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Amidst the uncertainties of climate policy, investing in nuclear energy technology emerges as a sustainable strategy, fostering innovation in a critical sector, while simultaneously addressing urgent environmental concerns and managing budgetary dynamics. Our investigation inspects the asymmetric influence of climate policy uncertainty on nuclear energy technology in the top 10 nations with the highest nuclear energy R&D budgets (Germany, Japan, China, France, USA, UK, India, South Korea, Russia, and Canada). Previous studies adopted panel data methods to evaluate the linkage between climate policy uncertainty and nuclear energy technology. Nonetheless, these investigations overlooked the variability in this association across various countries. Conversely, this investigation introduces an innovative tool, ‘Quantile-on-Quantile’ to probe this connection merely for every economy. This methodology concedes for a more accurate evaluation, offering a holistic global perspective and delivering tailored insights for individual countries. The findings uncover that climate policy uncertainty significantly reduces nuclear energy technology budgets across multiple quantiles in most selected economies. Additionally, our results highlight the asymmetries in the correlations between our variables across the nations. These findings stress the need for policymakers to conduct thorough assessments and skillfully manage climate policy uncertainty and nuclear energy budgets.

Abstract Gossen’s First Law describes the law of diminishing marginal utility. This paper aims to further verify the proposed hypothesis that Gossen’s First Law also holds in the modeling for Demand Side Management (DSM) with a thorough heat pump case study. The proposed hypothesis states that in general the complexity-utility relationship in the field of DSM modeling could be represented by a diminishing marginal utility curve. On the other hand, in data based modeling, when utilizing a large dataset for validation, the data integrity is critical to the reliability of the results. However, the absence of partial time series data may occur during the measurement due to missing sensors or IT related issues. In this work, an extensive real-world open dataset of a ground source heat pump is utilized for the case study. In the raw data, one key variable namely the flow rate is missing. Thus, three different algorithms based on machine learning and deep learning architectures namely Random Forest (RF), Long Short-Term Memory (LSTM) and Transformer are applied to predict the flow rate by utilizing an open loop forecasting. The raw data are first pre-processed with a time interval of one hour and then used for training, validation and forecast. Furthermore, a modified persistence model as the baseline is also defined. The predicted flow rate using LSTM yields the lowest error of 7.47 $$\%$$ % nMAE and 10.56 $$\%$$ % nRMSE respectively. The forecast results are then utilized in the following step of modeling of a heat pump use case. With the introduced quantification method for complexity and a modified version for utility, we further verify the proposed hypothesis with a longer time horizon of 7 days.

Abstract Background Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. Results This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. Conclusions ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.

Abstract Scene text in natural images carries additional semantic information to aid in image classification. Existing methods lack full consideration of the deep understanding of the text and the visual text relationship, which results in the difficult to judge the semantic accuracy and the relevance of the visual text. This paper proposes image classification based on Cross modal Knowledge Learning of Scene Text (CKLST) method. CKLST consists of three stages: cross‐modal scene text recognition, text semantic enhancement, and visual‐text feature alignment. In the first stage, multi‐attention is used to extract features layer by layer, and a self‐mask‐based iterative correction strategy is utilized to improve the scene text recognition accuracy. In the second stage, knowledge features are extracted using external knowledge and are fused with text features to enhance text semantic information. In the third stage, CKLST realizes visual‐text feature alignment across attention mechanisms with a similarity matrix, thus the correlation between images and text can be captured to improve the accuracy of the image classification tasks. On Con‐Text dataset, Crowd Activity dataset, Drink Bottle dataset, and Synth Text dataset, CKLST can perform significantly better than other baselines on fine‐grained image classification, with improvements of 3.54%, 5.37%, 3.28%, and 2.81% over the best baseline in mAP, respectively.

Abstract Background The ectopic superior parathyroid in the tracheoesophageal groove and paraesophageal region is rare. Hyperparathyroidism results when these glands become hyperfunctioning. That may necessitate surgical intervention in the form of parathyroidectomy, which requires a transsternal or transthoracic approach due to a deeply seated mediastinal parathyroid gland. Minimally invasive strategies have emerged recently as an alternative approach with less morbidity. Case presentation We present a case of the paraesophageal ectopic parathyroid gland in the superior posterior mediastinum, which was successfully treated with thoracoscopic resection. Conclusion The current imaging tools improve the thoracoscopic management of mediastinal parathyroid glands. Video-assisted thoracoscopic surgery (VATS) can provide access and exposure to ectopic parathyroid adenoma with low morbidity and financial burden.

Abstract Minority Cultural Heritage (MCH) plays a crucial role in preserving human cultural and historical diversity. In Southwest China, there is a disparity between the abundance of ethnic minority cultural heritage resources and their inadequate protection and development. However, limited by interdisciplinary barriers, research into the distribution patterns of varied MCH in this area remains unexplored, making an initial step towards comprehensive preservation. The study investigates the relationship between MCH distribution and its association with factors of geography, climate, transportation, economics, and demographics, utilizing spatial geographic analysis, Geodetector methods, and social network analysis. The results indicate the following: (1) The distribution of 483 national-level MCH in Southwest China exhibits clustering, with a higher concentration in the southern regions. Honghe Prefecture, Dali Prefecture, and Qiandongnan Prefecture serve as the core areas with high MCH density, accounting for 47.2% of the total concentration. (2) All three categories of MCH show cohesive distribution patterns. cultural heritage clusters in the northern to southeastern regions of Yunnan Province, intangible cultural heritage clusters in the southeastern to southern regions of Guizhou Province, and agricultural cultural heritage clusters in the northern region of Yunnan Province. (3) The distribution of MCH among different ethnic minorities demonstrates polarization. The Yi and Tibetan ethnic groups have a higher quantity and diversity of MCH, while the Qiang, Lisu, and Jingpo ethnic groups have relatively fewer resources. (4) Single-factor analysis reveals that natural factors like the proportion of mountainous areas, river density, and annual average sunshine, as well as human factors like the proportion of minority population, urbanization rate, and road mileage, have the strongest explanatory power for the distribution of MCH. Furthermore, the interaction between these factors and others enhances the explanatory power for the distribution of MCH in Southwest China. This study provides scientific evidence for the assessment, protection, and sustainable development of MCH.

