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Abstract Background Viral antigen detection test is the most common method used to detect viruses in the field rapidly. However, due to the low sensitivity, it can only be used as an auxiliary diagnosis method for virus infection. Improving sensitivity is crucial for developing more accurate viral antigen tests. Nano luciferase (Nluc) is a sensitive reporter that has not been used in virus detection. Results In this study, we produced an intracellularly Nluc labeled detection antibody (Nluc-ch2C5) and evaluated its ability to improve the detection sensitivity of respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. Compared with the traditional horse-radish peroxidase (HRP) labeled antibody (HRP-ch2C5), Nluc-ch2C5 was 41 times more sensitive for inactivated SARS-CoV-2 virus by sandwich chemiluminescence ELISA. Then we applied Nluc-ch2C5 to establish an automatic magnet chemiluminescence immune assay (AMCA) for the SARS-CoV-2 viral spike protein, the limit of detection was 68 pfu/reaction. The clinical sensitivity and specificity reached 75% (24/32) and 100% (48/48) using 32 PCR-positive and 48 PCR-negative swab samples for clinical evaluation, which is more sensitive than the commercial ELSA kit and colloid gold strip kit. Conclusions Here, monoclonal antibody ch2C5 served as a model antibody and the SARS-CoV-2 served as a model pathogen. The Nluc labeled detecting antibody (Nluc-ch2C5) significantly improved the detection sensitivity of SARS-CoV-2 antigen. This labeling principle applies to other viral infections, so this labeling and test format could be expected to play an important role in detecting other virus antigens.

Abstract Background The mTOR signaling pathway plays an important role in cancer. As a master regulator, the status of MTOR affects pathway activity and the efficacy of mTOR inhibitor therapy. However, little research has been performed to explore MTOR in colorectal cancer (CRC). Methods In this study, gene expression and clinical data were analyzed using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Signaling pathways related to MTOR in CRC were identified by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Somatic mutation data were downloaded from TCGA and analyzed using the maftools R package. Tumor Immune Estimation Resource (TIMER) and CIBERSORT were used to analyze correlations between MTOR and tumor-infiltrating immune cells (TIICs). Finally, we detected MTOR mutations in a CRC cohort from our database using whole-exome sequencing. Results We found that MTOR was overexpressed in Asian CRC patients and associated with a poor prognosis. Enrichment analysis showed that MTOR was involved in metabolism, cell adhesion, and translation pathways in CRC. High MTOR expression was correlated with high tumor mutation burden (TMB) and several TIICs. Finally, we found that the mTOR signaling pathway was activated in CRC lines characterized by microsatellite instability (MSI), and the frequency of MTOR mutations was higher in MSI-high (MSI-H) patients than in microsatellite stable (MSS) patients. Conclusions MTOR may represent a comprehensive indicator of prognosis and immunological status in CRC. The genomic signatures of MTOR may provide guidance for exploring the role of mTOR inhibitors in CRC.

Bovine parainfluenza virus type 3 (BPIV-3) is one of the major pathogens of the bovine respiratory disease complex (BRDC). BPIV-3 surveillance in China has been quite limited. In this study, we used PCR to test 302 cattle in China, and found that the positive rate was 4.64% and the herd-level positive rate was 13.16%. Six BPIV-3C strains were isolated and confirmed by electron microscopy, and their titers were determined. Three were sequenced by next-generation sequencing (NGS). Phylogenetic analyses showed that all isolates were most closely related to strain NX49 from Ningxia; the genetic diversity of genotype C strains was lower than strains of genotypes A and B; the HN, P, and N genes were more suitable for genotyping and evolutionary analyses of BPIV-3. Protein variation analyses showed that all isolates had mutations at amino acid sites in the proteins HN, M, F, and L. Genetic recombination analyses provided evidence for homologous recombination of BPIV-3 of bovine origin. The virulence experiment indicated that strain Hubei-03 had the highest pathogenicity and could be used as a vaccine candidate. These findings apply an important basis for the precise control of BPIV-3 in China.

The achievement of the low Gilbert damping parameter in spin dynamic modulation is attractive for spintronic devices with low energy consumption and high speed. Metallic ferromagnetic alloy Co-Fe-B is a possible candidate due to its high compatibility with spintronic technologies. Here, we report thickness-dependent damping and soft magnetism in Co-Fe-B films sandwiched between two non-magnetic layers with Co-Fe-B films up to 50 nm thick. A non-monotonic variation of Co-Fe-B film damping with thickness is observed, which is in contrast to previously reported monotonic trends. The minimum damping and the corresponding Co-Fe-B thickness vary significantly among the different non-magnetic layer series, indicating that the structure selection significantly alters the relative contributions of various damping mechanisms. Thus, we developed a quantitative method to distinguish intrinsic from extrinsic damping via ferromagnetic resonance measurements of thickness-dependent damping rather than the traditional numerical calculation method. By separating extrinsic and intrinsic damping, each mechanism affecting the total damping of Co-Fe-B films in sandwich structures is analyzed in detail. Our findings have revealed that the thickness-dependent damping measurement is an effective tool for quantitatively investigating different damping mechanisms. This investigation provides an understanding of underlying mechanisms and opens up avenues for achieving low damping in Co-Fe-B alloy film, which is beneficial for the applications in spintronic devices design and optimization.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry; it is a globally prevalent multifactorial infection primarily caused by viral and bacterial coinfections. In China, Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens associated with BRD. Our previous study attempted to combine the two vaccines and conducted a preliminary investigation of their optimal antigenic ratios. Based on this premise, the research extended its investigation by administering varying vaccine doses in a rabbit model to identify the most effective immunization dosage. After immunization, all rabbits in other immunization dose groups had a normal rectal temperature without obvious clinical symptoms. Furthermore, assays performed on the samples collected from immunized rabbits indicated that there were increased humoral and cellular immunological reactions. Moreover, the histological analysis of the lungs showed that immunized rabbits had more intact lung tissue than their unimmunized counterparts after the challenge. Additionally, there appears to be a positive correlation between the protective efficacy and the immunization dose. In conclusion, the different immunization doses of the attenuated and marker M. bovis HB150 and BoHV-1 gG-/tk- combined vaccine were clinically safe in rabbits; the mix of 2.0 × 108 CFU of M. bovis HB150 and 2.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its highest humoral and cellular immune responses and a more complete morphology of the lung tissue compared with others. These findings determined the optimal immunization dose of the attenuated and marker M. bovis HB150 and BoHV-1 gG-/tk- combined vaccine, laying a foundation for its clinical application.

