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The identification of benign and malignant lung nodules is crucial for timely treatment to reduce the risk of the progression and metastasis of diseases. However, the varied sizes, diverse morphologies, non-fixed positions, and dynamic growth of lung nodules in computed tomography (CT) images make their accurate identification challenging. To address these issues, we propose a multi-scale transformer-based diagnosis (MSTD) method for benign and malignant lung nodules. To handle significant variations in the shapes and sizes of the lung nodules, we first design a multi-scale module based on parallel branches to extract multi-scale features. To make full use of these features, we then introduce a multi-scale transformer fusion (MSTF) module to integrate the information obtained at different scales. Unlike conventional vision transformers, our MSTF can simultaneously extract attention-based features from the spatial dimensions at different scales to enhance the accuracy of classification of lung nodules. We conducted extensive ablation experiments on multi-scale structures and transformer-based methods of fusion to explore the impact of features obtained at different scales on the accuracy of classification of lung nodules. The results of verification on the LUNA16 dataset showed that the average F1Score, Specificity, and Sensitivity of the proposed MSTD exceeded 90% (94.5%, 96.5%, and 91.1%, respectively), where this shows that it can accurately identify both benign and malignant lung nodules. Its average performance was superior to the state-of-the-art method by about 1%, 3.4%, and 3.6% in terms of the area under the curve (AUC), Accuracy, and F1Score, respectively.

Abstract Methane (CH4) photocatalytic upgrading to value-added chemicals, especially C2 products, is significant yet challenging due to sluggish energy/mass transfer and insufficient chemical driven-force in single photochemical process. Herein, we realize solar-driven CH4 oxidation to ethanol (C2H5OH) on crystalline carbon nitride (CCN) modified with Cu9S5 and Cu single atoms (Cu9S5/Cu-CCN). The integration of photothermal effect and photocatalysis overcomes CH4-to-C2H5OH conversion bottlenecks, with Cu9S5 as a hotspot to convert solar-energy to heat. In-situ characterizations demonstrate that Cu single atoms play as electron acceptor for O2 reduction to ·OOH/ · OH, while Cu9S5 acts as hole acceptor and site for CH4 adsorption, C − H activation, and C − C coupling. Theoretical calculations demonstrate that Cu9S5/Cu-CCN reduces C − C coupling energy barrier by stabilizing ·CH3 and ·CH2O. Impressively, C2H5OH productivity reaches 549.7 μmol g–1 h–1, with selectivity of 94.8% and apparent quantum efficiency of 0.9% (420 nm). This work provides a sustainable avenue for CH4 conversion to value-added chemcials.

Abstract In situ electrochemistry on micron and submicron-sized individual particles and thin layers is a valuable, emerging tool for process understanding and optimization in a variety of scientific and technological fields such as material science, process technology, analytical chemistry, and environmental sciences. Electrochemical characterization and manipulation coupled with soft X-ray spectromicroscopy helps identify, quantify, and optimize processes in complex systems such as those with high heterogeneity in the spatial and/or temporal domain. Here we present a novel platform optimized for in situ electrochemistry with variable liquid electrolyte flow in soft X-ray scanning transmission X-ray microscopes (STXM). With four channels for fluid control and a modular design, it is suited for a wealth of experimental conditions. We demonstrate its capabilities by proving the reversible oxidation and reduction of individual microbial biofilm structures formed by microaerophilic Fe(II)-oxidizing bacteria, also known as twisted stalks. We show spectromicroscopically the heterogeneity of the redox activity on the submicron scale. Examples are also provided of electrochemical modification of liquid electrolyte species (Fe(II) and Fe(III) cyanides), and in situ studies of electrodeposited copper nanoparticles as CO2 reduction electrocatalysts under reaction conditions.

In advanced hepatocellular carcinoma (HCC) tissues, M2-like tumor-associated macrophages (TAMs) are in the majority and promotes HCC progression. Contrary to the pro-tumor effect of M2-like TAMs, M1-like TAMs account for a small proportion and have anti-tumor effects. Since TAMs can switch from one type to another, reprogramming TAMs may be an important treatment for HCC therapy. However, the mechanisms of phenotypic switch and reprogramming TAMs are still obscure. In this study, we analyzed differential genes in normal macrophages and TAMs, and found that loss of MANF in TAMs accompanied by high levels of downstream genes negatively regulated by MANF. MANF reprogrammed TAMs into M1 phenotype. Meanwhile, loss of MANF promoted HCC progression in HCC patients and mice HCC model, especially tumor neovascularization. Additionally, macrophages with MANF supplement suppressed HCC progression in mice, suggesting MANF supplement in macrophage was an effective treatment for HCC. Mechanistically, MANF enhanced the HSF1–HSP70-1 interaction, restricted HSF1 in the cytoplasm of macrophages, and decreased both mRNA and protein levels of HSP70-1, which in turn led to reprogramming TAMs, and suppressing neovascularization of HCC. Our study contributes to the exploration the mechanism of TAMs reprogramming, which may provide insights for future therapeutic exploitation of HCC neovascularization.

Abstract Although perovskite solar cells (PSCs) are promising next generation photovoltaics, the production of PSCs might be hampered by complex and inefficient procedures. This Review outlines important advances in materials and methods for the cost-effective manufacturing of PSCs, including precursor synthesis, selection criteria for precursors based on chemistry, additive engineering, and deposition techniques. The goal of these technologies is not only to improve the performance and stability of PSCs, but also to significantly reduce their manufacturing costs. These advances are critical to the commercialization of PSCs, in terms of making them viable and cost-effective.

Abstract Background Generalized anxiety (GA) is showing a high prevalence among adolescents nowadays; investigations on influencing factors and potential mechanisms are important to inform intervention development. The present two-wave study investigated the ways in which family functioning predicted GA six months later among adolescents, by considering the mediating role of self-identity and cognitive flexibility. Methods Adolescents were recruited from 27 randomly selected classes in two secondary schools in Chongqing and Fujian Province, China. Survey questionnaires assessing family functioning, self-identity, cognitive flexibility and GA were obtained from 1223 adolescents (M age = 13.14, SD = 1.35) at two time points of the 6-month interval. Results The association between family functioning (T1) and GA (T2) was significant (r= -0.152, p

Underground engineering often passes through water-rich fractured rock masses, which are prone to fracture and instability under the long-term coupling of in-situ stress field and pore water (P-W) pressure, ultimately threatening the stability of underground structures. In order to explore the mechanical properties of rocks under H-M coupling, the corresponding damage constitutive (D-C) model has become the focus of attention. Considering the inadequacy of the current research on rock strength parameters, energy evolution characteristics and D-C model under H-M coupling, the mechanical properties of typical sandstone samples are discussed based on laboratory tests. The results show that the variation of characteristic stresses of sandstone under H-M coupling conforms to the normalized attenuation equation and Mohr-Coulomb (M−C) criterion. The P-W pressure mechanism of sandstone exhibits a dynamic change from softening effect to H-M fracturing effect. The closure stress is mainly provided by cohesive strength, while the initiation stress, damage stress, and peak stress are jointly dominated by cohesive strength and friction strength. In addition, residual stress is attributed to the friction strength formed by the bite of the fracture surface. Subsequently, the energy evolution characteristics of sandstone under H-M coupling were studied, and it was found that P-W pressure weakened the energy storage capacity and energy dissipation capacity of sandstone, and H-M fracturing was an important factor in reducing its energy storage efficiency. Finally, combined with energy dissipation theory and statistical damage theory, two types of D-C models considering P-W pressure are proposed accordingly, and the model parameters can be determined by four methods. The application results indicate that the proposed and modified D-C models have high reliability, and can characterize the mechanical behavior of sandstone under H-M coupling, overcome the inconvenience of existing D-C models due to excessive mechanical parameters, and can be applied to the full-range stress–strain process. The results are conducive to revealing the deformation and damage mechanisms of rocks under H-M coupling, and can provide theoretical guidance for related engineering problems.

