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Eastern equine encephalitis virus (EEEV) is the most virulent alphavirus that infects humans, and many survivors develop neurological sequelae, including paralysis and intellectual disability. Alphavirus spike proteins comprise trimers of heterodimers of glycoproteins E2 and E1 that mediate binding to cellular receptors and fusion of virus and host cell membranes during entry. We recently identified very-low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as cellular receptors for EEEV and a distantly related alphavirus, Semliki Forest virus (SFV). Here, we use single-particle cryo-electron microscopy (cryo-EM) to determine structures of the EEEV and SFV spike glycoproteins bound to the VLDLR ligand-binding domain and found that EEEV and SFV interact with the same cellular receptor through divergent binding modes. Our studies suggest that the ability of LDLR-related proteins to interact with viral spike proteins through very small footprints with flexible binding modes results in a low evolutionary barrier to the acquisition of LDLR-related proteins as cellular receptors for diverse sets of viruses., (© 2024. The Author(s).)

Objective: This study aimed to isolate and analyze the components in cedar pine needles (needle leaves of Cedrus deodara (Roxb.) G. Don) that exhibit anti-obesity effects, as determined through animal experiments., Methods: The extract of cedar pine needles was separated into four fractions of different polarities using a macroporous resin column. The fraction that retained anti-obesity activity was evaluated based on the results of animal experiments. Monomeric compounds were structurally characterized and isolated from the active fraction using a preparative liquid chromatography system. Combined with subsequent glucose gel chromatographic separation. The content of the separated components was determined using ultrahigh performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS)., Results: The water-washed fraction retained anti-obesity activity of the cedar pine needles more effectively. A total of 16 compounds were separated from this fraction, and the contents of 14 of these compounds were determined to be present in cedar pine needles., Conclusion: Nine components, namely p-hydroxy benzyl alcohol, chlorogenic acid, vanillic acid, syringic acid, P-coumaric acid, sinapic acid, benzoic acid, phenylacetic acid, salicylic acid, were characterized and determined for the first time in cedar pine needles. The components with anti-obesity activity in the pine needles of Cedrus are mainly derived from phenolic acids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Liu, Guo, Zhang, Li, Peng, Ma and Shi.)

Western equine encephalitis virus (WEEV) is an arthropod-borne virus (arbovirus) that frequently caused major outbreaks of encephalitis in humans and horses in the early twentieth century, but the frequency of outbreaks has since decreased markedly, and strains of this alphavirus isolated in the past two decades are less virulent in mammals than strains isolated in the 1930s and 1940s 1-3 . The basis for this phenotypic change in WEEV strains and coincident decrease in epizootic activity (known as viral submergence 3 ) is unclear, as is the possibility of re-emergence of highly virulent strains. Here we identify protocadherin 10 (PCDH10) as a cellular receptor for WEEV. We show that multiple highly virulent ancestral WEEV strains isolated in the 1930s and 1940s, in addition to binding human PCDH10, could also bind very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), which are recognized by another encephalitic alphavirus as receptors 4 . However, whereas most of the WEEV strains that we examined bind to PCDH10, a contemporary strain has lost the ability to recognize mammalian PCDH10 while retaining the ability to bind avian receptors, suggesting WEEV adaptation to a main reservoir host during enzootic circulation. PCDH10 supports WEEV E2-E1 glycoprotein-mediated infection of primary mouse cortical neurons, and administration of a soluble form of PCDH10 protects mice from lethal WEEV challenge. Our results have implications for the development of medical countermeasures and for risk assessment for re-emerging WEEV strains., (© 2024. The Author(s).)

Pro-inflammatory M1 macrophages possess the ability to change the immunosuppressive tumor microenvironment by releasing various inflammatory factors simultaneously, which can effectively inhibit tumor progression and relapse. Promoting macrophage polarization towards M1 may be an effective way to treat Melanoma. However, the risk of cytokine storm caused by the proliferation and excessive activation of M1 macrophages greatly limits it as a biosafety therapeutic strategy in anti-tumor immunotherapy. Therefore, how to engineer natural M1 macrophage to a biocompatible biomaterial that maintains the duration time of tumor suppressive property duration time still remains a huge challenge. To achieve this goal, we developed an injectable macroporous hydrogel (M1LMHA) using natural M1 macrophage lysates and alginate as raw materials. M1LMHA had excellent biocompatibility, adjustable degradation rate and could sustainably release varieties of natural inflammatory factors, such as tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), etc. M1LMHA could repolarize anti-inflammatory M2 macrophages to M1 macrophages by the synergistic effect of released tiny inflammatory factors via the NF-κB pathway. This study supported that M1LMHA might be an effective and safe tool to activate tumor-associated immune cells, improving the efficiency of anti-tumor immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prognosis for patients with colorectal cancer (CRC) remains worse than expected due to metastasis, recurrence, and resistance to chemotherapy. Colorectal cancer stem cells (CRCSCs) play a vital role in tumor metastasis, recurrence, and chemotherapy resistance. However, there are currently no prognostic markers based on CRCSCs-related genes available for clinical use. In this study, single-cell transcriptome sequencing was employed to distinguish cancer stem cells (CSCs) in the CRC microenvironment and analyze their properties at the single-cell level. Subsequently, data from TCGA and GEO databases were utilized to develop a prognostic risk model for CRCSCs-related genes and validate its diagnostic performance. Additionally, functional enrichment, immune response, and chemotherapeutic drug sensitivity of the relevant genes in the risk model were investigated. Lastly, the key gene RPS17 in the risk model was identified as a potential prognostic marker and therapeutic target for further comprehensive studies. Our findings provide new insights into the prognostic treatment of CRC and offer novel perspectives for a systematic and comprehensive understanding of CRC development., (© 2024. The Author(s).)