Abstract Plant growth and development can be significantly impacted by drought stress. Plants will adjust the synthesis and accumulation of secondary metabolites to improve survival in times of water constraint. Simultaneously, drought stress can lead to modifications in the DNA methylation status of plants, and these modifications can directly impact gene expression and product synthesis by changing the DNA methylation status of functional genes involved in secondary metabolite synthesis. However, further research is needed to fully understand the extent to which DNA methylation modifies the content of secondary metabolites to mediate plants’ responses to drought stress, as well as the underlying mechanisms involved. Our study found that in Eleutherococcus senticosus (E. senticosus), moderate water deprivation significantly decreased DNA methylation levels throughout the genome and at the promoters of EsFPS, EsSS, and EsSE. Transcription factors like EsMYB-r1, previously inhibited by DNA methylation, can re-bind to the EsFPS promotor region following DNA demethylation. This process promotes gene expression and, ultimately, saponin synthesis and accumulation. The increased saponin levels in E. senticosus acted as antioxidants, enhancing the plant’s adaptability to drought stress.

Abstract Purpose In VATS surgery, precise preoperative localization is particularly crucial when dealing with small-diameter pulmonary nodules located deep within the lung parenchyma. The purpose of this study was to compare the efficacy and safety of laser guidance and freehand hook-wire for CT-guided preoperative localization of pulmonary nodules. Methods This retrospective study was conducted on 164 patients who received either laser guidance or freehand hook-wire localization prior to Uni-port VATS from September 1st, 2022 to September 30th, 2023 at The First Affiliated Hospital of Soochow University. Patients were divided into laser guidance group and freehand group based on which technology was used. Preoperative localization data from all patients were compiled. The localization success and complication rates associated with the two groups were compared. The risk factors for common complications were analyzed. Results The average time of the localization duration in the laser guidance group was shorter than the freehand group (p

Abstract Introduction Inaccurate, untimely diagnoses of fundus diseases leads to vision-threatening complications and even blindness. We built a deep learning platform (DLP) for automatic detection of 30 fundus diseases using ultra-widefield fluorescein angiography (UWFFA) with deep experts aggregation. Methods This retrospective and cross-sectional database study included a total of 61,609 UWFFA images dating from 2016 to 2021, involving more than 3364 subjects in multiple centers across China. All subjects were divided into 30 different groups. The state-of-the-art convolutional neural network architecture, ConvNeXt, was chosen as the backbone to train and test the receiver operating characteristic curve (ROC) of the proposed system on test data and external test date. We compared the classification performance of the proposed system with that of ophthalmologists, including two retinal specialists. Results We built a DLP to analyze UWFFA, which can detect up to 30 fundus diseases, with a frequency-weighted average area under the receiver operating characteristic curve (AUC) of 0.940 in the primary test dataset and 0.954 in the external multi-hospital test dataset. The tool shows comparable accuracy with retina specialists in diagnosis and evaluation. Conclusions This is the first study on a large-scale UWFFA dataset for multi-retina disease classification. We believe that our UWFFA DLP advances the diagnosis by artificial intelligence (AI) in various retinal diseases and would contribute to labor-saving and precision medicine especially in remote areas.

Abstract Background ATP-binding cassette (ABC) transporter proteins constitute a plant gene superfamily crucial for growth, development, and responses to environmental stresses. Despite their identification in various plants like maize, rice, and Arabidopsis, little is known about the information on ABC transporters in pear. To investigate the functions of ABC transporters in pear development and abiotic stress response, we conducted an extensive analysis of ABC gene family in the pear genome. Results In this study, 177 ABC transporter genes were successfully identified in the pear genome, classified into seven subfamilies: 8 ABCAs, 40 ABCBs, 24 ABCCs, 8 ABCDs, 9 ABCEs, 8 ABCFs, and 80 ABCGs. Ten motifs were common among all ABC transporter proteins, while distinct motif structures were observed for each subfamily. Distribution analysis revealed 85 PbrABC transporter genes across 17 chromosomes, driven primarily by WGD and dispersed duplication. Cis-regulatory element analysis of PbrABC promoters indicated associations with phytohormones and stress responses. Tissue-specific expression profiles demonstrated varied expression levels across tissues, suggesting diverse functions in development. Furthermore, several PbrABC genes responded to abiotic stresses, with 82 genes sensitive to salt stress, including 40 upregulated and 23 downregulated genes. Additionally, 91 genes were responsive to drought stress, with 22 upregulated and 36 downregulated genes. These findings highlight the pivotal role of PbrABC genes in abiotic stress responses. Conclusion This study provides evolutionary insights into PbrABC transporter genes, establishing a foundation for future research on their functions in pear. The identified motifs, distribution patterns, and stress-responsive expressions contribute to understanding the regulatory mechanisms of ABC transporters in pear. The observed tissue-specific expression profiles suggest diverse roles in developmental processes. Notably, the significant responses to salt and drought stress emphasize the importance of PbrABC genes in mediating adaptive responses. Overall, our study advances the understanding of PbrABC transporter genes in pear, opening avenues for further investigations in plant molecular biology and stress physiology.

Abstract Background circular RNAs (circRNAs) have been reported to exert important effects in the progression of numerous cancers. However, the functions of circRNAs in intrahepatic cholangiocarcinoma (ICC) are still unclear. Methods circPCNXL2 (has_circ_0016956) were identified in paired ICC by circRNA microarray. Then, we assessed the biological functions of circPCNXL2 by CCK8, EdU, clone formation, transwell, wound healing assays, and xenograft models. RNA pull-down, mass spectrometry, and RNA immunoprecipitation (RIP) were applied to explore the interaction between cirrcPCNXL2 and serine-threonine kinase receptor-associated protein (STRAP). RNA pull-down, RIP and luciferase reporter assays were used to investigate the sponge functions of circPCNXL2. In the end, we explore the effects of circPCNXL2 and trametinib (a MEK1/2 inhibitor) in vivo. Results circPCNXL2 was upregulated in ICC tissues and cell lines, which promoted the proliferation and metastasis of ICC in vitro and in vivo. In terms of the mechanisms, circPCNXL2 could directly bind to STRAP and induce the interaction between STRAP and MEK1/2, resulting in the tumor promotion in ICC by activation of ERK/MAPK pathways. Besides, circPCNXL2 could regulate the expression of SRSF1 by sponging miR-766-3p and subsequently facilitated the growth of ICC. Finally, circPCNXL2 could partially inhibit the anti-tumor activity of trametinib in vivo. Conclusion circPCNXL2 played a crucial role in the progression of ICC by interacting with STRAP to activate the ERK signaling pathway, as well as by modulating the miR-766-3p/SRSF1 axis. These findings suggest that circPCNXL2 may be a promising biomarker and therapeutic target for ICC.