Employee turnover has a negative impact on business profitability. To tackle this issue, we can utilize computational advancements to forecast attrition and minimize expenses. We employed an HR Analytics dataset to investigate the feasibility of using these predictive models in decision support systems. We developed an ensemble of gradient-based decision trees that accurately predicted employee turnover and performed better than other sophisticated techniques. This approach demonstrates exceptional performance in handling structured and imbalanced data, effectively capturing intricate patterns. Gradient-based decision trees provide scalable solutions that effectively balance predictive accuracy and computational efficiency, making them well-suited for strategic business analysis. The importance of our findings lies in their ability to offer dependable insights for making well-informed decisions in business settings.

Objectives Although neoadjuvant immunochemotherapy has been widely applied in non-small cell lung cancer (NSCLC), predicting treatment response remains a challenge. We used pretreatment multimodal CT to explore deep learning-based immunochemotherapy response image biomarkers.Methods This study retrospectively obtained non-contrast enhanced and contrast enhancedbubu CT scans of patients with NSCLC who underwent surgery after receiving neoadjuvant immunochemotherapy at multiple centers between August 2019 and February 2023. Deep learning features were extracted from both non-contrast enhanced and contrast enhanced CT scans to construct the predictive models (LUNAI-uCT model and LUNAI-eCT model), respectively. After the feature fusion of these two types of features, a fused model (LUNAI-fCT model) was constructed. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. SHapley Additive exPlanations analysis was used to quantify the impact of CT imaging features on model prediction. To gain insights into how our model makes predictions, we employed Gradient-weighted Class Activation Mapping to generate saliency heatmaps.Results The training and validation datasets included 113 patients from Center A at the 8:2 ratio, and the test dataset included 112 patients (Center B n=73, Center C n=20, Center D n=19). In the test dataset, the LUNAI-uCT, LUNAI-eCT, and LUNAI-fCT models achieved AUCs of 0.762 (95% CI 0.654 to 0.791), 0.797 (95% CI 0.724 to 0.844), and 0.866 (95% CI 0.821 to 0.883), respectively.Conclusions By extracting deep learning features from contrast enhanced and non-contrast enhanced CT, we constructed the LUNAI-fCT model as an imaging biomarker, which can non-invasively predict pathological complete response in neoadjuvant immunochemotherapy for NSCLC.

Abstract Background Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown. Methods Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2. Results We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1). Conclusion BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC.

Abstract Metal–organic frameworks (MOFs) are a class of promising nanomaterials for atmospheric water harvesting (AWH), especially in arid remote areas. However, several challenges are still faced for practical applications because of the dissatisfied water adsorption/desorption properties in terms of the capability, kinetics, and stability. Herein, we report the facile synthesis of a nano‐sized octahedral nitrogen‐modified MOF‐801 that exhibits superior solar‐powered AWH performance using a custom‐made device, with a state‐of‐the‐art water harvesting ability up to 4.64LH2OkgMOFs−1 from air upon 12‐h test under a relative humidity (RH) of 30% and simulated sunlight irradiation. The nitrogen‐modified MOF‐801 with rapid sorption–desorption kinetics, uptakes 0.29gH2OgMOFs‐1 of water at 30% RH within 30 min and releases 90% of the captured water within 10 min under 1‐sun illumination. The success relies on N‐doping‐induced mixed‐linkers in the form of 2,3‐diaminobutanedioic acid and fumaric acid in the unique pore structures of the MOFs for rapid and high‐capacity water capture. The N‐doped MOF‐801 with water uptake capacity, fast adsorption kinetics, and cycle stability sheds light on the practical use of MOFs for effective solar‐powered water harvesting from droughty air.

ObjectivesTo investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC) using quantification of intratumoral heterogeneity from pre-treatment CT image.MethodsThis retrospective study included 178 patients with NSCLC who underwent NAIC at 4 different centers. The training set comprised 108 patients from center A, while the external validation set consisted of 70 patients from center B, center C, and center D. The traditional radiomics model was contrasted using radiomics features. The radiomics features of each pixel within the tumor region of interest (ROI) were extracted. The optimal division of tumor subregions was determined using the K-means unsupervised clustering method. The internal tumor heterogeneity habitat model was developed using the habitats features from each tumor sub-region. The LR algorithm was employed in this study to construct a machine learning prediction model. The diagnostic performance of the model was evaluated using criteria such as area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV).ResultsIn the training cohort, the traditional radiomics model achieved an AUC of 0.778 [95% confidence interval (CI): 0.688-0.868], while the tumor internal heterogeneity habitat model achieved an AUC of 0.861 (95% CI: 0.789-0.932). The tumor internal heterogeneity habitat model exhibits a higher AUC value. It demonstrates an accuracy of 0.815, surpassing the accuracy of 0.685 achieved by traditional radiomics models. In the external validation cohort, the AUC values of the two models were 0.723 (CI: 0.591-0.855) and 0.781 (95% CI: 0.673-0.889), respectively. The habitat model continues to exhibit higher AUC values. In terms of accuracy evaluation, the tumor heterogeneity habitat model outperforms the traditional radiomics model, achieving a score of 0.743 compared to 0.686.ConclusionThe quantitative analysis of intratumoral heterogeneity using CT to predict pCR in NSCLC patients undergoing NAIC holds the potential to inform clinical decision-making for resectable NSCLC patients, prevent overtreatment, and enable personalized and precise cancer management.

Abstract Background Continuous cropping challenges constrain the development of agriculture. Three main obstacles limit continuous cropping: autotoxicity of plant allelochemicals, deterioration of physicochemical characteristics of soil, and microflora imbalance. Plant-derived phenolic acids can cause autotoxicity, which is considered the main factor mediating continuous cropping obstacles. Reducing the phenolic acids in continuous cropping soils can decrease the autotoxicity of phenolic acids and ameliorate continuous cropping obstacles. Therefore, it is important to study the microbial resources that degrade allelochemical phenolic acids. Thus, the bacterial strain V4 that can degrade phenolic acids was isolated, identified, and genomically analyzed. Results Strain V4 isolated from strawberry soil using vanillic acid-mineral agar was identified as a Gram-negative short rod bacterium. Subsequent 16S rRNA phylogenetic analysis revealed that V4 clustered with members of the genus Sphingobium. The most closely related species were Sphingobium lactosutens DS20T (99% similarity) and Sphingobium abikonense NBRC 16140T (97.5% similarity). V4 also shared > 95% sequence similarity with other members of Sphingobium, so Sphingobium sp. V4 was named accordingly. Biochemical tests revealed that the biochemical characteristics of Sphingobium sp. V4 were similar to its most similar strains except for some properties. Sphingobium sp. V4 effectively degraded vanillic acid, ferulic acid, p-coumaric acid, p-hydroxybenzoic acid, and syringic acid. V4 grew best at the conditions of 30 °C, pH 6.0–7.0, and 0–0.05% NaCl. 500 mg/L vanillic acid was completely degraded by V4 within 24 h under the optimal conditions. Whole genome analysis showed that Sphingobium sp. V4 contained one chromosome and three plasmids. Two genes involved in vanillic acid degradation were found in the V4 genome: the gene encoding vanillate O-demethylase oxidoreductase VanB on the chromosome and the gene encoding vanillate monooxygenase on a large plasmid. The organization of vanillate catabolic genes differed from the adjacent organization of the genes, encoding vanillate o-demethylase VanA and VanB subunits, in Pseudomonas and Acinetobacter. Conclusions The isolated bacterium Sphingobium sp. V4 degraded multiple phenolic acids. Its properties and genome were further analyzed. The study provides support for further investigation and application of this phenolic acid-degrading microorganism to alleviate continuous cropping obstacles in agriculture.