Background: Knee osteoarthritis (KOA) is reputedly the most common musculoskeletal disease of the lower limbs and the main cause of pain and disability among older individuals. Pain is the most significant and widespread symptom of KOA. The descending pain inhibitory system has a cardinal role in normal pain consciousness, and its malfunction may be one of the pathophysiological mechanisms in KOA. Crucially, the rostral ventromedial medulla (RVM) and periaqueductal gray (PAG), as important components of the descending pain inhibitory system, directly modulate the activity of the spinal neurons involved in pain transmission. Tuina, a manual therapy, is effective and safe for reducing clinical symptoms of KOA; however, the mechanism that influences pain through the descending pain inhibitory system in KOA is unclear., Objective: This study aims to investigate the modulatory implications of Tuina on the RVM and PAG, which have critical roles in the descending pain inhibitory system in patients with KOA., Methods: This randomized controlled parallel trial will be conducted at the Tuina Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine (Zhengzhou, China). Patients with KOA will be randomly assigned (1:1) to 6 weeks of health education or Tuina. All patients in both groups will accept a resting-state functional magnetic resonance scan at the beginning and end of the experiment, and the resting-state functional connectivity and the voxel-based morphometry analysis will be performed to detect the RVM and PAG function and structure changes. The clinical outcome assessments will be (1) the pressure pain thresholds, (2) the Numerical Rating Scale, (3) the Hamilton Depression Scale (HAMD), and (4) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Considering that this trial is a study of resting-state functional magnetic resonance imaging technology, resting-state functional connectivity and voxel-based morphometry are the primary outcomes, and clinical outcome assessments are secondary outcomes. Adverse events will be documented and assessed throughout. All main analyses will be carried out on the basis of the intention-to-treat principle. The outcome evaluators and data statisticians will be masked to the treatment group assignment to reduce the risk of bias., Results: This trial was approved by the ethics committee of the Third Affiliated Hospital of Henan University of Chinese Medicine. Enrollment began in December 2023, and the results of this trial are expected to be submitted for publication in May 2025., Conclusions: This trial will identify a possible relationship between function and structure changes of RVM and PAG and the improvement of clinical variables, elucidating the effect of Tuina on the descending pain inhibitory system of patients with KOA. This trial will provide much-needed knowledge for Tuina for patients with KOA., Trial Registration: Chinese Clinical Trial Registry ChiCTR2300070289; https://www.chictr.org.cn/showproj.html?proj=182570., International Registered Report Identifier (irrid): PRR1-10.2196/52820., (©Hui Xu, Zheng Wang, Zhen Wang, Hang Zhou, Juan Guo, Wanyu Li, Yunfeng Zhou. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.02.2024.)

Background: Coronavirus disease (COVID)-19 can lead to chronic lung damage and respiratory issues, potentially increasing surgical difficulty and risk for patients with non-small-cell lung cancer (NSCLC). However, the impacts of a COVID-19 history on early outcomes in NSCLC patients remain controversial., Objectives: To evaluate the effect of COVID-19 history on early outcomes in NSCLC patients and identify high-risk groups undergoing radical resection based on the largest Chinese multi-center real-world data to date., Design: Multi-center retrospective cohort study., Methods: NSCLC patients with (POCVD group) or without (NCVD group) a history of COVID-19 who underwent radical surgery at six institutions from January 2022 to January 2024 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM) was utilized to minimize patient selection bias., Results: Out of 7932 cases included, PSM resulted in 3021 cases per group. The two groups were comparable regarding the proportion of male patients (52.0% vs 51.6%) and those aged ⩾70 years (13.3% vs 13.8%). Although the two groups had comparable incidences of complications with Clavien-Dindo grades ⩾II (13.0% vs 14.4%, p  = 0.117), the POCVD group had longer surgical durations (120.87 ± 40.23 min vs 110.74 ± 38.76 min, mean difference (95% confidence interval (CI) = 10.13 (8.138-12.122)) and higher rates of respiratory complications than the NCVD group. Subgroup logistic regression analysis indicated that patients aged ⩾70 years (odds ratio (OR) (95% CI) = 1.322 (1.022-1.876)) and those with a smoking history (OR (95% CI) = 1.235 (1.008-1.543)) had an increased risk of developing complications with Clavien-Dindo grades ⩾II. Further analysis confirmed that these high-risk patients experienced extended surgical durations, longer chest tube drainage, and prolonged postoperative hospital stay, along with increased postoperative respiratory complications following COVID-19., Conclusion: Generally, radical resection is safe for NSCLC patients with a COVID-19 history. However, these patients experienced prolonged surgical durations and a higher incidence of postoperative respiratory complications compared to those without a COVID-19 history. In addition, individuals aged ⩾70 years or with a smoking history faced elevated surgical risks following COVID-19.