Background: Since the outbreak of coronavirus disease (COVID-19), the high infection rate and mutation frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent, have contributed to the ongoing global pandemic. Vaccination has become the most effective means of controlling COVID-19. Traditional neutralizing tests of sera are complex and labor-intensive, therefore, a rapid test for detecting neutralizing antibodies and antibody status post-immunization is needed. Methods: Based on the fact that antibodies exhibit neutralizing activity by blocking the binding of the S protein receptor-binding domain (S-RBD) to ACE2, we developed a rapid neutralizing antibody test, ACE2-Block-ELISA. To evaluate the sensitivity and specificity, we used 54 positive and 84 negative serum samples. We also tested the neutralizing activities of monoclonal antibodies (mAbs) and 214 sera samples from healthy individuals immunized with the inactivated SARS-CoV-2 vaccine. Results: The sensitivity and specificity of the ACE2-Block ELISA were 96.3% and 100%, respectively. For neutralizing mAb screening, ch-2C5 was selected for its ability to block the ACE2–S-RBD interaction. A plaque assay confirmed that ch-2C5 neutralized SARS-CoV-2, with NT50 values of 4.19, 10.63, and 1.074 µg/mL against the SARS-CoV-2 original strain, and the Beta and Delta variants, respectively. For the immunized sera samples, the neutralizing positive rate dropped from 82.14% to 32.16% within 4 months post-vaccination. Conclusions: This study developed and validated an ACE2-Block-ELISA to test the neutralizing activities of antibodies. As a rapid, inexpensive and easy-to-perform method, this ACE2-Block-ELISA has potential applications in rapid neutralizing mAb screening and SARS-CoV-2 vaccine evaluation.

IntroductionCoronaviruses (CoVs) are naturally found in bats and can occasionally cause infection and transmission in humans and other mammals. Our study aimed to build a deep learning (DL) method to predict the adaptation of bat CoVs to other mammals.MethodsThe CoV genome was represented with a method of dinucleotide composition representation (DCR) for the two main viral genes, ORF1ab and Spike. DCR features were first analyzed for their distribution among adaptive hosts and then trained with a DL classifier of convolutional neural networks (CNN) to predict the adaptation of bat CoVs.Results and discussionThe results demonstrated inter-host separation and intra-host clustering of DCR-represented CoVs for six host types: Artiodactyla, Carnivora, Chiroptera, Primates, Rodentia/Lagomorpha, and Suiformes. The DCR-based CNN with five host labels (without Chiroptera) predicted a dominant adaptation of bat CoVs to Artiodactyla hosts, then to Carnivora and Rodentia/Lagomorpha mammals, and later to primates. Moreover, a linear asymptotic adaptation of all CoVs (except Suiformes) from Artiodactyla to Carnivora and Rodentia/Lagomorpha and then to Primates indicates an asymptotic bats-other mammals-human adaptation.ConclusionGenomic dinucleotides represented as DCR indicate a host-specific separation, and clustering predicts a linear asymptotic adaptation shift of bat CoVs from other mammals to humans via deep learning.

Understanding the effect of environmental factors on the net ecosystem CO2 exchange (NEE) and the response of NEE to rainfall events is of great significance for an accurate understanding of the carbon cycle for desert steppe ecosystems. Based on the long-term (2011–2018) eddy covariance flux data of a temperate desert steppe in Inner Mongolia, China, this study used path analysis to analyze the combined impact of the environmental factors on NEE. The results showed that during the growing season, vapor pressure deficit (VPD) and soil water content (SWC) was the most prominent environmental factor for the daytime NEE and nighttime NEE, respectively. NEE responds differently to individual environmental factors among multi-year climatic conditions. The size of rainfall event has significant impacts on NEE, it can effectively promote the CO2 uptake of the desert steppe ecosystem when rainfall event size is greater than 5 mm, and the NEE response increased with the rainfall event size. Moreover, NEE peaked approximately 1–3 days after a 5–10 mm rainfall event, while the rainfall event size >10 mm, it would take 3–5 days for NEE to reach a peak value; and yet, small rainfall events (< 5 mm) slightly increased CO2 emissions. During the growing season, carbon uptake increased with monthly rainfall, except in May. Our results are important for understanding the carbon cycle and its control mechanisms in the temperate desert steppe of Inner Mongolia.

Abstract As for the voltage‐controlled voltage sources converter (VSC), the inner current loop of dual closed‐loop control is equivalent to a virtual impedance, which provides effective damping for the system. However, the time delay caused by computation and transmission becomes increasingly prominent in the low‐pulse‐ratio cases, which not only limits the achievable bandwidth, but also reduces the stability of the current loop. This paper proposes an enhanced control strategy for current loop by adding the feedback of computation delay into the current controller, to significantly widen the stability region and control bandwidth, and increase the active damping. The parameter design of the current controller is presented based on discrete‐time root locus. Subsequently, the voltage controller is directly deduced in the discrete‐time domain, which eliminates the poles/zeros deviation caused by discretization. The accurate delay compensation is realized by pole‐zero cancellation, thus avoiding the additional phase compensation for fundamental and harmonic frequencies. Simulation and experimental results validate the effectiveness of the enhanced dual‐loop control strategy.