ObjectiveTo describe epidemiological characteristics of newly reported human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients in Fujian province through constructing a HIV molecular transmission network for effective prevention and control of HIV infection. MethodsBlood samples were collected and HIV RNA were extracted from 1 136 newly reported antiretroviral therapy-naïve HIV/AIDS patients in Fujian province in 2020. With HIV subtype B primers, HIV gene sequences of the HIV/AIDS patients were obtained by reverse transcription PCR using a self-established genotypic drug resistance detection method. A molecular transmission network was constructed for the HIV/AIDS patients based on the analysis using HIV-TRACE. ResultsOf the 908 participants with valid HIV gene sequencing results, 763 (84.03%) were males; 697 (76.76%) were aged 20 – 59 years; 852 (93.83%) were infected via sexual transmission; 351 (38.66%) had low education (illiteracy or primary school education); and 426 (46.92%) were married. The predominant HIV genotypes for the participants were CRF07_ BC and CRF01_ AE, together accounting for 82.49% of the infections. Drug resistance was detected in 48 (5.3%) of the participants. Under the 1.5% gene distance threshold, 108 molecular transmission clusters were established for 377 (41.52%) of the participants, with the largest cluster of CRF01_ AE subtype, 23 cluster nodes, and 21 clusters having 4 or more nodes. The results of multivariate logistic regression analysis showed that the participants aged 60 years and older (odds ratio [OR] = 1.875, 95% confidence interval [95%CI]: 1.215 – 3.241), being infected with subtype CRF07_ BC (OR = 2.112, 95%CI: 1.632 – 3.211) or CRF01_AE (OR = 1.987, 95%CI: 1.411 – 3.645), and being married (OR = 1.713, 95%CI: 1.245 – 2.487) were more likely to enter a molecular transmission network; but the participants having drug resistance were less likely to enter a molecular transmission network (OR = 0.195, 95%CI: 0.134 – 0.326) compared to those not having drug resistance. ConclusionAmong HIV/AIDS patients in Fujian province, molecular transmission network-related HIV infection was prevalent and influence by multiple factors; drug resistance was also prevalent among antiretroviral therapy-naïve HIV/AIDS patients. The study results should be concerned in regional HIV/AIDS control and prevention.

Abstract Background SHARPIN (SHANK‐associated RH domain interactor) is a component of the linear ubiquitination complex that regulates the NF‐κB signaling pathway. To better understand the function of SHARPIN, we sought to establish a novel genetically engineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system. Methods A single‐guide ribonucleic acid targeting exon 1 of SHARPIN gene was designed and constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatal mutants were identified by genotyping. SHARPIN protein expression was detected using Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymic weights were measured, and organ coefficients were calculated. Histopathological examination of the spleen, liver, lung, small intestine, and esophagus was performed independently by a pathologist. The expression of lymphocytic markers and cytokines was evaluated using reverse transcriptase‐quantitative polymerase chain reaction. Results All the offspring harbored germline‐transmitted SHARPIN mutations. Compared with wild‐type hamsters, SHARPIN protein was undetectable in SHARPIN−/− hamsters. Spleen enlargement and splenic coefficient elevation were spotted in SHARPIN−/− hamsters, with the descent of MLNs and thymuses. Further, eosinophil infiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagi were obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless, the expression of CCR3, CCL11, Il4, and Il13 was upregulated in the esophagi. The expression of NF‐κB and phosphorylation of NF‐κB and IκB protein significantly diminished in SHARPIN−/− animals. Conclusions A novel SHARPIN KO hamster was successfully established using the CRISPR/Cas9 system. Abnormal development of secondary lymphoid organs and eosinophil infiltration in multiple organs reveal its potential in delineating SHARPIN function and chronic inflammation.

To explore the hydraulic coupling characteristics of rocks, triaxial compression tests on water-saturated sandstone under hydro-mechanical coupling were carried out using the MTS815 rock mechanics test system. The test confining pressures were 10, 20, 30 MPa. Under each confining pressure, according to the ratio of pore water pressure to confining pressure, the pore water pressure was set to seven levels, which are 0, 10%、20%、40%、60%、80% and 90%. Then, the influence of the confining pressure and pore water pressure on the mechanical parameters such as the elastic modulus and Poisson’s ratio of the sandstone was analyzed. The energy evolution characteristics of sandstone under hydro-mechanical coupling were discussed in terms of energy curves, characteristic energy parameters and energy change ratios. Finally, the variation patterns of peak and residual strength were analyzed and the applicability of the Mohr-Coulomb and Hoek-Brown criteria under hydro-mechanical coupling was discussed based on the effective stresses. The results show that: ① the peak strength, residual strength, and elastic modulus of water-saturated sandstone increase with the increase of confining pressure, and decrease with increasing pore water pressure. Poisson’s ratio decreases as the confining pressure increases and increases as the pore water pressure increases. ② Under hydro-mechanical coupling, sandstone mainly undergoes shear failure, and as the pore water pressure increases, hydraulic fracturing is significant and its damage becomes more intense. ③ Combined with the test data of the sandstone and the published literatures, the normalized strength attenuation equation of rock peak strength and residual strength under hydro-mechanical coupling is obtained with the ratio of pore water pressure to confining pressure as the characteristic parameter. The strength attenuation coefficient of rock residual strength is greater than that of peak strength. ④ The trend of energy evolution curves of sandstone is consistent, and its energy storage limitation, peak dissipated energy density and residual elastic energy density are positively correlated with confining pressure, and negatively correlated with pore water pressure. ⑤ The evolution law of peak strength and residual strength of rock under hydro-mechanical coupling are in accordance with the Mohr-Coulomb criterion and Hoek-Brown criterion. The effective internal friction angles corresponding to peak and residual rock strengths are less different, while the effective cohesion and Hoek-Brown criterion parameters corresponding to the peak strength are much greater than those corresponding to the residual strength.

Abstract Herbivores have evolved the ability to detoxify feed components through different mechanisms. The oligophagous silkworm feeds on Cudrania tricuspidata leaves (CTLs) instead of mulberry leaves for the purpose of producing special, high-quality silk. However, CTL-fed silkworms are found to have smaller bodies, slower growth and lower silk production than those fed mulberry leaves. Here, we show that the high content of prenylated isoflavones (PIFs) that occurred in CTLs is converted into glycosylated derivatives (GPIFs) in silkworm faeces through the silkworm gut microbiota, and this biotransformation is the key process in PIFs detoxification because GPIFs are found to be much less toxic, as revealed both in vitro and in vivo. Additionally, adding Bacillus subtilis as a probiotic to remodel the gut microbiota could beneficially promote silkworm growth and development. Consequently, this study provides meaningful guidance for silk production by improving the adaptability of CTL-fed silkworms.

Cryoablation, as a minimally invasive technology for the treatment of tumors, destroys target tumors with lethal low temperatures. It simultaneously releases a large number of tumor-specific antigens, pro-inflammatory cytokines, and nucleoproteins, known as “danger signals”, activating the body’s innate and adaptive immune responses. However, tumor cells can promote the inactivation of immune effector cells by reprogramming immune checkpoints, leading to the insufficiency of these antigens to induce an immune response capable of eradicating the tumor. Immune checkpoint blockers rejuvenate exhausted T cells by blocking immune checkpoints that induce programmed death of T cells, and are therefore considered a promising therapeutic strategy to enhance the immune effects of cryoablation. In this review, we provide a detailed explanation of the immunological mechanisms of cryoablation and articulate the theoretical basis and research progress of the treatment of cancer with cryoablation combined with immune checkpoint blockers. Preliminary data indicates that this combined treatment strategy exhibits good synergy and has been proven to be safe and effective.