High concentrations of arsenic in soil and plant systems are a threat to human health and ecosystems. The levels of phosphate ions in the soil strongly influence the soil efficacy and arsenic absorption by plants. This study investigated the effects of phosphate-solubilizing fungi (PSF) on environmental factors and structural changes in microbial community in soils contaminated with arsenic. Four experimental groups were created: control (CK), Penicillium GYAHH-CCT186 (W 186 ), Aspergillus AHBB-CT196 (W 196 ), and Penicillium GYAHH-CCT186 + Aspergillus AHBB-CT196 (W 186  + W 196 ), with Pakchoi (Brassica chinensis L.) as the test plant. Analysis of altered nutrient levels, enzyme activities and microbial community structure in the soil as well as the growth and physiological characteristics of Pakchoi, revealed a significant increase in the available phosphorus (AP), organic matter (OM), cation exchange capacity (CEC) and available arsenic (AAs) content of the soil following W 186  + W 196 , W 196 and W 186 treatments. All experimental treatments enhanced the activity of soil β-glucosidase (β-GC) and soil catalase (S-CAT). W 186  + W 196 and W 196 treatments significantly enhanced soil acid phosphatase (S-ACP) activity. Besides, W 186  + W 196 treatment significantly induced dehydrogenase (S-DHA) activity. Further, of the treatment with PSF increased the fresh weight, root length, plant height and chlorophyll levels while decreasing the arsenic accumulation in Pakchoi. Exposure to PSF also increased the activity of Ascomycota, Basidiomycota, Chytridiomycota, unclassified_Fungi, Mortierellomycota, Cryptomycota and Rozellomycota in the soil. The relative abundance of Ascomycota, Basidiomycota, and Mortierellomycota was positively correlated with the available nutrients (except iron) in the soil as well as enzyme activities. Consequently, the PSF improved the quality of soil and the safety of Pakchoi, suggesting that PSF can be utilized for the remediation of arsenic-contaminated soil., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Tuina is an effective complementary and alternative therapy. However, no bibliometric analysis has explored the global research status and emerging trends of tuina. Therefore, our study aimed to provide a perspective on the current state and frontier trends in the field., Design: Bibliometric analysis SETTING: Tuina-related publications between January 1, 2003, and December 31, 2022, were obtained from the Web of Science Core Collection database., Main Outcome Measures: The knowledge graph software CiteSpace and VOSViewer were used to quantitatively analyse annual trends in annual publication volume, journals, countries, institutions, authors, cited references, and keywords., Results: Overall, 1877 articles were obtained. Consequently, the number of annual publications in tuina gradually increased. China published the most articles (1402 articles, 58.01%), followed by the Chinese Academy of Sciences (110 articles, 2.57%). Original and review articles were the two main types of publications. Photonics Research ranked first (101 articles, 5.38%) as the most influential affiliate and productive journal. These articles come from 8423 authors, among whom Min Fang published the most publications, and Ernst E was co-cited most often. According to the keyword co-occurrence analysis, the new research frontiers were meta-analyses., Conclusion: This comprehensive bibliometric study analysed the publications on tuina and presented them visually, revealing new research trends, pivotal points, research hotspots, and frontiers. Prospective strategies and potential directions for further studies were also provided., Competing Interests: Declaration of Competing Interest The author declares no conflict of interest in this work., (Copyright © 2023. Published by Elsevier Ltd.)

Enzyme allocation (or synthesis) is a crucial microbial trait that mediates soil biogeochemical cycles and their responses to climate change. However, few microbial ecological models address this trait, particularly concerning multiple enzyme functional groups that regulate complex biogeochemical processes. Here, we aim to fill this gap by developing a COmpetitive Dynamic Enzyme ALlocation (CODEAL) scheme for six enzyme groups that act as indicators of inorganic nitrogen (N) transformations in the Microbial-ENzyme Decomposition (MEND) model. This allocation scheme employs time-variant allocation coefficients for each enzyme group, fostering mutual competition among the multiple groups. We show that the principle of enzyme cost minimization is achieved by using the substrate's saturation level as the factor for enzyme allocation, resulting in an enzyme-efficient pathway with minimal enzyme cost per unit metabolic flux. It suggests that the relative substrate availability affects the trade-off between enzyme production and metabolic flux. Our research has the potential to give insights into the nuanced dynamics of the N cycle and inspire the evolving landscape of enzyme-mediated biogeochemical processes in microbial ecological modeling, which is gaining increasing attention., (© 2023. The Author(s).)