This paper announces a novel three-dimensional chaotic system with line equilibrium and discusses its dynamic properties such as Lyapunov exponents, phase portraits, equilibrium points, bifurcation diagram, multistability and coexisting attractors. New synchronization results based on integral sliding mode control (ISMC) are also derived for the new chaotic system with line equilibrium. In addition, an electronic circuit implementation of the new chaotic system with line equilibrium is reported and a good qualitative agreement is exhibited between the MATLAB simulations of the theoretical model and the MultiSim results. We also display the implementation of the Field-Programmable Gate Array (FPGA) based Pseudo-Random Number Generator (PRNG) by using the new chaotic system. The throughput of the proposed FPGA based new chaotic PRNG is 462.731 Mbps. Randomness analysis of the generated numbers has been performed with respect to the NIST-800-22 tests and they have successfully passed all of the tests. Finally, an image encryption algorithm based on the pixel-level scrambling, bit-level scrambling, and pixel value diffusion is proposed. The experimental results show that the encryption algorithm not only shuffles the pixel positions of the image, but also replaces the pixel values with different values, which can effectively resist various attacks such as brute force attack and differential attack.

The amount of cultivated land per capita in China is relatively low, and the phenomenon of non-cultivated land (NCL) in recent years has negatively impacted the stability of grain production in China. In this study, long-time series images obtained via satellite remote sensing were used to monitor spatio-temporal changes in NCL at the county scale. Seven-phase images were acquired from 1990 to 2020 (every five years) using medium-resolution Landsat MSS, TM, ETM+, and Sentinel MSI. Vegetation indices and texture features were extracted for all images. Terrain features such as slope, aspect and elevation were extracted from the DEM data. Combining vegetation index features, texture features, terrain features and multispectral bands, the image classification was performed using the random forest (RF) algorithm. The indices of classification accuracy assessment indices included overall accuracy (OA) and multiclass F-scores (Fm). Zonal statistics were used to calculate the area of cultivated land in towns for 1990 and 2020, and to create grades for the reduction of cultivated land. Finally, indicators including land use dynamic degree (LUDD), land use type change (LUTC) and land use change rate (LUCR) were adopted to reflect the spatio-temporal of NCL in the study area. The results show that RF classification algorithm achieves accurate and efficient land use extraction. The OA were greater than 86%, and the Fm were over 0.88. The cultivated land area in the study area showed decreasing trend. From 1990 to 2020, the ratio of cultivated land decreased from 59.75% to 50.21%. Meanwhile, the dynamic degree of cultivated land increased annually. The conversion of cultivated land into construction land was dominant, accounting for 31.84% of the total change in cultivated land over the past 30 years. This study also reveals that NCL is highly related to local economic and land-use policies. Multi-source remote sensing data have been used to quantitatively analyse the spatio-temporal changes in cultivated land conversion, providing a reference for relevant land management departments to master cultivated land use changes and adjust land management policies.

BackgroundCuprotosis is a novel form of programmed cell death that involves direct targeting of key enzymes in the tricarboxylic acid (TCA) cycle by excess copper and may result in mitochondrial metabolic dysfunction. However, whether cuprotosis may mediate the tumor microenvironment (TME) and immune regulation in colorectal cancer (CRC) remains unclear.MethodsTen cuprotosis-related genes were selected and unsupervised consensus clustering was performed to identify the cuprotosis patterns and the correlated TME characteristics. Using principal component analysis, a COPsig score was established to quantify cuprotosis patterns in individual patients. The top 9 most important cuprotosis signature genes were analyzed using single-cell transcriptome data.ResultsThree distinct cuprotosis patterns were identified. The TME cell infiltration characteristics of three patterns were associated with immune-excluded, immune-desert, and immune-inflamed phenotype, respectively. Based on individual cuprotosis patterns, patients were assigned into high and low COPsig score groups. Patients with a higher COPsig score were characterized by longer overall survival time, lower immune cell as well as stromal infiltration, and greater tumor mutational burden. Moreover, further analysis demonstrated that CRC patients with a higher COPsig score were more likely to respond to immune checkpoint inhibitors and 5-fluorouracil chemotherapy. Single-cell transcriptome analysis indicated that cuprotosis signature genes recruited tumor-associated macrophages to TME through the regulation of TCA and the metabolism of glutamine and fatty acid, thus influencing the prognosis of CRC patients.ConclusionThis study indicated that distinct cuprotosis patterns laid a solid foundation to the explanation of heterogeneity and complexity of individual TME, thus guiding more effective immunotherapy as well as adjuvant chemotherapy strategies.

Background: Cerebral ischemia is one of the leading causes of neurological deficit, dementia, and disability globally. Salvianolic acids for injection (SAFI), a multi-component drug derived from Salvia miltiorrhiza L., has been clinically used in China to treat ischemic stroke. Purpose: This study was designed to investigate the mechanisms of SAFI in alleviating cerebral ischemia-induced neurodegeneration, especially its regulatory effects on excessive ER stress. Basic procedures: The rat acute cerebral ischemic injury model was established by a 1.5 h occlusion of the middle cerebral artery followed by 24 h of reperfusion. The neurological deficits, neurobehavior, cerebral infarct volume and edema of rats were examined. Hematoxylin and eosin staining, transmission electron microscopy analysis and TUNEL staining were performed to study the brain injury and cell apoptosis. Western blot and immunofluorescence assay were carried out to study the effects and mechanism of SAFI on ischemic injury. Main findings: Results showed that SAFI significantly inhibited the acute neurodegeneration, reduced brain infarct volumes and decreased brain water content of rats. SAFI also downregulated the relative protein levels of Bax/Bcl-2, Bim, Caspase-12, and reduced the number of TUNEL-positive cells in brain tissue, indicating the anti-apoptotic effects of SAFI. Both of immunofluorescence assay and western blot results showed that SAFI downregulated the expression of endoplasmic reticulum (ER) stress maker GRP78. SAFI dramatically inhibited the ER stress-related PERK/eIF2α/ATF4/CHOP and IRE1α/TRAF2/ASK1/JNK signaling pathways. SAFI also alleviated NF-κB triggered inflammatory response, and inhibited the production of IL-6 and IL-β. Conclusions: Our studies indicated that inhibition of excessive ER stress contributes to the protective effects of SAFI against cerebral ischemia-induced neurodegeneration and neuroinflammation.