Predicting the status of train delays, a complex and dynamic problem, is crucial for railway enterprises and passengers. This paper proposes a novel hybrid deep learning model composed of convolutional neural networks (CNN) and temporal convolutional networks (TCN), named the CNN + TCN model, for predicting train delays in railway systems. First, we construct 3D data containing the spatiotemporal characteristics of real-world train data. Then, the CNN + TCN model employs a 3D CNN component, which is fed into the constructed 3D data to mine the spatiotemporal characteristics, and a TCN component that captures the temporal characteristics in railway operation data. Furthermore, the characteristic variables corresponding to the two components are selected. Finally, the model is evaluated by leveraging data from two railway lines in the United Kingdom. Numerical results show that the CNN + TCN model has greater accuracy and convergence performance in train delay prediction.

AbstractObjectives: A new method was introduced using a smartphone’s integrated inclinometer for rapid measurement of sagittal cervical parameters. The present study aims to compare the validity and reliability of the proposed method.Methods: We retrospectively reviewed 120 patients with cervical spondylosis treated at our hospital. The C0-2 Cobb angle, C2-7 Cobb angle, T1-slope (T1S), and neck tilt (NT) were selected as representative sagittal angles for this study. Two methods, the smartphone’s integrated inclinometer and picture archiving and communication system (PACS), were used to measure these four representative angles. Validity, reliability, and measurement times were recorded and compared.Results: The representative parameters (C0-2 Cobb angle, C2-7 Cobb angle, T1S, and NT), the ICC was 0.957 (0.939–0.970), 0.971 (0.958–0.979), 0.974 (0.963–0.982) and 0.949 (0.927–0.964) for validity respectively. For the aforementioned representative parameters, the ICC values were 0.972 (0.960–0.980), 0.979 (0.969–0.985), 0.972 (0.959–0.980), 0.942 (0.917–0.959) for intraobserver reliability respectively. For the representative parameters mentioned above, the ICC values were 0.947 (0.926–0.963), 0.964 (0.949–0.975), 0.956 (0.938-0.969), 0.916 (0.881–0.940) for interobserver reliability respectively. For the validity of the representative parameters mentioned above, the Bland-Altman plot displayed a mean difference of 0.2, 0.1, 0.1, and 0.4°with a 95% CI of 4.3, 4.5, 3.4, and 4.1°, respectively. The measurement by smartphone’s integrated inclinometer (46.31 ± 3.99 s) was significantly quicker than that by PACS (69.48 ± 3.25 s) according to independent-samples T test (p

Highlights Two series of terpolymers with improved photostability were realized by the introduction of appropriate ratio of antioxidant butylated hydroxytoluene unit containing side chains. All-polymer solar cells and organic photodetectors (OPDs) with these terpolymers as both donors and acceptors have been prepared with simultaneously improved efficiency and stability. A feasible approach to develop terpolymers with antioxidant efficacy for improving the lifetime of organic solar cells and OPDs is proposed.

Objectives To analyze conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in patients with secondary hyperparathyroidism (SHPT) and to evaluate the clinical-ultrasonographic feature based model for predicting the severity of SHPT. Methods From February 2016 to March 2021, a total of 59 patients (age 51.3 ± 11.7 years, seCr 797.8 ± 431.7 μmol/L, iPTH 1535.1 ± 1063.9 ng/L) with SHPT (including 181 parathyroid glands (PTGs)) without the history of intact parathyroid hormone (iPTH)-reducing drugs using were enrolled. The patients were divided into the mild SHPT group (mSHPT, iPTH

Innovation is a crucial factor for hidden champions to gain a competitive edge and foster organizational growth. This study focuses on Chinese-listed hidden champion firms between 2010 and 2019 and examines the impact of innovation heterogeneity on their growth. The study explores the impact of different types of innovation, including overall innovation, product innovation, and process innovation, and their interaction effects on the growth of hidden champions. The study also investigates the mediating role of the degree of specialization, which refers to the extent to which a firm focuses on a particular area of expertise. Furthermore, the potential of blockchain technology in advancing a sustainable energy future is becoming increasingly apparent. By enabling the creation of decentralized energy markets, blockchain can facilitate the integration of renewable energy sources, such as solar and wind power, into the grid. This can help to reduce carbon emissions and promote the transition to a low-carbon economy. The results of the study indicate that innovation, including overall innovation, product innovation, and process innovation, is significant for hidden champions’ growth. Moreover, the study reveals that product innovation and process innovation have complementary effects on the growth of hidden champions. The degree of specialization also plays a mediating role between different types of innovation and hidden champions’ growth. The results of this study provide empirical evidence to improve the growth of hidden champions from the perspective of enterprise innovation. By focusing on different types of innovation and understanding their complementary effects, firms can develop a more comprehensive innovation strategy that can enhance their growth potential. Moreover, the mediating role of degree of specialization highlights the importance of aligning innovation efforts with a firm’s core competencies to achieve sustained growth. This study contributes to the literature on hidden champions by shedding light on their innovation strategies and their impact on firm growth.

The utilization of gypsum mine goaf (GMG) for strategic oil reserves can realize the coordinated development of mining and oil storage. However, the variation in mechanical and permeability characteristics of gypsum rock under the action of crude oil erosion is not clear. At the same time, the deformation of gypsum rock caused by crude oil erosion will pose a threat to wellbore integrity. In this paper, a series of tests were carried out on gypsum rock before and after crude oil immersion to explore the effect of crude oil erosion on the mechanical and permeability characteristics of gypsum rock. The results show that crude oil soaking enhances the plastic deformation ability of gypsum rock. After soaking, the cohesion of gypsum rock increases by 14%, but the internal friction angle decreases by 7.2%. During the soaking process, crude oil invades the pores of gypsum rock, which can reduce the value of gypsum rock by 10−20 m2. Crude oil immersion enhances the deformation resistance of gypsum rock surrounding rock and significantly reduces the permeability, which is conducive to the stability and sealing of gypsum rock goaf during oil storage. The research results are helpful in deepening the understanding of using GMG technology to construct crude oil storage and provide inspiration for the study of the influence of gypsum rock deformation on wellbore integrity under crude oil erosion.

Abstract We introduced a novel method based on the iPhone’s intrinsic photo edit function to measure sagittal parameters of the cervical spine. This study aimed to assess the validity of this new method compared with the picture archiving and communication system (PACS) method (the gold standard) and to test the reliability of this novel technique. One hundred consecutive patients admitted to our hospital diagnosed with cervical spondylotic myelopathy or cervical spondylotic radiculopathy were retrospectively reviewed. Four angles, including the C0-2 Cobb angle, C2-7 Cobb angle, T1S and neck tilt (NT), were assessed by iPhone and PACS. The validity and reliability were evaluated, and the time taken by both methods was compared. The ICCs of the validity of the C0-2 Cobb angle, C2-7 Cobb angle, T1S and NT were 0.960, 0.976, 0.980 and 0.946, respectively. The ICCs of the intraobserver reliability of the C0-2 Cobb angle, C2-7 Cobb angle, T1S and NT were 0.966, 0.983, 0.971 and 0.951, respectively. The ICCs of the interobserver reliability of the C0-2 Cobb angle, C2-7 Cobb angle, T1S and NT were 0.953, 0.972, 0.957 and 0.929, respectively. The Bland‒Altman plot of validity of the four angles revealed mean differences of 0.3, 0.2, 0.1, and 0.1 degrees with 95% CIs of 4.1, 4.1, 2.9, and 4.3 degrees, respectively. The iPhone measurement time (58.55 ± 4.17 s) was significantly less than that by the PACS (70.40 ± 2.92 s) when compared by the independent-samples T test (P