The Xikuangshan (XKS) mine was selected for a comprehensive Sb-related hydrogeochemical study because of its significant Sb contamination in water systems. Hydrochemical data, specifically multi-isotope (H, O, S, and Sr) data, were conducted to elucidate the primary sources and migration processes of Sb responsible for water system contamination. At the XKS Sb mine, water is near-neutral to alkaline and is characterized by high concentrations of SO 4 2- and Sb. Sb occurs as Sb(OH) 6 - (the dominant species) in these oxidized waters. The hydrochemistry is mainly controlled by carbonate dissolution and silicate weathering. δ 2 H H2O and δ 18 O H2O values indicate that the infiltration recharge of mine water and mining activities regulate the migration of Sb in groundwater. δ 34 S SO4 and δ 18 O SO4 values indicate that dissolved SO 4 2- and Sb primarily come from stibnite oxidation, bacterial SO 4 2- reduction has either not occurred or is extremely weak, and the reductive dissolution of Fe (III) hydroxides does not significantly affect Sb migration in water. The 87 Sr/ 86 Sr ratios further indicate that the discharge of solid mine wastes leaching and smelting water is a crucial source of Sb contamination in groundwater. In addition, the relationship between δ 34 S SO4 and δ 87 Sr values suggests the complexity of the contamination source and migration of Sb in water. Finally, a robust conceptual hydrogeochemical model was developed using isotopic tools in combination with detailed hydrogeological and hydrochemistry characterization to describe the contamination source and migration of Sb in water systems at the XKS Sb mine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this work, a dual interfacial passivation layer (IPL) consisting of TaON/GeON is implemented in GaAs metal-oxide-semiconductor (MOS) capacitors with ZrTaON as a high-k layer to obtain superior interfacial and electrical properties. As compared to the samples with only GeON IPL or no IPL, the sample with the dual IPL of TaON/GeON exhibits the best performance: low interface-state density (1.31 × 10 12 cm -2 eV -1 ), small gate leakage current density (1.62 × 10 -5 A cm -2 at V fb + 1 V) and large equivalent dielectric constant (18.0). These exceptional results can be attributed to the effective blocking action of the TaON/GeON dual IPL. It efficiently prevents the out-diffusion of Ga/As atoms and the in-diffusion of oxygen, thereby safeguarding the gate stack against degradation. Additionally, the insertion of the thin TaON layer successfully hinders the interdiffusion of Zr/Ge atoms, thus averting any reaction between Zr and Ge. Consequently, the occurrence of defects in the gate stack and at/near the GaAs surface is significantly reduced.

Purpose: Tuina is a nonpharmacological modality for pain relief that has found applications in the treatment of several pain disorders. Tuina analgesia has been increasingly studied; however, few studies have focused on the previous publication trends, prevalent research areas, collaborations, and other factors. This study aimed to systematically analyze research trends and hot topics in the field of tuina analgesia over the past 30 years, using bibliometric analysis, to inform future research., Methods: The web of science database was searched for literature on tuina analgesia from 1992-2023. VOSviewer and CiteSpace were used to analyze annual publication volumes, countries, institutions, journals and CO-cited journals, authorship, articles, and keywords and their relevance, and to perform co-occurrence and clustering analyses., Results: A total of 621 literature elements were included in the analysis. The annual volume of publications has increased steadily in recent years. The top three high-yielding countries were the United States, China, and Canada, respectively. The top three institutional outputs were from Shanghai University of Chinese medicine, Beijing University of Chinese medicine, and McMaster University, respectively. Notably, there was an imbalance between national outputs and centrality, with higher centrality in the United States (0.35) and lower in China (0.01). Cochrane Database of Systematic Reviews was the journal with the most publications (22), and PAIN was the most influential co-cited journals (publications=306). Moreover, current research in this field was dominated by studies on Tuina for relieving postoperative pain, the effectiveness of Tuina analgesia, and Tuina treatment for pain accompanied by anxiety., Conclusion: This study employed bibliometrics to analyze the literature on Tuina for pain treatment over a 30-year period, identifying potential collaborators, institutions, hot topics, and future research trends that will inform potential future directions., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Wang et al.)