Abstract In vascular networks, the transport across different vessel walls regulates chemical compositions in blood over space and time. Replicating such trans-wall transport with spatial heterogeneity can empower synthetic fluidic systems to program fluid compositions spatiotemporally. However, it remains challenging as existing synthetic channel walls are typically impermeable or composed of homogeneous materials without functional heterogeneity. This work presents a vascular network-inspired fluidic system (VasFluidics), which is functionalizable for spatially different trans-wall transport. Facilitated by embedded three-dimensional (3D) printing, elastic, ultrathin, and semipermeable walls self-assemble electrostatically. Physicochemical reactions between fluids and walls are localized to vary the trans-wall molecules among separate regions, for instance, by confining solutions or locally immobilizing enzymes on the outside of channels. Therefore, fluid compositions can be regulated spatiotemporally, for example, to mimic blood changes during glucose absorption and metabolism. Our VasFluidics expands opportunities to replicate biofluid processing in nature, providing an alternative to traditional fluidics.

Abstract Due to the inevitable presence of quality problems, quality inspection of remote sensing images is indeed an indispensable step between the acquisition and the application of them. However, traditional manual inspection suffers from low efficiency. Hence, we propose a novel deep learning‐based two‐step intelligent system consisting of multiple advanced computer vision models, which first performs image classification by SwinV2 and then accordingly adopts the most appropriate method, such as semantic segmentation by Segformer, to localize the quality problems. Results demonstrate that the proposed method exhibits excellent performance and efficiency, surpassing traditional methods. Furthermore, an initial exploration of applying multimodal models to remote sensing image quality inspection is conducted.

Abstract Background Triosephosphate isomerase 1 (TPI1), as a widely involved glycolytic enzyme, plays a significant role in glucose metabolism and is highly expressed in various tumors. However, its role in lung adenocarcinoma (LUAD) remains incompletely understood. Methods Through bioinformatic analysis, we identified a positive association between high expression of TPI1 and metastasis in LUAD. Western blot, RT‐qPCR, wound healing assays and transwell experiments, were employed to investigate potential mechanisms. Results In this study, bioinformatic analysis showed that high expression of TPI1 was associated with poor prognosis in LUAD patients. We examined the expression of TPI1 in 29 paired LUAD tissues and found that TPI1 expression was higher in LUAD tissues than in paired adjacent noncancerous tissues. Meanwhile, overexpression of TPI1 promoted the epithelial‐mesenchymal transition (EMT) process in LUAD cells, while silencing TPI1 weakened the EMT process. Furthermore, TPI1 was shown to regulate EMT through the MAPK/ERK signaling pathway. Conclusion TPI1 promotes LUAD metastasis by activating the MAPK/ERK signaling pathway.

Heat shock protein 20 (Hsp20) plays a very important role in response to abiotic stressors such as drought; however, in lettuce (Lactuca sativa L.), this gene family is poorly understood. This study used bioinformatics methods to identify 36 members of the lettuce Hsp20 family, which were named LsHsp20–1~LsHsp20–36. Subcellular localization results revealed that 26 members of the LsHsp20 protein family localized to the cytoplasm and nucleus. Additionally, 15 conserved domains were identified in the LsHsp20 protein family, with the number of amino acids ranging from 8 to 50. Gene structure analysis revealed that 15 genes (41.7%) had no introns, and 20 genes (55.5%) had one intron. The proportion of the LsHsp20 secondary structure was random coil > alpha helix > extended strand > beta turn. Chromosome positioning analysis indicated that 36 genes were unevenly distributed on nine chromosomes, and four pairs of genes were collinear. The Ka/Ks ratio of the collinear genes was less than 1, indicating that purifying selection dominated during L. sativa evolution. Thirteen pairs of genes were collinear in lettuce and Arabidopsis, and 14 pairs of genes were collinear in lettuce and tomato. A total of 36 LsHsp20 proteins were divided into 12 subgroups based on phylogenetic analysis. Three types of cis-acting elements, namely, abiotic and biotic stress-responsive, plant hormone-responsive, and plant development-related elements, were identified in the lettuce LsHsp20 family. qRT-PCR was used to analyze the expression levels of 23 LsHsp20 genes that were significantly upregulated on the 7th or 14th day of drought treatment, and the expression levels of two genes (LsHsp20–12 and LsHsp20–26) were significantly increased by 153-fold and 273-fold on the 14th and 7th days of drought treatment, respectively. The results of this study provide comprehensive information for research on the LsHsp20 gene family in lettuce and lay a solid foundation for further elucidation of Hsp20 biological functions, providing valuable information on the regulatory mechanisms of the LsHsp20 family in lettuce drought resistance.

In China, fence net aquaculture practices have been established in some subsidence waters that have been formed in coal mining subsidence areas. Within this dynamic ecological context, diverse fish species grow continuously until being harvested at the culmination of their production cycle. The purpose of this study was to investigate diverse factors influencing the bioavailability and distribution of mercury (Hg) and methylmercury (MeHg), which have high physiological toxicity in fish, in the Guqiao coal mining subsidence area in Huainan, China. Mercury and MeHg were analyzed in 38 fish samples of eight species using direct mercury analysis (DMA-80) and gas chromatography–cold vapor atomic fluorescence spectrometry (GC-CVAFAS). The analysis results show that the ranges of Hg and MeHg content and methylation rate in the fish were 7.84–85.18 ng/g, 0.52–3.52 ng/g, and 0.81–42.68 %, respectively. Meanwhile, conclusions are also summarized as following: (1) Monophagous herbivorous fish that were fed continuously in fence net aquaculture areas had higher MeHg levels and mercury methylation rates than carnivorous fish. Hg and MeHg contents were affected by different feeding habits of fish. (2) Bottom-dwelling fish show higher MeHg levels, and habitat selection in terms of water depth also partially affected the MeHg content of fish. (3) The effect of fence net aquaculture on methylation of fish in subsidence water is mainly from feed and mercury-containing bottom sediments. However, a time-lag is observed in the physiological response of benthic fishes to the release of Hg from sediments. Our findings provides baseline reference data for the ecological impact of fence net aquaculture in waters affected by soil subsidence induced by coal mining in China. Prevalent environmental contaminants within coal mining locales, notably Hg, may infiltrate rain-induced subsidence waters through various pathways.