BackgroundAcceptability and perception of the COVID-19 vaccine among different social groups have been the subject of several studies. However, little is known about foreign medical students in Chinese universities.AimThis study, therefore, fills the literature gap using a focus group technique to assess the acceptance and perception of the COVID-19 vaccine among foreign medical students in China.MethodsThe study adopted an online cross-sectional survey method following the Chinese universities' lockdowns to collect the data between March and April 2022. A data collection questionnaire was developed, and then the link was shared with the respondents through key informants in different universities in China to obtain the data. The data collection process only included foreign medical students who were in China from May 2021 to April 2022. The authors received a total of 403 responses from the respondents. During data processing, we excluded 17 respondents since they were not in China while administering the questionnaire to enhance the data validity. The authors then coded the remaining 386 respondents for the estimation process. We finally applied the multilinear logistics regression technique to model the COVID-19 vaccine acceptance with the response or influencing factors, including the mediating factors among the foreign medical students in China.ResultsThe data statistics show that 4.9% of the respondents were younger than 20 years, 91.5% were 20–40 years old, and 3.6% were older than 40 years; 36.3% of respondents were female subjects and 63.7% were male subjects. The results also show that the respondents are from six continents, including the African continent, 72.4%, Asia 17.4%, 3.1% from Europe, 2.8% from North America, 1.6% from Australia, and 2.3% from South America. The mediation analysis for the gender variable (β = 0.235, p = 0.002) suggests that gender is a significant channel in COVID-19 vaccine acceptance and perception among foreign medical students in China. Also, the main analysis shows that opinion on the safety of the vaccine (β = 0.081, p = 0.043), doses of the vaccine to receive (β = 0.175, p = 0.001), vaccine safety with some side effects (β = 0.15, p = 0.000), and the possibility of acquiring COVID-19 after vaccination (β = 0.062, p = 0.040) are all positive factors influencing vaccine acceptability and perception. Also, the home continent (β = −0.062, p = 0.071) is a negative factor influencing COVID-19 vaccine acceptance and perception. Furthermore, the finding shows that fear perceptions has affected 200 (51.81%) respondents. The medical students feared that the vaccines might result in future implications such as infertility, impotence, and systemic health conditions such as cardiovascular, respiratory, or deep vein thrombosis. In addition, 186 (48.19%) students feared that the vaccines were intended to shorten life expectancy.ConclusionCOVID-19 vaccination acceptability and perception among medical students in China is high, most predominantly due to their knowledge of medicine composition formulation. Despite widespread acceptance by the general public and private stakeholders, we concluded that vaccination resistance remains a significant factor among medical students and trainees. The study further adds that in considering the COVID-19 vaccine, the factor of the home continent plays a significant role in vaccine hesitancy among foreign medical students. Also, knowledge, information, and education are important pillars confronting new medicine administered among medical trainees. Finally, there is a low rate of COVID-19 vaccine hesitancy among foreign medical students in China. The study, therefore, recommends targeted policy strategies, including sensitization, detailed public information, and education, especially for medical colleges and institutions on the COVID-19 vaccination, to achieve 100%. Furthermore, the study recommends that future researchers explore other factors influencing accurate information and education for successful COVID-19 vaccination implementation.

BackgroundWhite matter hyperintensities (WMH) are a key imaging feature of cerebral small-vessel disease (CSVD). However, there is a lack of standardized methods for determining WMH volume, and the value of total white matter (WM) volume in the assessment of cognitive impairment in patients with CSVD remains unknown.ObjectiveWe aimed to explore the correlations of WMH volume and WM volume with cognitive dysfunction and its components in patients with CSVD. We also aimed to compare the value of the Fazekas score, WMH volume, and ratio of WMH volume to total WM volume in the assessment of cognitive dysfunction.MethodsThe study included 99 patients with CSVD. Patients were categorized into following groups based on MoCA scores: patients with mild cognitive impairment and those without. Brain magnetic resonance images were processed to investigate differences in WMH and WM volumes between the groups. Logistic regression analysis was used to determine whether these two factors were independent risk factors for cognitive dysfunction. Correlation analysis was used to examine the relationships of WMH and WM volume with different types of cognitive impairment. Receiver operating characteristic curves were used to compare the effectiveness of the WMH score, WMH volume, and WMH to WM ratio for evaluating cognitive dysfunction.ResultsThere were significant differences in age, education level, WMH volume, and WM volume between the groups (P < 0.05). After adjusting for age and education, the multivariate logistic analysis indicated that both WMH volume and WM volume were independent risk factors for cognitive dysfunction. Correlation analysis indicated that WMH volume was mainly related to cognition involving the visual space and delayed recall. WM volume was not strongly associated with different types of cognitive dysfunction. The WMH to WM ratio was the strongest predictor, with an area under the curve value of 0.800 and a 95% confidence interval of 0.710–0.891.ConclusionIncreases in WMH volume may aggravate cognitive dysfunction in patients with CSVD, and a higher WM volume may reduce the effect of WMH volume on cognitive function to a certain extent. The ratio of WMH to total WM volume may reduce the impact of brain atrophy, allowing for more accurate evaluation of cognitive dysfunction in older adults with CSVD.