We present the development of SpeCamX, a mobile application that enables an unmodified smartphone into a multispectral imager. Multispectral imaging provides detailed spectral information about objects or scenes, but its accessibility has been limited due to its specialized requirements for the device. SpeCamX overcomes this limitation by utilizing the RGB photographs captured by smartphones and converting them into multispectral images spanning a range of 420 to 680 nm without a need for internal modifications or external attachments. The app also includes plugin functions for extracting medical information from the resulting multispectral data cube. In a clinical study, SpeCamX was used to implement an augmented smartphone bilirubinometer, predicting blood bilirubin levels (BBL) with superior performance in accuracy, efficiency and stability compared to default smartphone cameras. This innovative technology democratizes multispectral imaging, making it accessible to a wider audience and opening new possibilities for both medical and non-medical applications., Competing Interests: Authors declare that they have no competing interests., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

We report a method and system of micro-motion imaging (µMI) to realize non-contact measurement of neck pulses. The system employs a 16-bit camera to acquire videos of the neck skin, containing reflectance variation caused by the neck pulses. Regional amplitudes and phases of pulse-induced reflection variation are then obtained by applying a lock-in amplification algorithm to the acquired videos. Composite masks are then generated using the raw frame, amplitude and phase maps, which are then used to guide the extraction of carotid pulse (CP) and jugular vein pulse (JVP) waveforms. Experimental results sufficiently demonstrate the feasibility of our method to extract CP and JVP waves. Compared with conventional methods, the proposed strategy works in a non-contact, non-invasive and self-guidance manner without a need for manual identification to operate, which is important for patient compliance and measurement objectivity. Considering the close relationship between neck pulses and cardiovascular diseases, for example, CA stenosis, the proposed µMI system and method may be useful in the development of early screening tools for potential cardiovascular diseases., Competing Interests: The authors declare no conflict of interest at the current stage of development., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

The reliability of autonomous driving sensing systems impacts the overall safety of the driving system. However, perception system fault diagnosis is currently a weak area of research, with limited attention and solutions. In this paper, we present an information-fusion-based fault-diagnosis method for autonomous driving perception systems. To begin, we built an autonomous driving simulation scenario using PreScan software, which collects information from a single millimeter wave (MMW) radar and a single camera sensor. The photos are then identified and labeled via the convolutional neural network (CNN). Then, we fused the sensory inputs from a single MMW radar sensor and a single camera sensor in space and time and mapped the MMW radar points onto the camera image to obtain the region of interest (ROI). Lastly, we developed a method to use information from a single MMW radar to aid in diagnosing defects in a single camera sensor. As the simulation results show, for missing row/column pixel failure, the deviation typically falls between 34.11% and 99.84%, with a response time of 0.02 s to 1.6 s; for pixel shift faults, the deviation range is between 0.32% and 9.92%, with a response time of 0 s to 0.16 s; for target color loss, faults have a deviation range of 0.26% to 2.88% and a response time of 0 s to 0.05 s. These results prove the technology is effective in detecting sensor faults and issuing real-time fault alerts, providing a basis for designing and developing simpler and more user-friendly autonomous driving systems. Furthermore, this method illustrates the principles and methods of information fusion between camera and MMW radar sensors, establishing the foundation for creating more complicated autonomous driving systems.

Knowledge about global patterns of the decomposition kinetics of distinct soil organic matter (SOM) pools is crucial to robust estimates of land-atmosphere carbon fluxes under climate change. However, the current Earth system models often adopt globally-consistent reference SOM decomposition rates (k ref ), ignoring effects from edaphic-climate heterogeneity. Here, we compile a comprehensive set of edaphic-climatic and SOM decomposition data from published incubation experiments and employ machine-learning techniques to develop models capable of predicting the expected sizes and k ref of multiple SOM pools (fast, slow, and passive). We show that soil texture dominates the turnover of the fast pools, whereas pH predominantly regulates passive SOM decomposition. This suggests that pH-sensitive bacterial decomposers might have larger effects on stable SOM decomposition than previously believed. Using these predictive models, we provide a 1-km resolution global-scale dataset of the sizes and k ref of these SOM pools, which may improve global biogeochemical model parameterization and predictions., (© 2023. The Author(s).)

There are only six isolated living giant panda populations, and a comprehensive understanding of their genetic health status is crucial for the conservation of this vulnerable species. Liangshan Mountains is one of the main distribution areas of living giant pandas and is outside the newly established Giant panda national park. In this study, 971 giant panda fecal samples were collected in the heartland of Liangshan Mountains (Mabian Dafengding Nature Reserve: MB; Meigu Dafengding Nature Reserve: MG; and Heizhugou Nature Reserve: HZG). Microsatellite markers and mitochondrial D-loop sequences were used to estimate population size and genetic diversity. We identified 92 individuals (MB: 27, MG: 22, HZG: 43) from the three reserves. Our results showed that: (1) genetic diversity of three giant panda populations was moderate; (2) several loci deviated significantly from the Hardy-Weinberg equilibrium and almost all these deviated loci showed significant heterozygote deficiencies and inbreeding; (3) three giant panda populations have substantial genetic differentiation with the most differentiation between MB and the two other populations; and (4) a large amount of giant panda feces outside the three reserves were found, implying the existence of protection gap. These results indicated that under stochastic events, the giant panda populations in Liangshan Mountains are at risk of genetic decline or extinction and urgent need of human management. This study revealed that high attention should be paid to the protection of these giant panda populations outside the Giant panda national park, to ensure their survival in their distribution areas., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