BackgroundMalignant pleural effusion (MPE) is prevalent among cancer patients, indicating pleural metastasis and predicting poor prognosis. However, accurately identifying MPE in clinical settings is challenging. The aim of this study was to establish an innovative nomogram-derived model based on clinical indicators and serum metal ion levels to identify MPE.MethodsFrom July 2020 to May 2022, 428 patients diagnosed with pleural effusion (PE) were consecutively recruited. Comprehensive demographic details, clinical symptoms, imaging data, pathological information, and laboratory results, including serum metal ion levels, were systematically collected. The nomogram was created by incorporating the most significant predictors identified through LASSO and multivariate logistic regression analysis. The predictors were assigned weighted points based on their respective regression coefficients, allowing for the calculation of a total score that corresponds to the probability of MPE. Internal validation using bootstrapping techniques assessed the nomogram’s performance, including calibration, discrimination, and clinical applicability.ResultsSeven key variables were identified using LASSO regression and multiple regression analysis, including dyspnea, fever, X-ray/CT compatible with malignancy, pleural carcinoembryonic antigen(pCEA), serum neuron-specific enolase(sNSE), serum carcinoembryonic antigen(sCEA), and pleural lactate dehydrogenase(pLDH). Internal validation underscored the superior performance of our model (AUC=0.940). Decision curve analysis (DCA) analysis demonstrated substantial net benefit across a probability threshold range > 1%. Additionally, serum calcium and copper levels were significantly higher, while serum zinc levels were significantly lower in MPE patients compared to benign pleural effusion (BPE) patients.ConclusionThis study effectively developed a user-friendly and reliable MPE identification model incorporating seven markers, aiding in the classification of PE subtypes in clinical settings. Furthermore, our study highlights the clinical value of serum metal ions in distinguishing malignant pleural effusion from BPE. This significant advancement provides essential tools for physicians to accurately diagnose and treat patients with MPE.

IntroductionPorcine deltacoronavirus (PDCoV) is a zoonotic pathogen with a global distribution, capable of infecting both pigs and humans. To mitigate the risk of cross-species transmission and potential outbreaks, it is crucial to characterize novel antiviral genes, particularly those from human hosts.MethodsThis research used HIEC-6 to investigate PDCoV infection. HIEC-6 cells were infected with PDCoV. Samples were collected 48 h postinfection for proteomic analysis.ResultsWe discovered differential expression of MRPS6 gene at 48 h postinfection with PDCoV in HIEC-6 cells. The gene expression initially increased but then decreased. To further explore the role of MRPS6 in PDCoV infection, we conducted experiments involving the overexpression and knockdown of this gene in HIEC-6 and Caco2 cells, respectively. Our findings revealed that overexpression of MRPS6 significantly inhibited PDCoV infection in HIEC-6 cells, while knockdown of MRPS6 in Caco2 cells led to a significant increase of virus titer. Furthermore, we investigated the correlation between PDCoV infection and the expression of MRPS6. Subsequent investigations demonstrated that MRPS6 exerted an augmentative effect on the production of IFN-β through interferon pathway activation, consequently impeding the progression of PDCoV infection in cellular systems. In conclusion, this study utilized proteomic analysis to investigate the differential protein expression in PDCoV-infected HIEC-6 cells, providing evidence for the first time that the MRPS6 gene plays a restrictive role in PDCoV virus infection.DiscussionOur findings initially provide the validation of MRPS6 as an upstream component of IFN-β pathway, in the promotion of IRF3, IRF7, STAT1, STAT2 and IFN-β production of HIEC-6 via dual-activation from interferon pathway.

Hematoma expansion (HE) is an important risk factor for death or poor prognosis in patients with hypertensive intracerebral hemorrhage (HICH). Accurately predicting the risk of HE in patients with HICH is of great clinical significance for timely intervention and improving patient prognosis. Many imaging signs reported in literatures showed the important clinical value for predicting HE. In recent years, the development of radiomics and artificial intelligence has provided new methods for HE prediction with high accuracy. Therefore, this article reviews the latest research progress in CT imaging, radiomics, and artificial intelligence of HE, in order to help identify high-risk patients for HE in clinical practice.

Subject-specific spinal musculoskeletal modeling can help understand the spinal loading mechanism during human locomotion. However, existing literature lacks methods to identify the maximum isometric strength of individual spinal muscles. In this study, a muscle strength identification method combining isokinetic testing and musculoskeletal simulations was proposed, and the influence of muscle synergy and intra-abdominal pressure (IAP) on identified spinal muscle strength was further discussed. A multibody dynamic model of the spinal musculoskeletal system was established and controlled by a feedback controller. Muscle strength parameters were adjusted based on the measured isokinetic moments, and muscle synergy vectors and the IAP piston model were further introduced. The results of five healthy subjects showed that the proposed method successfully identified the subject-specific spinal flexor/extensor strength. Considering the synergistic activations of antagonist muscles improved the correlation between the simulated and measured spinal moments, and the introduction of IAP slightly increased the identified spinal extensor strength. The established method is beneficial for understanding spinal loading distributions for athletes and patients with sarcopenia.

BackgroundPheochromocytoma is one of the most hereditary human tumors with at least 20 susceptible genes undergoing germline and somatic mutations, and other mutations less than 1% -2%. In recent years, other rare mutations have gradually been discovered to be possibly related to the pathogenesis and metastasis of pheochromocytoma. Most patients with pheochromocytoma experience common symptoms like headaches, palpitations, and sweating, while some may have less common symptoms. The diversity of symptoms, genetic mutations, and limited treatment options make management challenging.Case presentationA 53-year-old woman was hospitalized after experiencing episodic epigastric pain for one month. A mass was found in her right adrenal gland and she underwent robot-assisted laparoscopic surgery, revealing a pheochromocytoma. At the 16-month follow-up, multiple metastatic lesions consistent with metastatic pheochromocytoma were found. A germline mutation in the dihydrolipoamide succinyltransferase (DLST) gene (c.330 + 14A>G) was detected, and despite trying chemotherapy and adjuvant therapy, the patient had a limited response with an overall survival of 27 months.ConclusionsDLST mutation is one of the rare pheochromocytoma-related mutated genes, and genetic sequencing is crucial for effective clinical management.