The ecological water demand (EWD) of natural vegetation is a key issue in regional water resource allocation and ecosystem management. Although the evaluation of the EWD of vegetation has been emphasized in numerous studies, research on the threshold EWD of vegetation, including the minimum and optimum EWD, as well as an effective quantitative analysis framework, are still lacking. Therefore, in this study, the evapotranspiration of natural vegetation in the plain area of the Tarim River Basin over the last22 years was estimated based on remote sensing image data. Additionally, the multi-year dynamics of the EWD of natural vegetation were analyzed. In this study, the concept of “latitude” was adopted from studies of ecosystem resilience, to propose a novel analytical framework to measure the minimum and optimal EWD of natural vegetation in inland arid areas. The results show that the average minimum and optimum EWD of natural vegetation is105.45 and 135.53 mm, respectively. The average minimum EWD of woodland and high- and low-coverage grassland is 129.13, 284.38, and 111.40 mm, respectively, and the mean value of the optimum EWD is 152.96, 382.05, and 141.16 mm, respectively. The novel approach of this study is simple and easy to use, and provides an effective method for quantitative evaluation of the EWD threshold of natural vegetation.

ObjectiveColorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into.MethodsThe expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo.ResultsPKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT.ConclusionThe increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT.

Background: RNA-editing refers to post-transcriptional transcript alterations that lead to the formation of protein isoforms and the progression of various tumors. However, little is known about its roles in gliomas.Aim: The aim of this study is to identify prognosis-related RNA-editing sites (PREs) in glioma, and to explore their specific effects on glioma and potential mechanisms of action.Methods: Glioma genomic and clinical data were obtained from TCGA database and SYNAPSE platform. The PREs was identified with regression analyses and the corresponding prognostic model was evaluated with survival analysis and receiver operating characteristic curve. Functional enrichment of differentially expressed genes between risk groups was performed to explore action mechanisms. The CIBERSORT, ssGSEA, gene set variation analysis, and ESTIMATE algorithms were employed to assess the association between PREs risk score and variations of tumor microenvironment, immune cell infiltration, immune checkpoints, and immune responses. The maftools and pRRophetic packages were used to evaluate tumor mutation burden and predict drug sensitivity.Results: A total of thirty-five RNA-editing sites were identified as prognosis-related in glioma. Functional enrichment implied variation of immune-related pathways between groups. Notably, glioma samples with higher PREs risk score exhibited higher immune score, lower tumor purity, increased infiltration of macrophage and regulatory T cells, suppressed NK cell activation, elevated immune function score, upregulated immune checkpoint gene expression, and higher tumor mutation burden, all of which implied worse response to immune therapy. Finally, high-risk glioma samples are more sensitive to Z-LLNle-CHO and temozolomide, while the low-risk ones respond better to Lisitinib.Conclusion: We identified a PREs signature of thirty-five RNA editing sites and calculated their corresponding risk coefficients. Higher total signature risk score indicates worse prognosis and worse immune response and lower sensitivity to immune therapy. The novel PREs signature could help risk stratification, immunotherapy response prediction, individualized treatment strategy-making for glioma patients, and development of novel therapeutic approaches.

BackgroundNervus intermedius (NI) injuries are not given enough attention by neurosurgeons during vestibular schwannoma (VS) surgery. Preservation of NI function is essential for the integrity and continuity of the facial nerve, although this can be challenging. We identified the risk factors for NI injury and proposed our experience for optimizing NI preservation based on our cases.MethodsWe retrospectively analyzed clinical data from a consecutive series of 127 patients with VS who underwent microsurgery via the retrosigmoid approach from 2017 to 2021 at our institution. The baseline characteristics of the patients were collected from the medical records, and the incidence of NI dysfunction symptoms was obtained by outpatient and online video follow-up 6 months after surgery. The surgical procedures and techniques used were described in detail. The data were analyzed in relation to sex, age, tumor location (left or right), Koos grading scale, internal acoustic canal (IAC) invasion (TFIAC Classification), brainstem adhesion, tumor characteristics (cystic or solid), tumor necrosis, and preoperative House–Brackmann (HB) grading by univariate and multivariate analyses.ResultsGross tumor removal was achieved in 126 (99.21%) patients. Subtotal removal was performed on one patient (0.79%). Twenty-three of our cases exhibited facial nerve palsy preoperatively; 21 patients had HB grade II facial palsy, and two had HB grade III. Two months after surgery, 97 (76.38%) patients had normal function of the motor portion of the facial nerve; 25 (19.69%) patients had HB Grade II facial palsy, five had Grade III (3.94%), and zero (0%) had Grade IV. Postoperatively, 15 patients experienced newly gained dry eyes (11.81%), whereas 21 cases of lacrimal disturbances (16.54%), nine of taste disturbances (7.09%), seven of xerostomia (5.51%), five of nasal hypersecretions (3.94%), and seven of hypersalivation (5.51%) were identified in our cases. Univariate and multivariate analyses revealed that the Koos grading scale and tumor characteristics (solid or cystic) were correlated with NI injury (p

Tumor development is frequently accompanied by abnormal expression of multiple genomic genes, which can be broadly viewed as decreased expression of tumor suppressor genes and upregulated expression of oncogenes. In this process, epigenetic regulation plays an essential role in the regulation of gene expression without alteration of DNA or RNA sequence, including DNA methylation, RNA methylation, histone modifications and non-coding RNAs. Therefore, drugs developed for the above epigenetic modulation have entered clinical use or preclinical and clinical research stages, contributing to the development of antitumor drugs greatly. Despite the efficacy of epigenetic drugs in hematologic caners, their therapeutic effects in solid tumors have been less favorable. A growing body of research suggests that epigenetic drugs can be applied in combination with other therapies to increase efficacy and overcome tumor resistance. In this review, the progress of epigenetics in tumor progression and oncology drug development is systematically summarized, as well as its synergy with other oncology therapies. The future directions of epigenetic drug development are described in detail.

