotating targets has been preliminarily achieved. However, the impact of target translation was not considered. Therefore, the micro-Doppler effect of translational rotating targets in vortex EM wave radar is studied in this paper. The angular Doppler properties of translational rotating targets are derived, and a three-dimensional micro-motion parameter extraction method based on the 1/4 micro-motion period Doppler frequency shift curve is proposed. Estimation of parameters such as target rotation frequency, rotation radius, rotation vector and translational velocity vector is achieved. The correctness of angular Doppler properties and the effectiveness of parameter extraction method are verified by simulations.

Abstract Background Circ_0000376 could promote non‐small cell lung cancer (NSCLC) progression; however, the role of circ_0000376 in paclitaxel (PTX) resistance of NSCLC is still unknown. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were applied for measuring circ_0000376, microRNA‐1298‐5p (miR‐1298‐5p), and karyopherin subunit alpha 4 (KPNA4) expression. The half inhibitory concentration (IC50) of PTX was assessed by cell counting kit‐8 assay. 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, and flow cytometry were performed to measure the proliferation, migration, invasion, and apoptosis of cells. The regulatory mechanisms of circ_0000376, miR‐1298‐5p, and KPNA4 were validated by dual‐luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. Xenograft assay was used for the functional analysis of circ_0000376 in vivo. Results Circ_0000376 and KPNA4 expressions were upregulated, while miR‐1298‐5p expression was downregulated in PTX‐resistant tissues and cells. Circ_0000376 depletion promoted PTX sensitivity and apoptosis, while suppressing the proliferation, migration, and invasion of PTX‐resistant NSCLC cells. Furthermore, circ_0000376 could modulate KPNA4 expression by sponging miR‐1298‐5p. Rescue experiments showed that miR‐1298‐5p inhibition reversed the circ_0000376 depletion‐mediated anticancer effects and PTX sensitivity. Moreover, miR‐1298‐5p inhibited PTX resistance and tumorigenesis of PTX‐resistant cells, which were abolished by KPNA4 overexpression. In addition, circ_0000376 knockdown suppressed tumor growth and enhanced PTX sensitivity in vivo. Conclusion Circ_0000376 facilitated PTX resistance and tumorigenesis of NSCLC by miR‐1298‐5p/KPNA4 axis, suggesting an underlying therapeutic strategy for NSCLC.

Abstract Background Recently, periumbilical fat (PF) mass, an autologous material with a high survival rate, has been transplanted to treat sunken or dissatisfactory double eyelids. However, the intricate complications of PF grafts and associated reconstructive strategies are infrequently discussed. Methods During 3 years, 20 patients (33 eyes) with eyelid malformations caused by PF grafts into the orbital septum or on the surface of the levator aponeurosis underwent corrective blepharoplasty. We recorded patients’ subjective feelings and identified deformities from crease abnormalities, bloated appearance, and problems with the eyelid’s height. Then, we categorize them into three types based on their complexity: type I, swollen appearance; type II, obvious adhesion; type III, severe comprehensive damage. The relevant management included removing fat implants, releasing the adhesion, and rebuilding the physical structure according to the anatomic damage mechanism. The improvement effect was assessed with a satisfaction survey from patients and doctors at 6 months of follow-up. Results The swollen appearance was observed in 26 eyes (78.8%), an unsmooth double-eyelid line was in 23 eyes (69.7%), and the incidence of adhesion was in 22 eyes (66.7%). Following a comprehensive evaluation, 15 eyes (45.5%) and 13 (39.4%) were classified as type I and type II respectively. After the 6-month follow-up, 22 eyes (66.7%) showed exceptional aesthetic results, whereas only 2 eyes as type III had a poor outcome. Conclusions The deformities emerging from periumbilical fat into the upper eyelid are associated with the shape of the fat and the adhesion in tissues. Graft removal, adhesion release, and restoration of the natural anatomic structure can have positive outcomes.

Plant growth regulators can effectively improve the yield and quality of fruits and vegetables, and their application in fruit and vegetable production is increasing. The risk assessment of plant growth regulator residues has also become a research hotspot. The paper reviews the main categories, functions and application status of plant growth regulators in fruits and vegetables. The harm and residue status of several main growth regulators such as paclobutrazol, forchlorfenuron, gibberellic acid, ethephon and 2,4-dichlorophenoxyacetic acid (2,4-D) in fruits and vegetables are summarized and analyzed. It is found that the average residue of ethephon in fruits and vegetables is the highest, and the residue of plant growth regulator in fruits and vegetables such as grapes, bean sprouts and strawberries is the most serious, and its potential safety hazards should be paid attention to. However, the current national plant growth regulator standards do not cover some fruits and vegetables. It is urgent to improve the relevant standards and risk assessment of plant growth regulator residues.

Abstract The transcriptional repressor Snail induces EMT during embryonic development and tumor metastasis. Growing evidence indicates that Snail functions as a trans-activator to induce gene expression; however, the underlying mechanism remains elusive. Here, we report that Snail cooperates with GATA zinc finger protein p66β to transactivate genes in breast cancer cells. Biologically, depletion of p66β reduces cell migration and lung metastasis in BALB/c mice. Mechanistically, Snail interacts with p66β and cooperatively induces gene transcription. Notably, a group of genes induced by Snail harbor conserved G-rich cis-elements (5′-GGGAGG-3′, designated as G-box) in their proximal promoter regions. Snail directly binds to G-box via its zinc fingers and transactivates the G-box-containing promoters. p66β enhances Snail binding affinity to G-box, whereas depletion of p66β results in a decreased binding affinity of Snail to the endogenous promoters and concomitantly reduces the transcription of Snail-induced genes. Taken together, these data demonstrated that p66β is critical for Snail-mediated cell migration by acting as a co-activator of Snail to induce genes containing G-box elements in the promoters.