Abstract Rechargeable Li metal batteries have the potential to meet the demands of high‐energy density batteries for electric vehicles and grid‐energy storage system applications. Achieving this goal, however, requires resolving not only safety concerns and a shortened battery cycle life arising from a combination of undesirable lithium dendrite and solid‐electrolyte interphase formations. Here, a series of microcrack‐free anionic network polymer membranes formed by a facile one‐step click reaction are reported, displaying a high cation conductivity of 3.1 × 10−5 S cm−1 at high temperature, a wide electrochemical stability window up to 5 V, a remarkable resistance to dendrite growth, and outstanding non‐flammability. These enhanced properties are attributed to the presence of tethered borate anions in microcrack‐free membranes, which benefits the acceleration of selective Li+ cations transport as well as suppression of dendrite growth. Ultimately, the microcrack‐free anionic network polymer membranes render Li metal batteries a safe and long‐cyclable energy storage device at high temperatures with a capacity retention of 92.7% and an average coulombic efficiency of 99.867% at 450 cycles.

Abstract Background The use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors. Methods Patients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not. Results In univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not. Conclusion In patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

Abstract Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate immune cells is highly related to experimental malaria disease progression, especially the development of murine severe malaria. In the absence of PRL2 in myeloid cells, Plasmodium berghei infection results in augmented lung injury, leading to significantly increased mortality. Intravital imaging revealed greater neutrophilic inflammation and NET formation in the lungs of PRL2 myeloid conditional knockout mice. Depletion of neutrophils prior to the onset of severe disease protected mice from NETs associated lung injury, and eliminated the difference between WT and PRL2 CKO mice. PRL2 regulates neutrophil activation and NET accumulation via the Rac-ROS pathway, thus contributing to NETs associated ALI. Hydroxychloroquine, an inhibitor of PRL2 degradation alleviates NETs associated tissue damage in vivo. Our findings suggest that PRL2 serves as an indicator of progression to severe malaria and ALI. In addition, our study indicated the importance of PRL2 in NET formation and tissue injury. It might open a promising path for adjunctive treatment of NET-associated disease.

In the procedure of carbon peaking and carbon neutrality energy revolution, large-scale renewable energy is aggrandizing frequency regulation capacity of power grid. How to make the best use of new rapid resources, represented by battery energy storage systems (BESS), in the secondary frequency regulation is the key to solve the problem. Firstly, a three-layer frame is designed, embodying area, cluster and plant, which can satisfy the needs for access monitoring and classification decision of various regulation resources in automatic generation control (AGC) system. Secondly, a coordination control strategy including BESS is proposed, and so is the strategy of regulation requirements assignment based on state of charge (SOC) effecting factor in BESS group. Finally, simulations are conducted for continuous disturbance cases from an actual power system, as well as simulations for tripping fault disturbances. The results show that the proposed strategy can improve the SOC consistency between the respective BESS, promoting the availability of BESS, and improve the performance of network frequency response characteristics either.

Convolutional neural networks (CNNs) have been successfully applied to motor imagery (MI)-based brain–computer interface (BCI). Nevertheless, single-scale CNN fail to extract abundant information over a wide spectrum from EEG signals, while typical multi-scale CNNs cannot effectively fuse information from different scales with concatenation-based methods. To overcome these challenges, we propose a new scheme equipped with attention-based dual-scale fusion convolutional neural network (ADFCNN), which jointly extracts and fuses EEG spectral and spatial information at different scales. This scheme also provides novel insight through self-attention for effective information fusion from different scales. Specifically, temporal convolutions with two different kernel sizes identify EEG $\boldsymbol{\mu }$ and $\boldsymbol{\beta }$ rhythms, while spatial convolutions at two different scales generate global and detailed spatial information, respectively, and the self-attention mechanism performs feature fusion based on the internal similarity of the concatenated features extracted by the dual-scale CNN. The proposed scheme achieves the superior performance compared with state-of-the-art methods in subject-specific motor imagery recognition on BCI Competition IV dataset 2a, 2b and OpenBMI dataset, with the cross-session average classification accuracies of 79.39% and significant improvements of 9.14% on BCI-IV2a, 87.81% and 7.66% on BCI-IV2b, 65.26% and 7.2% on OpenBMI dataset, and the within-session average classification accuracies of 86.87% and significant improvements of 10.89% on BCI-IV2a, 87.26% and 8.07% on BCI-IV2b, 84.29% and 5.17% on OpenBMI dataset, respectively. What is more, ablation experiments are conducted to investigate the mechanism and demonstrate the effectiveness of the dual-scale joint temporal-spatial CNN and self-attention modules. Visualization is also used to reveal the learning process and feature distribution of the model.

Abstract Background Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction. Results Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score. Conclusions Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.

Abstract Enveloped viruses encased within a lipid bilayer membrane are highly contagious and can cause many infectious diseases like influenza and COVID-19, thus calling for effective prevention and inactivation strategies. Here, we develop a diatomic iron nanozyme with lipoxidase-like (LOX-like) activity for the inactivation of enveloped virus. The diatomic iron sites can destruct the viral envelope via lipid peroxidation, thus displaying non-specific virucidal property. In contrast, natural LOX exhibits low antiviral performance, manifesting the advantage of nanozyme over the natural enzyme. Theoretical studies suggest that the Fe-O-Fe motif can match well the energy levels of Fe2 minority β-spin d orbitals and pentadiene moiety π* orbitals, and thus significantly lower the activation barrier of cis,cis-1,4-pentadiene moiety in the vesicle membrane. We showcase that the diatomic iron nanozyme can be incorporated into air purifier to disinfect airborne flu virus. The present strategy promises a future application in comprehensive biosecurity control.