We synthesized a series of modified Co-ZIF-67 materials with tunable morphology to support fine Au nanoparticles for the alkali-free aerobic oxidation of benzyl alcohol. Structure promotion was performed using Stöber silica as a hard template, which was subsequently removed by NaOH etching before gold immobilization. The texture structure of Au/(Si)C was greatly improved with increasing surface area and volume. CoOx was simultaneously introduced into the carbon shell from the Co-ZIF-67 precursor, which consequently facilitated the specific Au-support interaction via bimetallic synergy. XRD, XPS, and TEM images demonstrated the redispersion of both Au and CoOx as well as the electronic delivery between metals. Analysis of the chemical and surface composition suggested a surface rich in Auδ+ with abundant lattice oxygen contributed by CoOx in the final Au/(Si)C, which improved the transformation rate of benzyl alcohol even in an alkali-free condition. Au/(Si)C with finely dispersed Au particles showed excellent catalytic performance in the alkali-free environment, with 89.3% benzyl conversion and 74.5% benzaldehyde yield under very mild conditions.

Boreal forests, the second continental biome on Earth, are known for their massive carbon storage capacity and important role in the global carbon cycle. Comprehending the temporal dynamics and controlling factors of net ecosystem CO2 exchange (NEE) is critical for predicting how the carbon exchange in boreal forests will change in response to climate change. Therefore, based on long-term eddy covariance observations from 2008 to 2018, we evaluated the diurnal, seasonal, and interannual variations in the boreal forest ecosystem NEE in Northeast China and explored its environmental regulation. It was found that the boreal forest was a minor CO2 sink with an annual average NEE of -64.01 (± 24.23) g CO2 m-2 yr-1. The diurnal variation in the NEE of boreal forest during the growing season was considerably larger than that during the non-growing season, and carbon uptake peaked between 8:30 and 9:30 in the morning. The seasonal variation in NEE demonstrated a “U” shaped curve, and the carbon uptake peaked in July. On a half-hourly scale, photosynthetically active radiation and vapor pressure deficit had larger impacts on daytime NEE during the growing season. However, temperature had major control on NEE during the growing season at night and during the non-growing season. On a daily scale, temperature was the dominant factor controlling seasonal variation in NEE. Occurrence of extreme temperature days, especially extreme temperature events, would reduce boreal forest carbon uptake; interannual variation in NEE was substantially associated with the maximum CO2 uptake rate during the growing season. This study deepens our understanding of environmental controls on NEE at multiple timescales and provides a data basis for evaluating the global carbon budget.

At present, the preventive effect of ischemic stroke is not ideal, and the preventive drugs are limited. Danshen, the dried root of Salvia miltiorrhiza Bge, is a common medicinal herb in Traditional Chinese Medicine, which has been used for the treatment of cardiovascular diseases for many years. Phenolic Acids extracted from danshen, which showed multiple biological activities, have been developed as an injection for the treatment of ischemic stroke. However, its preventive effect on ischemic stroke has not been fully reported. The current study aimed to identify the potential active phenolic acids for the prevention of ischemic stroke and explore its mechanism using network pharmacology and experimental analyses. The targets of phenolic acids and ischemic stroke were obtained from public databases. Network pharmacology predicted that 35 kinds of phenolic acids had 201 core targets with ischemic stroke. The core prevention targets of ischemic stroke include IL-6, AKT1, VEGFA, etc. The signaling pathways involved in core targets include AGE-RAGE signaling pathway, HIF-1 signaling pathway, and cAMP signaling pathways, etc. Then, the antiplatelet effect of phenolic acids was screened by in vitro antiplatelet experiment. Our results showed that phenolic acids have a good inhibitory effect on ADP-induced platelet aggregation and salvianolic acid A had a good antiplatelet effect. We further demonstrated that SAA preventive administration reduced neurobehavioral scores, decreased infarct size, and protected tight junction proteins in autologous thrombus stroke model. These studies not only shed light on the potential mechanisms of phenolic acids active components on ischemic stroke, but also provided theoretical and experimental information for the development of new medicines from Danshen for the prevention of ischemic stroke. In addition, our results suggest that SAA has the potential to be a candidate for ischemic stroke prevention drug.

In this paper, a rock dynamic and static triaxial mechanical test system is adopted to conduct triaxial compression failure acoustic emission test on coal rock with outburst-proneness. The purpose is to study the evolution law of the acoustic emission (AE) b value of coal rock under static and dynamic load of varying frequencies. The test results show that the dynamic load disturbance will accelerate the instability failure process of coal rock, that the average stress level/ultimate strain of coal rock decline/rises correspondingly with the increasing dynamic load frequency. Moreover, the overall AE b value after dynamic load disturbance is relatively low, and the higher the dynamic load frequency, the larger the decrease in the b value. In addition, as the dynamic load frequency increases, the AE ringing count and AE energy show a trend of first increasing and then decreasing, and they are negatively correlated with the evolution characteristics of the acoustic emission b value. Furthermore, the change rule of AE b value is closely related to the instability and failure process of coal rock. A second-stage of the overall b value of acoustic emission shows a “cliff jumping type” decrease dip angle or “fault cliff type” decrease dip angle indicates the imminent failure of coal rock, which can be used as an evaluation index for real-time monitoring of dynamic disasters of coal rock with outburst-proneness.