Abstract Our previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn-induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn-induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn-specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn, including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn-caused NAFLD.

Peptides are widely used as natural bio-small molecules because of their various pharmacological activities such as enhancing immunity, promoting wound healing, and improving inflammation. Alcoholic heart injury has become one of the major health problems worldwide, and alcohol consumption is now the main cause of alcoholic cardiomyopathy. In this study, deer heart peptides were extracted from deer hearts by enzymatic digestion and the antioxidant activity of deer heart peptides extracted at different times was evaluated by three in vitro antioxidant methods, and the active peptide with the best enzymatic effect has been selected for in vivo animal experiments. The anti-inflammatory and antioxidant properties of deer heart enzymatic extracts were evaluated in in vivo experiments in mice. In this study, mice were orally gavaged with white wine (12 mL/kg body weight) to induce a mouse model of cardiac injury, while mice were orally administered a single dose of 100 mg/kg/bw and 200 mg/kg/bw of deer heart enzyme digest and were examined for body weight, dietary intake, water intake, and coat gloss, as well as for general behaviors, adverse effects, and mortality. Histology, serum, anti-inflammatory factors, and oxidative stress parameters were subsequently assessed. In all modeled mice, no four-way or any significant behavioral changes were observed in all groups, but in the modeled group, mice showed weight loss, decreased diet and water intake, and decreased cardiac index. For in vivo tests, the extract inhibited the anti-inflammatory activity with a significant decrease in inflammatory factors of TNF-α, IL-6, and IL-1β in cardiac tissues, a significant increase in serum levels of both CAT and SOD, an increase in MDA content, and a remarkable increase in the level of the marker CK in the cardiac myocardial enzyme profile. Significant improvement in myocardial disorders by deer heart peptide could be observed from heart tissue sections. The present study emphasizes the anti-inflammatory and antioxidant activity of deer heart peptide, an enzymatic digest of deer heart, which provides empirical as well as supportive role for the anti-inflammatory properties of traditional medicine.

The broad-banded velvetchin Hapalogenys analis is an economically and scientifically important global temperate and tropical nearshore marine fish. To understand the genetic evolution mechanism of H. analis, simplified genome sequencing analysis was conducted on 82 samples of H. analis from three populations (Akashi, Zhoushan, and Shantou) in the northwestern Pacific Ocean using double-digest restriction site-associated DNA sequencing. Genetic characteristics were identified using single-nucleotide polymorphism loci, and a small fragment library (250–450 bp long) was constructed for double-end sequencing. Single-nucleotide polymorphisms (SNPs) were detected using Stacks software and analyzed. The phylogenetic tree was constructed to analyze the population structure characteristics and the genetic evolutionary relationships between individuals in different regions at the genetic level. The sequencing library constructed for 82 samples of H. analis using double-digest restriction site-associated DNA sequencing possessed an average of 7,931,195 sequencing sequences and an average of 1,141,560,806 bases in the 82 samples. A total of 3,204,106 SNP loci were obtained from the three populations of H. analis, indicating rich genetic diversity. The transition to transversion ratio of SNPs was >1.5, indicating transformational reversal bias in H. analis. The observed heterozygosity of the various populations was 0.186–0.199, with an expected heterozygosity of 0.253–0.268. High diversity in all three populations was detected using nucleotide diversity analysis. AS and ZS had the highest degree of differentiation. The H. analis samples shared two gene libraries; some populations were closely related, whereas others had a distant genetic relationship. The results of genetic statistics, genetic differentiation, population structure, principal component, phylogenetic, and genetic relationship analyses supported independent clustering of the AS population, which can be used as a new genetic resource for conserving H. analis. These results provide a reference basis for comparative genomics studies of H. analis and rational utilization of Hapalogenys resources.

The brushtooth lizardfish, Saurida undosquamis (Richardson, 1848), is a valuable warm-water bottom fish with medicinal and economic value. This study utilized mitochondrial DNA cytochrome b (Cytb) and control region (CR) sequences to study the genetic diversity, population structure, and historical dynamics of four S. undosquamis populations in the South China Sea. Results showed that the alignment length of Cytb was 892 bp and that of the CR was 969 bp. In total, 59 polymorphic loci were detected in Cytb, defining 58 haplotypes. The overall haplotype and nucleotide diversity of the four populations were 0.9497 and 0.0041, respectively, and 104 polymorphic loci were detected in the CR, defining 97 haplotypes. The overall haplotype and nucleotide diversity of the four populations were 0.9980 and 0.0109, respectively. The haplotype phylogenetic tree, haplotype network diagram, and genetic differentiation index revealed no significant genetic differences among the four S. undosquamis populations. The results of the neutral test and mismatch analysis indicated that S. undosquamis expanded between 30.1 and 55.4 thousand years ago. The genetic diversity indicators obtained in this study will serve as basic data for future mitochondrial DNA polymorphism monitoring and research on S. undosquamis fishery resources.