Sake may potentially halt the progression of Parkinson's disease due to its properties, yet no studies have explored its effects. This preliminary study aimed to assess the impact of sake supplementation on Parkinson's disease using a zebrafish model. Sixty fish were divided into six groups: control, rotenone (ROT), and groups administered rotenone along with sake at concentrations of 25, 50, 75, and 100 mg/L (25S, 50S, 75S, and 100S). After 28 days of treatment, behavioral responses and the activities of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione-S-transferase (GST), as well as the expressions of TNF-α, IL-1β, and COX-2, were evaluated. The results indicated that rotenone administration significantly reduced crossing number (P = 0.001), entries in the top area (P = 0.001), and time spent in the top area (P = 0.001). It also markedly increased levels of TBARS and SH compared to the control group (P = 0.001). Rotenone significantly decreased CAT, SOD, and GSH activities while increasing GST levels. Furthermore, it upregulated the expressions of TNF-α (P = 0.001), IL-1β (P = 0.001), and COX-2 (P = 0.001). Supplementation with sake, particularly at higher doses, reversed the adverse effects of rotenone on behavioral, oxidative, and inflammatory responses. In conclusion, sake shows promise for preventing Parkinson's disease pending further clinical studies.

The transporter protein ABC subfamily G member 2 (ABCG2) is implicated in epilepsy; however, its specific role remains unclear. In this study, we assessed changes in ABCG2 expression and its role in epilepsy both in vitro and in vivo. We observed an instantaneous increase in ABCG2 expression in epileptic animals and cells. Further, ABCG2 overexpression significantly suppressed the oxidative stress and apoptosis induced by glutamate, kainic acid (KA), and lipopolysaccharide (LPS) in neuronal and microglia cells. Furthermore, inhibiting ABCG2 activity offset this protective effect. ABCG2-deficient mice (ABCG2−/−) showed shorter survival times and decreased survival rates when administered with pentylenetetrazole (PTZ). We also noticed the accumulation of signal transducer and activator of transcription 1 (STAT1) and decreased phosphorylation of mammalian target of rapamycin kinase (mTOR) along with increased ISGylation in ABCG2−/− mice. ABCG2 overexpression directly interacted with STAT1 and mTOR, leading to a decrease in their ISGylation. Our findings indicate the rapid increase in ABCG2 expression acts as a shield in epileptogenesis, indicating ABCG2 may serve as a potential therapeutic target for epilepsy treatment.

Numerous studies have explored the effects of background music on reading comprehension, however, little is known about how native language (L1) lyrics and second language (L2) lyrics in background music influence reading comprehension performance for college students. The present study used a mixed experimental design to examine the effects of listening habits (between-participants variable: non-listeners or listeners), music type (between-participants variable: L1 (Mandarin) pop music, L2 (English) pop music or no music) and text language (within-participants variable: L1 or L2) on reading comprehension of college students in East China. A total of 90 participants (50 females) were screened into non- listeners (n = 45) and listeners (n = 45), and then were randomly assigned to one of three groups: Mandarin pop music group (n = 30), English pop music group (n = 30) and no music group (n = 30). The results showed that reading comprehension performance was negatively affected by music with lyrics compared to the no music condition. Furthermore, Chinese/English reading comprehension was reduced more by pop music in the same language as the written texts. As expected, non-listeners were more negatively affected by music with lyrics than listeners. For both listeners and non-listeners, average reading comprehension accuracy rates were the lowest in the condition of music with native language lyrics. Overall, our research findings indicate that listening to pop music with lyrics reduces reading comprehension performance. However, listening to background music cause much less distraction if the students commonly listen to music while reading. The current study supports the duplex-mechanism account of auditory distraction.

In trauma first aid, rapid hemostasis is a priority, extricating patients from hemorrhagic shock and infection risks. This paper explores novel hemostatic materials, using ion-crosslinking and freeze-drying techniques. Iterative experiments determined optimal conditions for the temperature-variable mixing-freeze-drying chemical reaction of sodium alginate (SA)/silk fibroin (SF). We used SA, SA/SF, SA/SF-TB and commercial hemostatic sponge control samples to perform hemostasis experiments on rat liver injury and femoral artery injury models, and to perform wound healing experiments on rat back full-layer skin. The results showed that the hemostatic time and blood loss of SA/SF-TB group rats (liver hemorrhage model: 397.17 ± 34.80 mg, 77.83 ± 7.41 s; Femoral artery bleeding model: 940.33 ± 41.93 mg, 96.83 ± 4.07 s) was significantly better than other experimental groups, and similar to the commercial group. The wound healing experiment showed that the new granulation tissue thickness of SA/SF-TB group was thicker (380.39 ± 28.56 μm) at day 14. In addition, the material properties and biocompatibility of sponges were characterized by cell experiments and in vivo embedding experiments. All the results showed that the SA/SF-TB hemostatic sponge prepared in this study could not only seal the wound quickly and stop bleeding, but also promote the growth of epidermal cells and fibroblasts and accelerate wound healing. This new material solves the shortcomings of traditional materials such as low stability, limited shelf life, high unit price, and has good biocompatibility, easy preparation, rapid hemostasis and other excellent properties. Therefore, this innovative hemostatic material has great prospects and potential in clinical applications.

Abstract Thermoelectric devices (TEDs) show great potential for waste heat energy recycling and sensing. However, existing TEDs cannot be self‐adapted to the complex quadratic surface, leading to significant heat loss and restricting their working scenario. Here, surface‐conformable origami‐TEDs (o‐TEGs) are developed through programmable crease‐designed origami substrates and the screen‐printing TE legs. Compared with “π” structured TEDs, the origami design (with heat conductive materials) changed the heat‐transferring direction of the laminated TE legs, resulting in an enhancement in enlarging ΔT/THot and Vout by 5.02 and 3.51 times. Four o‐TEDs with different creases designs are fabricated to verify the heat recycling ability on plane and central quadratic surfaces. Demonstrating a high Vout density (up to 0.98 −2at ΔT of 50 K) and good surface conformability, o‐TEDs are further used in thermal touch panels attached to multiple surfaces, allowing information to be wirelessly transferred on a remote display via finger‐writing.

Transferrin (Tf), widely known for its role as an iron-binding protein, exemplifies multitasking in biological processes. The role of Tf in iron metabolism involves both the uptake of iron from Tf by various cells, as well as the endocytosis mediated by the complex of Tf and the transferrin receptor (TfR). The direct conjugation of the therapeutic compound and immunotoxin studies using Tf peptide or anti-Tf receptor antibodies as targeting moieties aims to prolong drug circulation time and augment efficient cellular drug uptake, diminish systemic toxicity, traverse the blood-brain barrier, restrict systemic exposure, overcome multidrug resistance, and enhance therapeutic efficacy with disease specificity. This review primarily discusses the various biological actions of Tf, as well as the development of Tf-targeted nano-based drug delivery systems. The goal is to establish the use of Tf as a disease-targeting component, accentuating the potential therapeutic applications of this protein.