The Heilongjiang brown frog (Rana amurensis) is widely used in traditional Chinese medicine. In particular, the oviduct and skin have been developed into various health products. However, limited numbers of complete genomes of amphibian species have been reported, excluding the Heilongjiang brown frog. Here, the transcriptomes of 45 samples from the liver, spleen, heart, ovaries, thigh muscles, skin, oviduct, stomach and intestine of five Heilongjiang brown frog were reassembled and analyzed. A total of 1,085,532 unigenes with an average length of 676.6 bp and N50 of 722 bp were obtained. Comparative transcriptomics of different tissues detected tissue-specific expression. There were 3248 differentially expressed genes (DEGs) in the ovary, and the number of unique DEGs between the ovary and spleen was the largest. The results of DEGs enrichment showed there were many pathways and items related to protein synthesis and metabolism in the oviduct. The DEGs of the skin were enriched with many bacterial defense items, indicating that there were a large number of antimicrobial peptides in the skin. Thus, these were suitable as biological sources for the development and extraction of antimicrobial peptides. Through the assembly of transcriptome sequencing data and functional annotation of the Heilongjiang brown frog genome, this study provides reference materials for further exploring and utilizing functional gene resources of frogs and lays a foundation for medical research and the development of new products., (© 2022. The Author(s).)

The retrovirus human immunodeficiency virus-1 (HIV-1) is the causative agent of AIDS. Although treatment of HIV/AIDS with antiretroviral therapy provides suppression of viremia, latent reservoirs of integrated proviruses preclude cure by current antiviral treatments. Understanding the mechanisms of host-viral interactions may elucidate new treatment strategies. Here, we performed a CRISPR/Cas9 transcriptional activation screen using a high-complexity, genome-wide sgRNA library to identify cellular factors that inhibit HIV-1 infection of human CD4+ T cells. MT4 cells were transduced with a CRISPR/Cas9 sgRNA library and infected with nef-deficient HIV-1NL4-3 expressing ganciclovir-sensitive thymidine kinase, thus enabling selection of HIV-1-resistant cells for analysis of enriched sgRNAs. After validation of screen hits, multiple host factors essential for HIV-1 infection were identified, including SET (SET nuclear proto-oncogene) and ANP32A (acidic nuclear phosphoprotein 32A, PP32A), which together form a histone acetylase inhibitor complex. Using multiple human cell lines and peripheral blood mononuclear cells (PBMCs) from healthy donors and HIV-1-infected individuals, we demonstrate that SET depletion increased HIV-1 infectivity by augmenting DNA integration without significantly changing sites of integration. Conversely, SET overexpression decreased HIV-1 integration and infectivity. SET protein expression was significantly reduced in PBMCs from HIV-1-infected individuals and was downregulated by HIV-1 infection of healthy donor cells in vitro. Notably, HIV-1-induced downregulation of SET could be alleviated by inhibition of the protease granzyme A. Altogether, we have identified cellular inhibitors of HIV-1 infection on a genome-wide scale, which affords new insight into host-virus interactions and may provide new strategies for HIV-1 treatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Patrinia scabra Bunge is a well-known herbal medicine for its favorable treatment on inflammatory diseases owing to its effective ingredients, in which iridoid glycoside plays an extremely significant role. This article aimed to improve the content of total iridoid glycosides in crude extract through a series optimization of extraction procedure. Moreover, considering that both pain and inflammation are two correlated responses triggered in response to injury, irritants or pathogen, the article investigated the anti-inflammatory and analgesic activities of P. scabra to screen out the active fraction., Method: P. scabra was extracted by ultrasonic-microwave synergistic extraction (UMSE) to obtain total iridoid glycosides (PSI), during which a series of conditions were investigated based on single-factor experiments. The extraction process was further optimized by a reliable statistical method of response surface methodology (RSM). The elution fractions of P. scabra extract were prepared by macroporous resin column chromatography. Through the various animal experiment including acetic acid-induced writhing test, formalin induced licking and flinching, carrageenan-induced mice paw oedema test and xylene-induced ear edema in mice, the active fractions with favorable analgesic and anti-inflammatory effect were reasonably screen out., Results: The content of PSI could reach up to 81.42 ± 0.31 mg/g under the optimum conditions as follows: ethanol concentration of 52%, material-to-liquid ratio of 1:18 g/mL, microwave power at 610 W and extraction time of 45 min. After gradient elution by the macroporous resin, the content of PSI increased significantly. Compared with other concentrations of elution liquid, the content of PSI in 30 and 50% ethanol eluate was increased to reach 497.65 and 506.90 mg/g, respectively. Owing to the pharmacology experiment, it was reasonably revealed that 30 and 50% ethanol elution fractions of P. scabra could relieve pain centrally and peripherally, exhibiting good analgesic and anti-inflammatory activities., Conclusion: Patrinia scabra possessed rich iridoids and exhibited significant analgesic and anti-inflammatory activities., (© 2022. The Author(s).)