Abstract Background The lack of a satisfactory strategy for postoperative pain management significantly impairs the quality of life for many patients. However, existing nanoplatforms cannot provide a longer duration of nerve blockage with intensity-adjustable characteristics under imaging guidance for clinical applications. Results To overcome this challenge, we proposed a biocompatible nanoplatform that enables high-definition ultrasound imaging-guided, intensity-adjustable, and long-lasting analgesia in a postoperative pain management model in awake mice. The nanoplatform was constructed by incorporating perfluoropentane and levobupivacaine with red blood cell membranes decorated liposomes. The fabricated nanoplatform can achieve gas-producing and can finely escape from immune surveillance in vivo to maximize the anesthetic effect. The analgesia effect was assessed from both motor reactions and pain-related histological markers. The findings demonstrated that the duration of intensity-adjustable analgesia in our platform is more than 20 times longer than free levobupivacaine injection with pain relief for around 3 days straight. Moreover, the pain relief was strengthened by repeatable ultrasound irradiation to effectively manage postoperative pain in an intensity-adjustable manner. No apparent systemic and local tissue injury was detected under different treatments. Conclusion Our results suggest that nanoplatform can provide an effective strategy for ultrasound imaging-guided intensity-adjustable pain management with prolonged analgesia duration and show considerable transformation prospects.

Cracks affect the strength of rock masses and eventually threaten their stability in engineering. In order to study the fracture characteristics and mechanical properties of cracked rocks, uniaxial compression tests of pre-cracked granite samples with a central circular through hole were carried out by using MTS816 rock mechanics testing system. The inclination angles of different pre-cracks are 0°, 15°, 30°, 45°, 60°, 75°, and 90° respectively, and the influence of the crack stop hole near the crack tip on the failure behavior of pre-cracked samples is also considered. The results indicate that, compared with the intact sample, the peak strength of pre-cracked samples decreases significantly and is related to the pre-crack inclination angle. The failure mode of the sample varies with the pre-crack inclination angle, and the crack stop hole near the crack tip also has a certain influence on the crack growth to a certain extent. However, in terms of failure mode and its transformation law, the influence of central circular through hole and crack stop hole can be ignored. Generally speaking, the larger the inclination angle of the pre-crack, the more the total energy required for failure of the sample, and the more the stored elastic strain energy. Before the peak strength, the elastic strain energy of the sample is greater than the dissipated energy, after the peak strength, the dissipated energy gradually exceeds the elastic strain energy due to energy conversion. It is found that the pre-crack reduces the energy storage capacity of the sample, and the total energy is ultimately dominated by sample integrity. The dissipated energy rate increases first, then decreases, and finally increases again, the inflection points are the end of micro-crack closure and the peak strength, respectively. The crack stop hole changes the law of energy evolution to a certain extent, which can improve the ability of rocks to accumulate energy when designed at an appropriate position, so as to improve its load-bearing capacity in a certain range. The results display the mechanical properties of pre-cracked granite samples under uniaxial compression and are conducive to its application in engineering.

Abstract Background Deacetylation of histones by histone deacetylase 3 (HDAC3) acts importantly in modulating apoptosis, DNA damage and cellular progression. Herein, we aimed to unravel the functional role of HDAC3 in a lethal disease, esophageal squamous cell carcinoma (ESCC). Methods The expression of HDAC3 in clinically collected ESCC tissues was determined by RT-qPCR and immunohistochemistry. As revealed from bioinformatics analysis, the putative relations between HDAC3 and microRNA-494 (miR-494) and between miR-494 and transforming growth factor beta (TGFβ)-inducing factor 1 (TGIF1) were further verified by chromatin immunoprecipitation and dual-luciferase reporter gene assay. Functional roles of shRNA-mediated depletion of HDAC3, miR-494 mimic and overexpressed TGIF1 were explored by gain- and loss-of-function assays with regard to ESCC cell biological behaviors. A nude mouse model of ESCC was developed for in vivo validation. Results HDAC3 was highly expressed in ESCC tissues, suggestive of poor prognosis while TGIF1 was upregulated and miR-494 was downregulated. Mechanistic investigation revealed that HDAC3 inhibited miR-494 expression and TGIF1 was a direct target of miR-494. Furthermore, silencing HDAC3 or overexpressing miR-494 was demonstrated to suppress aggressive phenotypes of ESCC cells both in vitro through the activated TGFβ signaling pathway and in vivo, while TGIF1 overexpression induced opposite results. Conclusion Collectively, our findings provided demonstration regarding the oncogenic property of HDAC3 in ESCC via the miR-494/TGIF1/TGFβ axis.

Abstract Lymph node metastasis, the leading cause of mortality in esophageal squamous carcinoma (ESCC) with a highly complex tumor microenvironment, remains underexplored. Here, the transcriptomes of 85 263 single cells are analyzed from four ESCC patients with lymph node metastases. Strikingly, it is observed that the metastatic microenvironment undergoes the emergence or expansion of interferon induced IFIT3+ T, B cells, and immunosuppressive cells such as APOC1+APOE+ macrophages and myofibroblasts with highly expression of immunoglobulin genes (IGKC) and extracellular matrix component and matrix metallopeptidase genes. A poor‐prognostic epithelial‐immune dual expression program regulating immune effector processes, whose activity is significantly enhanced in metastatic malignant epithelial cells and enriched in CD74+CXCR4+ and major histocompatibility complex (MHC) class II genes upregulated malignant epithelia cells is discovered. Comparing with primary tumor, differential intercellular communications of metastatic ESCC microenvironment are revealed and furtherly validated via multiplexed immunofluorescence and immunohistochemistry staining, which mainly rely on the crosstalk of APOC1+APOE+ macrophages with tumor and stromal cell. The data highlight potential molecular mechanisms that shape the lymph‐node metastatic microenvironment and may inform drug discovery and the development of new strategies to target these prometastatic nontumor components for inhibiting tumor growth and overcoming metastasis to improve clinical outcomes.

Residual lesions and undetectable metastasis after insufficient radiofrequency ablation (iRFA) are associated with earlier new metastases and poor survival in cancer patients, for induced aggressive tumor phenotype and immunosuppression. Programmed cell death protein 1(PD-1) blockade has been reported to enhance the radiofrequency ablation-elicited antitumor immunity, but its ability to eliminate incompletely ablated residual lesions has been questioned. Here, we report a combined treatment modality post iRFA based on integrating an oxygen self-enriching nanodrug PFH-Ce6 liposome@O2 nanodroplets (PCL@O2)-augmented noninvasive sonodynamic therapy (SDT) with PD-1 blockade. PCL@O2 containing Ce6 as the sonosensitizer and PFH as O2 reservoir, was synthesized as an augmented SDT nanoplatform and showed increased ROS generation to raise effective apoptosis of tumor cells, which also exposed more calreticulin to induce stronger immunogenic cell death (ICD). Combining with PD-1 blockade post iRFA, this optimized SDT induced a better anti-tumor response in MC38 tumor bearing mouse model, which not only arrested residual primary tumor progression, but also inhibited the growth of distant tumor, therefore prolonging the survival. Profiling of immune populations within the tumor draining lymph nodes and tumors further revealed that combination therapy effectively induced ICD, and promoted the maturation of dendritic cells, tumor infiltration of T cells, as well as activation of cytotoxic T lymphocytes. While iRFA alone could result in an increase of regulatory T cells (Tregs) in the residual tumors, SDT plus PD-1 blockade post iRFA reduced the number of Tregs in both primary and distant tumors. Moreover, the combined treatment could significantly initiate long-term immune memory, manifesting as elevated levels of CD8+ and CD4+ central memory cells. Therefore, this study establishes the preclinical proof of concept to apply oxygen self-enriching SDT to augment cancer immunotherapy after iRFA.