Bovine respiratory disease (BRD) is a global prevalent multifactorial infection primarily caused by viral and bacterial coinfections. In China, Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the predominant pathogens associated with BRD. Our previous study involved the development of attenuated M. bovis HB150 and BoHV-1 gG-/tk- vaccine strains, which were thoroughly assessed for their safety profiles and protective efficacy in cattle. In this study, we applied a combination of vaccines in varying ratios and used a rabbit model to determine the safety and protective efficacy. We used PCR/RT-PCR to detect the postimmunization and challenge shedding of M. bovis and BoHV-1. Additionally, we measured antibody titers and the expression of IFN-β and TNF-α to evaluate the humoral and cellular immune responses, respectively. Furthermore, we performed a histopathological analysis to assess lung damage. Our study provides evidence of the safety and effectiveness of the bivalent M. bovis–BoHV-1 vaccine in rabbits, particularly when applying a combination of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 of the BoHV-1 gG-/tk- strain. The bivalent vaccine significantly enhanced both the long-term antibody immune response and cellular protection against the M. bovis and BoHV-1 challenge. These findings provide a valuable model for the potential application in cattle.

Zinc-finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs), and CRISPR-associated Cas9 endonucleases are three major generations of genome editing tools. However, no parallel comparison about the efficiencies and off-target activity of the three nucleases has been reported, which is critical for the final clinical decision. We for the first time developed the genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) method in ZFNs and TALENs with novel bioinformatics algorithms to evaluate the off-targets. By targeting human papillomavirus 16 (HPV16), we compared the performance of ZFNs, TALENs, and SpCas9 in vivo. Our data showed that ZFNs with similar targets could generate distinct massive off-targets (287–1,856), and the specificity could be reversely correlated with the counts of middle “G” in zinc finger proteins (ZFPs). We also compared the TALENs with different N-terminal domains (wild-type [WT]/αN/βN) and G recognition modules (NN/NH) and found the design (αN or NN) to improve the efficiency of TALEN inevitably increased off-targets. Finally, our results showed that SpCas9 was more efficient and specific than ZFNs and TALENs. Specifically, SpCas9 had fewer off-target counts in URR (SpCas9, n = 0; TALEN, n = 1; ZFN, n = 287), E6 (SpCas9, n = 0; TALEN, n = 7), and E7 (SpCas9, n = 4; TALEN, n = 36). Taken together, we suggest that for HPV gene therapies, SpCas9 is a more efficient and safer genome editing tool. Our off-target data could be used to improve the design of ZFNs and TALENs, and the universal in vivo off-target detection pipeline for three generations of artificial nucleases provided useful tools for genome engineering-based gene therapy.

Abstract Background This study aimed to determine whether ultrasound-guided continuous erector spinae plane block (ESPB) had an effect on opioid consumption and postoperative rehabilitation in patients undergoing video-assisted thoracic surgery (VATS). Methods In this prospective study, 120 patients aged 20–70 years who underwent elective VATS were randomly allocated to one of three groups: group C (general anesthesia with patient-controlled intravenous analgesia [PCIA]), group T (general anesthesia with patient-controlled epidural analgesia [PCEA]), or group E (general anesthesia with continuous ESPB and PCIA). Perioperative opioid consumption, visual analog scale (VAS) scores, preoperative and postoperative Quality of Recovery-15 scores, and postoperative opioid-related adverse events were all assessed. Results Intraoperative sufentanil consumption in groups T and E was significantly lower than that in group C (both P

Hybrid supercapacitors represent a promising candidate for grid-scale energy storage devices because of their excellent high-power density, inherent safety and low cost. Here we report a novel NiSe2@rGO nanocomposite (reduced graphene oxide decorated NiSe2 nanoparticles), which shows high specific capacity of 467 C g−1 at 1 A g−1 and superior rate performance (∼72.8% of the capacity retention at 20 A g−1). Moreover, a hybrid supercapacitor (HSC) assembled from the NiSe2@rGO positive electrode and rGO negative electrode delivers high energy density (34.3 Wh kg−1) and splendid cycling lifespan (∼93% of the capacity retention over 6500 cycles). This study provides a novel insight on high-performance hybrid supercapacitors.

Reversing the thermal induced sintering phenomenon and forming high temperature stable fine dispersed metallic centers is one of the ever-lasting targets in heterogeneous catalysis. Here the authors report the dispersion of metallic Ni particles into under-coordinated two-dimensional Ni clusters over γ-Mo2N.

Malignant tumors are the second leading cause of death worldwide. This is a public health concern that negatively impacts human health and poses a threat to the safety of life. Although there are several treatment approaches for malignant tumors, surgical resection remains the primary and direct treatment for malignant solid tumors. Anesthesia is an integral part of the operation process. Different anesthesia techniques and drugs have different effects on the operation and the postoperative prognosis. Propofol is an intravenous anesthetic that is commonly used in surgery. A substantial number of studies have shown that propofol participates in the pathophysiological process related to malignant tumors and affects the occurrence and development of malignant tumors, including anti-tumor effect, pro-tumor effect, and regulation of drug resistance. Propofol can also reshape the tumor microenvironment, including anti-angiogenesis, regulation of immunity, reduction of inflammation and remodeling of the extracellular matrix. Furthermore, most clinical studies have also indicated that propofol may contribute to a better postoperative outcome in some malignant tumor surgeries. Therefore, the author reviewed the chemical properties, pharmacokinetics, clinical application and limitations, mechanism of influencing the biological characteristics of malignant tumors and reshaping the tumor microenvironment, studies of propofol in animal tumor models and its relationship with postoperative prognosis of propofol in combination with the relevant literature in recent years, to lay a foundation for further study on the correlation between propofol and malignant tumor and provide theoretical guidance for the selection of anesthetics in malignant tumor surgery.