Minimally invasive thoracic surgery, including video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery, has been proven to have an advantage over open thoracotomy with less pain, fewer postoperative complications, faster discharge, and better tolerance among elderly patients. We introduce a uniportal robot-assisted thoracoscopic double-sleeve lobectomy performed on a patient following neoadjuvant immunotherapy. Specialized instruments like customized trocars with a reduced diameter, bulldog clamps, and double-needle sutures were utilized to facilitate the maneuverability through the single incision. This technique integrates the merits of multiport robot-assisted thoracic surgery with uniportal video-assisted thoracoscopic surgery.

BackgroundAcute lung injury (ALI)/severe acute respiratory distress syndrome (ARDS) is a serious clinical syndrome characterized by a high mortality rate. The pathophysiological mechanisms underlying ALI/ARDS remain incompletely understood. Considering the crucial role of immune infiltration and macrophage polarization in the pathogenesis of ALI/ARDS, this study aims to identify key genes associated with both ALI/ARDS and M1 macrophage polarization, employing a combination of bioinformatics and experimental approaches. The findings could potentially reveal novel biomarkers for the diagnosis and management of ALI/ARDS.MethodsGene expression profiles relevant to ALI were retrieved from the GEO database to identify co-upregulated differentially expressed genes (DEGs). GO and KEGG analyses facilitated functional annotation and pathway elucidation. PPI networks were constructed to identify hub genes, and differences in immune cell infiltration were subsequently examined. The expression of hub genes in M1 versus M2 macrophages was evaluated using macrophage polarization datasets. The diagnostic utility of CD274 (PD-L1) for ARDS was assessed by receiver operating characteristic (ROC) analysis in a validation dataset. Experimental confirmation was conducted using two LPS-induced M1 macrophage models and an ALI mouse model. The role of CD274 (PD-L1) in M1 macrophage polarization and associated proinflammatory cytokine production was further investigated by siRNA-mediated silencing.ResultsA total of 99 co-upregulated DEGs were identified in two ALI-linked datasets. Enrichment analysis revealed that these DEGs were mainly involved in immune-inflammatory pathways. The following top 10 hub genes were identified from the PPI network: IL-6, IL-1β, CXCL10, CD274, CCL2, TLR2, CXCL1, CCL3, IFIT1, and IFIT3. Immune infiltration analysis revealed a significantly increased abundance of M1 and M2 macrophages in lung tissue from the ALI group compared to the control group. Subsequent analysis confirmed that CD274 (PD-L1), a key immunological checkpoint molecule, was highly expressed within M1 macrophages. ROC analysis validated CD274 (PD-L1) as a promising biomarker for the diagnosis of ARDS. Both in vitro and in vivo experiments supported the bioinformatics analysis and confirmed that the JAK-STAT3 pathway promotes CD274 (PD-L1) expression on M1 macrophages. Importantly, knockdown of CD274 (PD-L1) expression potentiated M1 macrophage polarization and enhanced proinflammatory cytokines production.ConclusionThis study demonstrates a significant correlation between CD274 (PD-L1) and M1 macrophages in ALI/ARDS. CD274 (PD-L1) functions as a negative regulator of M1 polarization and the secretion of proinflammatory cytokines in macrophages. These findings suggest potential new targets for the diagnosis and treatment of ALI/ARDS.

ABSTRACTThe accessory protein ORF6 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key interferon (IFN) antagonist that strongly suppresses the production of primary IFN as well as the expression of IFN-stimulated genes. However, how host cells respond to ORF6 remains largely unknown. Our research of ORF6-binding proteins by pulldown revealed that E3 ligase components such as Cullin 4B (CUL4B), DDB1, and RBX1 are potential ORF6-interacting proteins. Further study found that the substrate recognition receptor PRPF19 interacts with CUL4B, DDB1, and RBX1 to form a CRL4B-based E3 ligase, which catalyzes ORF6 ubiquitination and subsequent degradation. Overexpression of PRPF19 promotes ORF6 degradation, releasing ORF6-mediated IFN inhibition, which inhibits SARS-CoV-2 replication. Moreover, we found that activation of CUL4B by the neddylation inducer etoposide alleviates lung lesions in a SARS-CoV-2 mouse infection model. Therefore, targeting ORF6 for degradation may be an effective therapeutic strategy against SARS-CoV-2 infection.IMPORTANCEThe cellular biological function of the ubiquitin-proteasome pathway as an important modulator for the regulation of many fundamental cellular processes has been greatly appreciated. The critical role of the ubiquitin-proteasome pathway in viral pathogenesis has become increasingly apparent. It is a powerful tool that host cells use to defend against viral infection. Some cellular proteins can function as restriction factors to limit viral infection by ubiquitin-dependent degradation. In this research, we identificated of CUL4B-DDB1-PRPF19 E3 Ubiquitin Ligase Complex can mediate proteasomal degradation of ORF6, leading to inhibition of viral replication. Moreover, the CUL4B activator etoposide alleviates disease development in a mouse infection model, suggesting that this agent or its derivatives may be used to treat infections caused by SARS-CoV-2. We believe that these results will be extremely useful for the scientific and clinic communities in their search for cues and preventive measures to combat the COVID-19 pandemic.

IntroductionIn 2021, the World Health Organization published a new classification system for central nervous system tumors. This study reclassified the adult diffuse glioma (ADG) into astrocytoma, oligodendroglioma, and glioblastoma (GBM) according to the new tumor classification.MethodsThe association of TERT promoter (pTERT) mutation, MGMT methylation, and CD47/TIGIT expression with patient prognosis was investigated.ResultsImmunohistochemical analysis showed that the expression levels of CD47 and TIGIT in tumor tissues were significantly higher than those in normal brain tissues. CD47 levels were higher in GBM and grade 4 astrocytoma tissues. TIGIT expression was also higher in patients with GBM. The high expressions of CD47, TIGIT, and CD47/TIGIT were positively correlated with MGMT unmethylation but not pTERT mutation. Moreover, MGMT unmethylation was associated with poor overall survival in astrocytoma. High CD47, TIGIT, and CD47/TIGIT levels were associated with significantly reduced survival in ADG and GBM. GBM, MGMT unmethylation, and high CD47 expression were independent prognostic factors for overall survival in ADG.DiscussionCollectively, these results showed that the MGMT unmethylation and high levels of CD47 and TIGIT are associated with a poor prognosis in ADG. Patients with high CD47 and TIGIT expression may benefit from anti-CD47 and TIGIT immunotherapy.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidin-related antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota.