Eutectogels (Egels) are an emerging class of soft ionic materials outperforming traditional temperature-intolerant hydrogels and costly ionogels. Due to their excellent elasticity, non-volatile nature, and adhesion properties, Egels are attracting a great deal of interest in the biomedical space. Herein, we report the first example of adhesive Egels loading drug nanocrystals (Egel-NCs) for controlled delivery to mucosal tissues. These soft materials were prepared using gelatin, glycerine, a deep eutectic solvent (DES) based on choline hydrochloride and glycerol, and nanocrystallised curcumin, a model drug with potent antimicrobial and anti-inflammatory activities. We first explored the impact of the biopolymer concentration on the viscoelastic and mechanical properties of the networks. Thanks to the dynamic interactions between gelatin and the DES, the Egel showed excellent stretchability and elasticity (up to ≈160%), reversible gel-sol phase transition at mild temperature (≈50 ​°C), 3D-printing ability, and good adhesion to mucin protein (stickiness ≈40 ​kPa). In vitro release profiles demonstrated the ability of the NCs-based Egel to deliver curcumin for up to four weeks and deposit significantly higher drug amounts in excised porcine mucosa compared to the control cohort. All in all, this study opens new prospects in designing soft adhesive materials for long-acting drug delivery and paves the way to explore novel eutectic systems with multiple therapeutic applications.

Abstract Background Esophageal carcinogenesis is a multifactorial process in which genetic and environmental factors interact to activate intracellular signals, leading to the uncontrolled survival and growth of esophageal squamous cell carcinoma (ESCC) cells. The intracellular pathways of ESCC cells could be regulated by proteinase activated-receptors (PARs), which are comprised of four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4). Therefore, the function and possible mechanism of PAR1 and PAR4 in the progression of ECSS were explored in our study. Methods First, we detected the expression levels of PAR1 and PAR4 in 27 cases of ESCC specimens and cell lines by RT-qPCR, IHC and western blot. Meanwhile, the correlation between PAR1/PAR4 expression levels, clinicopathological characteristics, and disease free survival was analyzed. Then, we constructed PAR1/PAR4 knockdown cell models and investigated the role of PAR1/PAR4 knockdown on the proliferation, apoptosis, changes of calcium flow, and metastasis of ESCC cells via MTT, flow cytometry, transwell and wound healing assays in vitro. Further, an experimental metastasis model in vivo was established to explore the role of stable PAR1/PAR4 knockdown on the growth and metastasis of ESCC cells. Finally, the role of nSMase2 in the activation of NF-κB induced by PAR4 and the role of NF-κB and STAT3 signaling pathways in the PAR1/PAR4-mediated tumor promoting or suppressive functions were measured by immunoprecipitation, western blot and immunofluorescence assays. Results First, the integrated results demonstrated the expression levels of PAR1 and PAR4 are inversely proportional in ESCC. PAR1 potently enhanced tumor growth and metastasis, while PAR4 had an inhibitory effect. Further, the co-activation of STAT3 and NF-κB was involved in the PAR1 activation-induced tumor promoting effect, while only NF-κB participated in the PAR4 activation-induced tumor inhibitory effect in ESCC. To be specific, FAK/PI3K/AKT/STAT3/NF-κB signaling mediated PAR1 activation-induced tumor promoting effect and nSMase2/MAPK/NF-κB signaling mediated PAR4 activation-induced tumor inhibitory effect. Conclusions Overall, the study has provided new insights into the potential implication of PAR1 and PAR4 in the pathogenesis of ESCC. Besides, FAK/PI3K/AKT/STAT3/NF-κB and nSMase2/MAPK/NF-κB pathways may be novel targets for regulating tumor growth and metastasis in ESCC patients.

Abstract. The diagnosis of allergic bronchopulmonary mycosis (ABPM) is usually made on clinical, serologic, and roentgenographic findings. However, the indicators in such diagnostic criteria still lack specificity, which results in a high rate of misdiagnosis. A 47-year-old woman was diagnosed with “tuberculosis” or “pneumonia” for 10 years and after thoracoscopic right upper lung resection the following chest CT showed right lung atelectasis. Brown sputum was seen in the right bronchus via bronchoscopy. Reviewing the surgical pathology specimen, the bronchi were found to be generally cystic dilated, and a large amount of mucus was retained and formed a mucus plug. The final diagnosis of the case was ABPM. The current diagnostic criteria of ABPM do not emphasize the role of bronchoscopy and pathological examination, but bronchoscopy and pathological examination still have important value for some atypical cases with suspected ABPM.

At the beginning of the 21st century, micro-nano processing technology has developed rapidly, and research on wearable electronic devices has exploded. In particular, flexible thermoelectric materials and thermoelectric generators (TEGs) that have stretchable or foldable properties have been widely studied. Textile-based thermoelectric materials are more suitable for use on the human body than are film or block types of devices, and they are accordingly favoured for wearable smart devices. The design idea of textile thermoelectric materials include the preparation of thermoelectric fibres, textiles, fabric-based films and some novel methods, like using three-dimensional modules to become two-dimensional fabrics by a weaving method, which not to rely something as a base for TE modules. Investigators are thus gaining opportunities to make comfortable and effective fabric TEGs using a wider variety of materials. This article briefly introduces the common methods used to produce textile TEGs. The opportunities and challenges of fabric TEGs are discussed at the end.

With the growing demands of human beings, sanitary landfill, along with the increase in landfill depth and leachate water pressure, has put forward new and higher requirements for the impermeable layer. In particular, it is required to have a certain adsorption capacity of harmful substances from the perspective of environmental protection. Hence, the impermeability of polymer bentonite–sand mixtures (PBTS) at different water pressure and the adsorption properties of polymer bentonite (PBT) on contaminants were investigated through the modification of PBT using betaine compounded with sodium polyacrylate (SPA). It was found that the composite modification of betaine and SPA could reduce the average particle size of PBT dispersed in water (reduced to 106 nm from 201 nm) and enhance the swelling properties. As the content of SPA increased, the hydraulic conductivity of PBTS system decreases and the permeability resistance improves, while the resistance to external water pressure increases. It is proposed a concept of the potential of osmotic pressure in a constrained space to explain the impermeability mechanism of PBTS. The potential of osmotic pressure obtained by linear extrapolation of the trendline of colloidal osmotic pressure versus mass content of PBT could represent the external water pressure that the PBT resist. Additionally, the PBT also has a high adsorption capacity for both organic pollutants and heavy metal ions. The adsorption rate of PBT was up to 99.36% for phenol; up to 99.9% for methylene blue; and 99.89%, 99.9%, and 95.7% for low concentrations of Pb2+, Cd2+, and Hg+, respectively. This work is expected to provide strong technical support for the future development in the field of impermeability and removal of hazardous substances (organic and heavy metals).