N 6 ,2'-O-dimethyladenosine (m 6 Am) is an abundant RNA modification located adjacent to the 5'-end of the mRNA 7-methylguanosine (m 7 G) cap structure. m 6 A methylation on 2'-O-methylated A at the 5'-ends of mRNAs is catalyzed by the methyltransferase Phosphorylated CTD Interacting Factor 1 (PCIF1). The role of m 6 Am and the function of PCIF1 in regulating host-pathogens interactions are unknown. Here, we investigate the dynamics and reprogramming of the host m 6 Am RNA methylome during HIV infection. We show that HIV infection induces a dramatic decrease in m 6 Am of cellular mRNAs. By using PCIF1 depleted T cells, we identify 2237 m 6 Am genes and 854 are affected by HIV infection. Strikingly, we find that PCIF1 methyltransferase function restricts HIV replication. Further mechanism studies show that HIV viral protein R (Vpr) interacts with PCIF1 and induces PCIF1 ubiquitination and degradation. Among the m 6 Am genes, we find that PCIF1 inhibits HIV infection by enhancing a transcription factor ETS1 (ETS Proto-Oncogene 1, transcription factor) stability that binds HIV promoter to regulate viral transcription. Altogether, our study discovers the role of PCIF1 in HIV-host interactions, identifies m 6 Am modified genes in T cells which are affected by viral infection, and reveals how HIV regulates host RNA epitranscriptomics through PCIF1 degradation., (© 2021. The Author(s).)

A large body of academic research has recently focused on omnichannel retailing especially on brick-and-mortar (offline) retailers adding and integrating online capabilities. Relatedly, trade press has highlighted how offline retailers have been investing heavily in the use of their existing physical retail network for quicker delivery and pick-up of online orders. Looking at the competition between Amazon and Walmart, however, we demonstrate that focusing on quicker delivery is not the best strategy for offline retailers when opening online channels to compete with online retailers. We estimate a multivariate probit model using data from a customer survey and find that offline retailers should instead focus on delivering the fundamentals of retailing to their online customers too - larger assortment, competitive prices, and purchase convenience. Further, we employ cluster analysis to show which demographics are good targets for retailers as they develop omnichannel capabilities, as well as which demographics retailers need to keep loyal to their original channels., (© 2020 Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and has spread across the globe. SARS-CoV-2 is a highly infectious virus with no vaccine or antiviral therapy available to control the pandemic; therefore, it is crucial to understand the mechanisms of viral pathogenesis and the host immune responses to SARS-CoV-2. SARS-CoV-2 is a new member of the betacoronavirus genus like other closely related viruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Both SARS-CoV and MERS-CoV have caused serious outbreaks and epidemics in the past eighteen years. Here, we report that one of the interferon-stimulated genes (ISGs), cholesterol 25-hydroxylase (CH25H), is induced by SARS-CoV-2 infection in vitro and in COVID-19-infected patients. CH25H converts cholesterol to 25-hydrocholesterol (25HC) and 25HC shows broad anti-coronavirus activity by blocking membrane fusion. Furthermore, 25HC inhibits USA-WA1/2020 SARS-CoV-2 infection in lung epithelial cells and viral entry in human lung organoids. Mechanistically, 25HC inhibits viral membrane fusion by activating the ER-localized acyl-CoA:cholesterol acyltransferase (ACAT) which leads to the depletion of accessible cholesterol from the plasma membrane. Altogether, our results shed light on a potentially broad antiviral mechanism by 25HC through depleting accessible cholesterol on the plasma membrane to suppress virus-cell fusion. Since 25HC is a natural product with no known toxicity at effective concentrations, it provides a potential therapeutic candidate for COVID-19 and emerging viral diseases in the future., (© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Staphylococcus aureus can cause different types of diseases from mild skin infections to life-threatening sepsis worldwide. Owing to the emergence and transmission of multidrug-resistant strains, developing an impactful immunotherapy especially vaccine control approach against S. aureus infections is increasingly encouraged and supported. S. aureus manganese transport protein C (MntC), which is a highly-conserved cell surface protein, can elicit protective immunity against S. aureus and Staphylococcus epidermidis. In this study, we evaluated the humoral immune response and CD4 + T cell-mediated immune responses in a mouse peritonitis model. The results showed that MntC-specific antibodies conferred an essential protection for mice to reduce invasion of S. aureus, which was corroborated via the opsonophagocytic killing assay and passive immunization experiment in mice, and moreover MntC-induced Th17 played a remarkable part in preventing S. aureus infection since the MntC-induced protective immunity decreased after neutralization of IL-17 by antibody in vivo and the Th17 adoptive transferred-mice could partly resist S. aureus challenge. In conclusion, we considered that the MntC-specific antibodies and MntC-specific Th17 cells play cooperative roles in the prevention of S. aureus infection.