BackgroundExisting studies on the relationship between tea intake and lung diseases have yielded inconsistent results, leading to an ongoing dispute on this issue. The impact of tea consumption on the respiratory system remained elucidating.Materials and methodsWe conducted a two-sample Mendelian randomization (MR) study to evaluate the associations between five distinct tea intake phenotypes and 15 different respiratory outcomes using open Genome-wide association study (GWAS) data. The inverse variance weighted (IVW) was used for preliminary screening and a variety of complementary methods were used as sensitivity analysis to validate the robustness of MR estimates. Pathway enrichment analysis was used to explore possible mechanisms.ResultsIVW found evidence for a causal effect of standard tea intake on an increased risk of lung squamous cell cancer (LSCC) (OR = 1.004; 95% CI = 1.001–1.007; P = 0.00299). No heterogeneity or pleiotropy was detected. After adjustment for potential mediators, including smoking, educational attainment, and time spent watching television, the association was still robust in multivariable MR. KEGG and GO enrichment predicted proliferation and activation of B lymphocytes may play a role in this causal relation. No causalities were observed when evaluating the effect of other kinds of tea intake on various pulmonary diseases.ConclusionOur MR estimates provide causal evidence of the independent effect of standard tea intake (black tea intake) on LSCC, which may be mediated by B lymphocytes. The results implied that the population preferring black tea intake should be wary of a higher risk of LSCC.

Jieyu Anshen Granules (JY) is a traditional Chinese medicine formula commonly used as an adjuvant treatment for Alzheimer's disease (AD) complicated with depression. However, the specific underlying mechanisms and therapeutic targets of JY remain unclear. We used the TCMSP, TCMID, BATMAN-TCM, and other databases to screen the components and assumed targets of JY. Next, the GEO and DisGeNET databases were used to identify the related targets of both AD and Major Depressive Disorder (MDD). Enrichment analyses of core targets were performed, and the main components and core targets of JY for the comorbidity of AD and MDD were identified via protein–protein interaction (PPI) network construction and machine learning algorithms. Lastly, we verified binding affinity using the AutoDock software and molecular docking was performed. A total of 171 components were identified from JY, and 979 targets were obtained from the screening process. Bioinformatics analysis displayed 397 differentially expressed genes (DEGs) were shared by AD and MDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis revealed significant enrichment of genes associated with neurotransmitter receptor activity, G protein-coupled amine receptor activity, as well as signaling pathways such as the cAMP signaling pathway, PI3K-Akt signaling pathway, and cholinergic synapses. Through the PPI network and machine learning, we identified three hub genes (Ataxia telangiectasia-mutated gene [ATM], Colony stimulating factor 1 receptor [CSF1R], EPH receptor B2 [EPHB2]) as potential therapeutic targets. Molecular docking confirmed that the components of JY (Mairin, Hederagenin, 3-Epioleanolic Acid) could effectively bind to multiple key targets. This study revealed the effective components and potential mechanisms associated with JY treatment regarding AD and MDD comorbidities, offering valuable insights into promising therapeutic targets for subsequent studies.

The Pan-Third Pole region comprises multiple nations affected by climate vulnerability and energy inequality, wherein promoting energy transitions in rural households would provide a path to combat climate change. Identifying the factors that drive rural household energy consumption and the transition is important. This study performed a micro-survey of 1060 rural households in five countries in the Pan-Third Pole region and empirically analyzed the relationships between off-farm income, energy consumption, and energy transitions. The off-farm income of rural households was found to have a significantly positive effect (p

Abstract The rapid expansion of large-scale pig farming has brought about a surge in viral diseases with high morbidity rates and diverse manifestations. This widespread occurrence of multiple viral diseases in pig farms has inflicted severe economic losses on the global swine industry. Consequently, there is an urgent need for eco-friendly and efficient antiviral drugs that can effectively combat viruses and prevent diseases such as PEDV, PRRSV, PRV, and other viral infections. To this end, we conducted a study on the antiviral activity and cytotoxicity of eleven different Chinese herbal extracts (CHE) against PRV. In vitro testing of several extracts, namely, Echinacea, Ilex purpurea Hassk, Ganoderma lucidum Kars, Taraxacum mongolicum, and Ilex rotunda Thunb, exhibited remarkable inhibition of PRV infection without causing any cytotoxic effects. Specifically, their antiviral selectivity indexes were significantly higher, with values ranging from 6- to 144-fold. The antiviral efficacy of five CHEs was evaluated against other RNA viruses, including PRRSV and PEDV. The extracts showed substantial inhibition of PEDV and PRRSV proliferation. Echinacea and Ilex purpurea Hassk extracts exhibited the highest virus inhibitory effects. To understand the antiviral mechanisms underlying their potent activity, a time-of-addition experiment was conducted. The results indicated that these extracts effectively targeted the early infection and postinfection stages of PRV, PEDV, and PRRSV. The study found that the Chinese herbal extracts, Echinacea and Ilex purpurea Hassk, had both direct and indirect effects on virus particles and cellular targets, demonstrating broad-spectrum antiviral activity against multiple clinical strains of PRV and PEDV. These findings provide a strong foundation for the development of herbal medicines to prevent and treat infections caused by PRV, PEDV and PRRSV in the swine industry. The identified extracts show great promise for the formulation of effective and environmentally friendly antiviral interventions. Graphical Abstract

Abstract Malaria remains one of the deadliest infectious diseases. Transcriptional regulation effects of noncoding variants in this unusual genome of malaria parasites remain elusive. We developed a sequence-based, ab initio deep learning framework, MalariaSED, for predicting chromatin profiles in malaria parasites. The MalariaSED performance was validated by published ChIP-qPCR and TF motifs results. Applying MalariaSED to ~ 1.3 million variants shows that geographically differentiated noncoding variants are associated with parasite invasion and drug resistance. Further analysis reveals chromatin accessibility changes at Plasmodium falciparum rings are partly associated with artemisinin resistance. MalariaSED illuminates the potential functional roles of noncoding variants in malaria parasites.

Abstract The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs.

Abstract Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway in neoplasia.

Abstract To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P