Highlights Shape memory self-soldering tape used as conductive interconnecting material. Perfect shape and conductivity memory performance and anti-fatigue performance. Reversible strong-to-weak adhesion switched by temperature. Abstract With practical interest in the future applications of next-generation electronic devices, it is imperative to develop new conductive interconnecting materials appropriate for modern electronic devices to replace traditional rigid solder tin and silver paste of high melting temperature or corrosive solvent requirements. Herein, we design highly stretchable shape memory self-soldering conductive (SMSC) tape with reversible adhesion switched by temperature, which is composed of silver particles encapsulated by shape memory polymer. SMSC tape has perfect shape and conductivity memory property and anti-fatigue ability even under the strain of 90%. It also exhibits an initial conductivity of 2772 S cm−1 and a maximum tensile strain of ~ 100%. The maximum conductivity could be increased to 5446 S cm−1 by decreasing the strain to 17%. Meanwhile, SMSC tape can easily realize a heating induced reversible strong-to-weak adhesion transition for self-soldering circuit. The combination of stable conductivity, excellent shape memory performance, and temperature-switching reversible adhesion enables SMSC tape to serve two functions of electrode and solder simultaneously. This provides a new way for conductive interconnecting materials to meet requirements of modern electronic devices in the future.

Dilated cardiomyopathy (DCM) is defined by left ventricular (or biventricular dilation) and systolic dysfunction, which eventually develops into congestive heart failure and arrhythmia. Vinculin is a membrane-associated protein, which functions to transmit contractile force. Defects in vinculin have been reported to be associated with DCM and hypertrophic cardiomyopathy. A human induced pluripotent stem cell (iPSC) line (ZZUNEUi026-A) was generated from a DCM patient carrying heterozygous Vinculin mutant (c.A625 > T; p.Met209 > Leu). The cell line was derived from peripheral blood mononuclear cells by nonintegrative Sendai virus. ZZUNEUi026-A showed pluripotency markers and normal karyotype, and it could differentiate into three germ layers in vitro.

Background: Deoxythymidylate kinase (DTYMK) serves as a pyrimidine metabolic rate-limiting enzyme that catalyzes deoxythymidine monophosphate (dTMP) to generate deoxythymidine diphosphate (dTDP). It remains unclear whether DTYMK expression has the potential to predict outcome and immune cell infiltration in cancers.Methods: DTYMK expression profile was analyzed using Oncomine, TIMER, GEPIA and UALCAN databases. The influence of DTYMK on immune infiltration was examined using TIMER and TISIDB databases. DTYMK interactive gene hub and co-expressing genes were obtained and analyzed by STRING and Linkedomics, respectively. The relationship between DTYMK expression and patient prognosis was validated using GEPIA, Kaplan-Meier plotter, and PrognoScan databases. The functions of DTYMK in cancer cells were also biologically validated in vitro.Results: DTYMK expression was elevated in tumor tissues compared with their control counterparts. DTYMK expression varied in different stages and discriminatorily distributed in different immune and molecular subtypes. Higher expression of DTYMK predicted worse outcome in several cancer types such as liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD). High DTYMK expression was positively or negatively correlated with immune cell infiltration, including B cell, CD8+ cell, CD4+ T cell, macrophage, neutrophil and dendritic cell, depending on the type of cancers. Additionally, DTYMK co-expressing genes participated in pyrimidine metabolism as well as in T helper cell differentiation in LIHC and LUAD. In vitro, knockdown of DTYMK suppressed cell migration of liver and lung cancer cells.Conclusion: DTYMK might be taken as an useful prognostic and immunological marker in cancers and further investigation is warrented.

Fermentation is a promising method to improve the utilization of soybean meal (SM) by fish, and strain is the core of fermentation process. In this study, the effects of Lactobacillus paracasei fermentation on the SM quality were investigated. Also, an 8-week feeding trial was conducted to compare the performance of SM and L. paracasei fermented SM (LPFSM) in diets for turbot. Juvenile turbots (13.50 ± 0.13 g) were randomly divided into nine treatments fed on diets with 0% (FM, control), 15% (S15/L15), 30% (S30/L30), 45% (S45/L45), and 60% (S60/L60) of fishmeal protein replaced by SM or LPFSM respectively. The results showed that fermentation remarkably increased the lactic acid and decreased the anti-nutritional factors in SM. Furthermore, fishmeal could be replaced by SM up to 30% or by LPFSM up to 45% based on the growth performance. Typical groups (FM, S45, and L45) with significant differences in growth were selected for further analysis. Reduced villus height and widened lamina propria were observed in the S45 group, while no significant pathological symptom was found in the L45 group. The mRNA levels of the apoptosis-related genes (bax, p53, and caspase3) and tight junction-related gene (tricellulin) in the S45 group were significantly up-regulated or down-regulated, respectively, while the L45 group remained similar to the FM group. The mRNA levels of tight junction-related genes (zo-1 and occludin) were significantly down-regulated in both S45 and L45 groups compared to the FM group. Furthermore, dietary LPFSM modified the intestinal microbiota by regulating the dominant bacterial phyla (Proteobacteria, Firmicutes, and Actinobacteria) and genera (Cobetia, Pseudomonas, and Lactobacillus), and making the overall microbiota profile more coherent with FM-fed fish. Collectively, L. paracasei fermentation significantly improved the SM quality, and fishmeal could be replaced by LPFSM up to 45% without adverse effects on growth and intestinal health of turbot.

Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in esophageal cancer tissues and cells and then linked its low expression to cancer progression. Bioinformatic analysis predicted KDM5B as a target gene of let-7i, which was confirmed by a dual-luciferase reporter assay. Loss- and gain-of function approaches were adopted to examine the interactions of let-7i, KDM5B, SOX17, and GREB1 in vitro and in vivo. Overexpression of let-7i suppressed esophageal cancer cell proliferation and invasion and promoted apoptosis. Mechanistic investigation showed that let-7i targeted and inhibited KDM5B expression, whereas KDM5B enhanced H3K4me3 at the SOX17 promoter region. Overexpression of let-7i suppressed the expression of GREB1 in esophageal cancer cells by regulating the KDM5B/SOX17 axis in vivo and in vitro. Taken together, our findings reveal the tumor-suppressive properties of let-7i in esophageal cancer in association with an apparent KDM5B-dependent SOX17/GREB1 axis. This study offers a potential prognostic marker and therapeutic target for esophageal cancer.

Abstract Background Liao ning virus (LNV) is a member of the genus Seadornavirus, family Reoviridae and has been isolated from kinds of vectors in Asia and Australia. However, there are no systematic studies describe the molecular genetic evolution and migration of LNVs. With the development of bioinformatics, viral genetic data combining the information of virus isolation time and locations could be integrated to infer the virus evolution and spread in nature. Methods Here, a phylogenetic and phylogeographic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on the LNVs isolated from a variety of vectors during 1990–2014 to identify the evolution and migration patterns of LNVs. Results The results demonstrated that the LNV could be divided into 3 genotypes, of which genotype 1 mainly composed of LNVs isolated from Australia during 1990 to 2014 and the original LNV strain (LNV-NE97–31) isolated from Liaoning province in northern China in 1997, genotype 2 comprised of the isolates all from Xinjiang province in western China and genotype 3 consisted the isolates from Qinghai and Shanxi province of central China. LNVs emerged about 272 years ago and gradually evolved into three lineages in the order genotype 1, genotype 2 and genotype 3. Following phylogeographic analysis, it shows genotype 1 LNVs transmitted from Australia (113°E-153°E,10°S-42°S) to Liaoning province (118°E-125°E,38°N-43°N) in Northeast Asian continent then further spread across the central part of China to western China (75°E-95°E,35°N-50°N). Conclusion LNVs were initially isolated from Liaoning province of China in the Northeast Asia, however, the present study revealed that LNVs were first appeared in Australia in the South Pacific region and transmitted to mainland China then rapidly spread across China and evolved three different genotypes. The above results suggested that LNV had the characteristics of long-distance transmission and there were great genetic diversity existed in the LNV population. Notably, current information of 80 strains of LNVs are limited. It is of great importance to strengthen the surveillance of LNVs to explore its real origin in nature and monitoring of the LNVs’ population variation and maintain vigilance to avoid LNV breaking through the species barrier and further clarify its relationship to human and animal infection.