Aim: This meta-analysis was conducted to evaluate the diagnostic and prognostic functions of E-cadherin expression in cervical cancer., Methods: PubMed and other databases were searched for articles associated with E-cadherin and cervical cancer. These articles were published before June 2015 and written in English or Chinese. Random-effects model was used to pool odds ratios on the heterogeneity test in the meta-analysis., Results: All of 20 studies were analyzed, in which 522 (42.6%) subjects exhibited reduced E-cadherin expression. Evaluation of clinicopathologic features showed that the downregulation of E-cadherin was related to the overall survival, clinicopathological parameters and age., Conclusion: Downregulation of E-cadherin in cervical cancer patients showed poor overall survival. Therefore, E-cadherinmay be a metastasis-suppressor gene in cervical cancer.

Aggressive angiomyxoma (AAM) is a rare benign mesenchymal tumor that occurs almost exclusively in the soft tissues of the pelvis and perineum. Very few cases of AAM occurring outside these regions have been reported. The present report presents a case of AAM originating from the liver of a 50-year-old female patient. Tumor resection was performed, and pathological examination revealed microscopic features that were characteristic of AAM. Histopathological examination showed that the tumor was composed of scattered spindle-or stellate-shaped cells with thick-walled blood vessels lying in a myxoid stroma. Immunohistochemically, the tumor cells stained positively for CD34, vimentin, and actin. In this paper, we also discuss the differential diagnosis of AAM. To the best of our knowledge, this study is the first to report a case of AAM originating from the liver.

Background: T follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate humoral immune responses. This study examined whether the frequency of CD4(+)CXCR5(+) TFH cells could be associated with active immunity in chronic hepatitis B (CHB) patients., Methodology and Findings: The frequencies of peripheral blood CD4(+)CXCR5(+) TFH cells, inducible T cell costimulator (ICOS), and/or programmed death 1 (PD-1) positive CD4(+)CXCR5(+) TFH cells in immune-active (IA), immune-tolerant (IT) CHB, and healthy controls (HC) were characterized by flow cytometry analysis. The effect of adevofir dipivoxil treatment on the frequency of CD4(+)CXCR5(+) TFH cells, the concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-21, ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb and HBV loads in IA patients were determined. The potential association of the frequency of CD4(+)CXCR5(+) TFH cells with clinical measures was analyzed. In addition, the frequency of splenic and liver CD4(+)CXCR5(+) TFH cells in HBV-transgenic mice was examined. We found that the frequency of CD4(+)CXCR5(+) TFH cells in IA patients was significantly higher than that of IT patients and HC, and the percentages of CD4(+)CXCR5(+) TFH in IA patients were positively correlated with AST. Furthermore, the percentages of ICOS(+), PD-1(+), and ICOS(+)PD-1(+) in CD4(+)CXCR5(+) TFH cells in CHB patients were significantly higher than that of HC. Treatment with adefovir dipivoxil reduced the frequency of CD4(+)CXCR5(+) TFH, PD-1(+)CD4(+)CXCR5(+) TFH cells and the concentrations of HBsAg and HBeAg, but increased the concentrations of HBsAb, HBeAb, IL-2 and IFN-γ in IA patients. Moreover, the frequency of splenic and liver CD4(+)CXCR5(+) TFH cells in HBV-transgenic mice was higher than that of wild-type controls., Conclusions: These data indicate that CD4(+)CXCR5(+) TFH cells may participate in the HBV-related immune responses and that high frequency of CD4(+)CXCR5(+) TFH cells may be a biomarker for the evaluation of active immune stage of CHB patients.

Objective: To establish an HPLC method for determination of catalpol in CSF (cerebrospinal fluid) of rats., Method: Rats were intravenously injected 1.0 g x L(-1) catalpol physiological saline, and the sample of CSF from subarachnoid space of the cerebrum 40 minutes of injection. The sample of CSF from normal rats was used for blank control, the all samples were preserved in a refrigerator of - 20 degrees C, and use HPLC was employed to determine the catalpol content. The separation of catalpol was performed on Hypersil C18 reversion phase chromatographic column. The mobile phase consisted of water-acetonitrile (99.5: 0.5) with a flow rate of 1.0 mL x min(-1) and detection wavelength of 210 nm., Result: The linear range of catalpol in CSF was 0.5-40 mg x L(-1) (r = 0.999 7). The absolute recoveries were (90.2 +/- 1.71)%, (89.1 +/- 1.17)% and (86.9 +/- 0.98)%; and the methodological recoveries were (99.8 +/- 1.98)%, (101.1 +/- 3.04)%, (100.1 +/- 2.30)% respectively. The within-day and between-day derivation RSD were less than 4%. Catalpol was stable in a refrigerator of -20 degrees C for 15 days., Conclusion: The method is simple and accurate for the determination of the content of catalpol in CSF.