Ischemic tolerance in the brain can be induced by transient limb ischemia, and this phenomenon is termed remote ischemic preconditioning (RIPC). It still remains elusive how this transfer of tolerance occurs. Exosomes can cross the blood-brain barrier, and some molecules may transfer neuroprotective signals from the periphery to the brain. Serum miRNA-126 is associated with ischemic stroke, and exosomal miRNA-126 has shown protective effects against acute myocardial infarction. Therefore, this study aims to explore whether exosomal miRNA-126 from RIPC serum can play a similar neuroprotective role. Exosomes were isolated from the venous serum of four healthy young male subjects, both before and after RIPC. Exosomal miRNA-126 was measured by real-time PCR. The miRNA-126 target sequence was predicted by bioinformatics software. SH-SY5Y neuronal cells were incubated with exosomes, and the cell cycle was analyzed by flow cytometry. The expression and activity of DNA methyltransferase (DNMT) 3B, a potential target gene of miRNA-126, were examined in SH-SY5Y cells. The cell viability of SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD) was also investigated. To confirm the association between miRNA-126 and DNMT3B, we overexpressed miRNA-126 in SH-SY5Y cells using lentiviral transfection. miRNA-126 expression was upregulated in RIPC exosomes, and bioinformatics prediction showed that miRNA-126 could bind with DNMT3B. DNMT levels and DNMT3B activity were downregulated in SH-SY5Y cells incubated with RIPC exosomes. After overexpression of miRNA-126 in SH-SY5Y cells, global methylation levels and DNMT3B gene expression were downregulated in these cells, consistent with the bioinformatics predictions. RIPC exosomes can affect the cell cycle and increase OGD tolerance in SH-SY5Y cells. RIPC seems to have neuroprotective effects by downregulating the expression of DNMTs in neural cells through the upregulation of serum exosomal miRNA-126.

The inadequate consideration of livable rural spatial morphology in rural planning has impeded the further advancement of the rural social system, resulting in a challenge for rural residents to establish an appealing living experience that distinguishes itself from urban areas. This situation calls for an urgent exploration of livable spatial morphology based on human-centered principles, as well as an investigation of planning spatial morphology optimization mechanisms that consider ecological backgrounds and human settlement needs. In response to this issue, this study employs the theory of flow space and constructs a framework for the optimization of rural spatial methodology. By integrating ecological and sociological analysis methods, the study identifies the “flow” structure of spatial association in rural ecosystems through ecological network analysis, and identifies the “flow” structure of behavioral association in rural human systems through social network analysis. Based on these findings, the complex network morphologies are evaluated and screened. To test the effectiveness of this framework, the study examines the spatial morphology of four planning options through case empirical analysis in Zepan Village, Hebei Province, China. The research results demonstrate that the framework can help achieve the goal of optimizing rural spatial morphology, improve existing planning practices that prioritize single plans and disregard the selection of multiple plans, and serve as an effective tool to aid planners in tackling complex planning problems by balancing scientific principles and empirical values.

Objective. Observational studies show the correlation between thyroid dysfunction and risk of venous thromboembolism. However, the causal effects remain uncertain. Our study was conducted to evaluate whether thyroid function and dysfunction were causally linked to the risk of venous thromboembolism. Methods. Publicly available summary data of thyrotropin (TSH) and free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained from the ThyroidOmics Consortium and the UK Biobank. With single nucleotide polymorphisms (SNPs) as instrumental variables, the casual effects of genetically predicted TSH and FT4 and hypo- and hyperthyroidism on venous thromboembolism outcome were estimated through Mendelian randomization analysis methods (inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode). Cochran’s Q test was performed to evaluate the heterogeneity and horizontal pleiotropy. Results. Our study selected 15 FT4-, 36 TSH-, 3 hyperthyroidism-, and 79 hypothyroidism-associated SNPs as instrumental variables. The IVW analysis results showed that the odds ratio of venous thromboembolism for hyperthyroidism was 1.124 (95% confidence interval: 1.019-1.240; p=0.019), demonstrating the casual effect of hyperthyroidism not FT4, TSH, and hypothyroidism on venous thromboembolism. No heterogeneity or horizontal pleiotropy was observed according to Cochran’s Q test. Conclusion. Our Mendelian randomization analysis supports the causal effect of hypothyroidism on risk of venous thromboembolism. There is no evidence that genetically predicted TSH, FT4, and hypothyroidism have casual effects on venous thromboembolism. Future studies should be conducted to elucidate the underlying pathophysiological mechanisms.

Dilated cardiomyopathy (DCM) is a nonischaemic heart muscle disease with structural and functional myocardial abnormalities. TTN truncating mutations are a common cause of DCM, occurring in ∼25% of familial cases of DCM and in 18% of sporadic cases. In this study, we generated a human induced pluripotent stem cell line ZZUNEUi023-A from peripheral blood mononuclear cells of a Kazakh DCM patient with the p. Arg26562Ter (c. 79684C>T) mutation in TTN using non-integrative Sendai virus. This cell line expressed pluripotency markers, showed normal male karyotype and could differentiate into all three germ layers in vitro.

Influenza epidemics cause considerable morbidity and mortality every year worldwide. Climate-driven epidemiological models are mainstream tools to understand seasonal transmission dynamics and predict future trends of influenza activity, especially in temperate regions. Testing the structural identifiability of these models is a fundamental prerequisite for the model to be applied in practice, by assessing whether the unknown model parameters can be uniquely determined from epidemic data. In this study, we applied a scaling method to analyse the structural identifiability of four types of commonly used humidity-driven epidemiological models. Specifically, we investigated whether the key epidemiological parameters (i.e., infectious period, the average duration of immunity, the average latency period, and the maximum and minimum daily basic reproductive number) can be uniquely determined simultaneously when prevalence data is observable. We found that each model is identifiable when the prevalence of infection is observable. The structural identifiability of these models will lay the foundation for testing practical identifiability in the future using synthetic prevalence data when considering observation noise. In practice, epidemiological models should be examined with caution before using them to estimate model parameters from epidemic data.

Abstract Non‐small cell lung cancer (NSCLC), the major type of lung cancer, becomes the greatest threat to the life of people. Growing evidence shows prostate androgen‐regulated transcript 1 (PART1) is considered as effective markers for prostate cancer, and has been shown to be associated with poor prognosis of NSCLC. However, the tumorigenic mechanism of PART1 in NSCLC remains to be investigated. In this study, we found that the expression of PART1 was robustly induced in NSCLC tissues and cell lines. Functional studies established that overexpression of PART1 could promote NSCLC cell proliferation, migration, and invasion, while interference of PART1 inhibited NSCLC progression. Our results also identified miR‐635 as a novel target of PART1, whose expression was inhibited by PART1 in NSCLC cell lines. Moreover, gain‐ and loss‐of‐function studies revealed that PART1 could sponge miR‐635 and increase the expression of Janus kinase (JAK) and signal transducer and activator of transcription proteins (STATs). Finally, we deciphered the molecular mechanism by which PART1 contributed to promotion of NSCLC cell progression via phosphorylation and activation of JAK‐STAT signaling pathway. The animal experiment further confirmed that interference of NSCLC could suppress in vivo tumorigenic ability of NSCLC with favorable pharmacological activity via inactivation of JAK‐STAT signaling pathway. In conclusion, our findings clarified the biologic significance of PART1/miR‐635/JAK‐STAT axis in NSCLC progression and provided novel evidence that PART1 may be a new potential therapeutic target for the treatment of NSCLC.