ObjectivePeritoneal metastasis is difficult to diagnose using traditional imaging techniques. The main aim of the current study was to develop and validate a nomogram for effectively predicting the risk of peritoneal metastasis in colorectal cancer (PMCC).MethodsA retrospective case-control study was conducted using clinical data from 1284 patients with colorectal cancer who underwent surgery at the First Affiliated Hospital of Guangxi Medical University from January 2010 to December 2015. Least absolute shrinkage and selection operator (LASSO) regression was applied to optimize feature selection of the PMCC risk prediction model and multivariate logistic regression analysis conducted to determine independent risk factors. Using the combined features selected in the LASSO regression model, we constructed a nomogram model and evaluated its predictive value via receiver operating characteristic (ROC) curve analysis. The bootstrap method was employed for repeated sampling for internal verification and the discrimination ability of the prediction models evaluated based on the C-index. The consistency between the predicted and actual results was assessed with the aid of calibration curves.ResultsOverall, 96 cases of PMCC were confirmed via postoperative pathological diagnosis. Logistic regression analysis showed that age, tumor location, perimeter ratio, tumor size, pathological type, tumor invasion depth, CEA level, and gross tumor type were independent risk factors for PMCC. A nomogram composed of these eight factors was subsequently constructed. The calibration curve revealed good consistency between the predicted and actual probability, with a C-index of 0.882. The area under the curve (AUC) of the nomogram prediction model was 0.882 and its 95% confidence interval (CI) was 0.845–0.919. Internal validation yielded a C-index of 0.868.ConclusionWe have successfully constructed a highly sensitive nomogram that should facilitate early diagnosis of PMCC, providing a robust platform for further optimization of clinical management strategies.

BackgroundAuditory neuropathy (AN) is a hearing disorder caused by the failure of inner hair cells, auditory nerve synapses and/or auditory nerves. With the development of high-throughput sequencing technology, the genetic factors of AN have been revealed, and genetic testing has become an important tool for identifying different types of AN.Case descriptionTo study the genetic cause of nonsyndromic auditory neuropathy in a Chinese family. The family was from Henan Province with three affected individuals. The audiological examinations were performed on the affected individuals, and whole-exome sequencing was carried out on the proband. The suspected pathogenic variants screened by the bioinformatic analysis were validated using Sanger sequencing in the family members. We identified three novel variants c.3277G > A (p.Glu1093Lys), c.4024-4G > T, and c.898-2A > G of the OTOF gene in the three children with AN. The first two variants were inherited from their father, and the third variant was inherited from their mother. A minigene assay was designed to test the effect of c.4024-4G > T on splicing. The variants c.3277G > A, c.4024-4G > T, and c.898-2A > G could be classified as likely pathogenic/pathogenic following the ACMG guidelines, and they are considered as the genetic causes for the patients in the family.ConclusionNew pathogenic/likely pathogenic variants of the OTOF gene were identified in a family with AN, enriching the mutational spectrum of the OTOF gene.

Ferroptosis requires not only the accumulation of iron ions, but also changes in many ferroptosis-related regulators, including a decrease in GPX4 and inhibition of SLC7A11 for classical ferroptosis, a deletion of FSP1 or GCH1. Surprisingly, adipose tissue (AT) in the obesity conditions is also accompanied by iron buildup, decreased GSH, and increased ROS. On the neurological side, the pro-inflammatory factor released by AT may have first caused ferroptosis in the vagus nerve by inhibiting of the NRF2-GPX4 pathway, resulting in disorders of the autonomic nervous system. On the immune side, obesity may cause M2 macrophages ferroptosis due to damage to iron-rich ATMs (MFehi) and antioxidant ATMs (Mox), and lead to Treg cells ferroptosis through reductions in NRF2, GPX4, and GCH1 levels. At the same time, the reduction in GPX4 may also trigger the ferroptosis of B1 cells. In addition, some studies have also found the role of GPX4 in neutrophil autophagy, which is also worth pondering whether there is a connection with ferroptosis. In conclusion, this review summarizes the associations between neuroimmune regulation associated with obesity and ferroptosis, and on the basis of this, highlights their potential molecular mechanisms, proposing that ferroptosis in one or more cells in a multicellular tissue changes the fate of that tissue.

Vital signs are important parameters for human health status assessment, and timely, accurate detection is of great significance for modern health care and intelligent medical applications. Detecting vital signs, such as heartbeat and respiration signals, provides a variety of diseases with reliable diagnosis and effective prevention. Conventional contact detection may restrict the behaviors of users, cause additional burdens, and render users uncomfortable. In recent years, noncontact detection technology has successfully achieved remote long-term detection for respiration and heartbeat signals. Compared to conventional contact-detection approaches, noncontact heartbeat and respiration detection using a millimeter-wave radar is preferable as it causes no disturbance to the subject, bringing a comfortable experience, and detects vital signs under natural conditions. However, noncontact vital signs detection is challenging owing to environmental noise. Especially, heartbeat signals are very weak and are merged with respiration harmonics and environmental noise, and their extraction and recognition are even more difficult. This paper applied a frequency-modulated continuous wave (FMCW) radar to detect vital signs. The study also presented a noncontact heartbeat and respiration signals detection approach based on wavelet analysis and autocorrelation computation (WAAC). The millimeter-wave FMCW radar first transmited the electromagnetic signal and received the reflected echo signals from the human body. Thereafter, the phase information of the intermediate frequency signals was extracted, which included respiration and heartbeat signals. The direct current offset of the phase information was corrected, and the phase was unwrapped. Finally, the wavelet packet decomposition was used to reconstruct heartbeat and respiration signals from the original signal, and an autocorrelation computation was utilized to reduce the effect of clutters on the heart rate detection. Experiments were conducted on ten subjects. Results show that the average absolute error percentage of WAAC is less than 1.65% and 1.83% for respiration and heartbeat rates, respectively.

Abstract Background/Aim Lumbar hernia is caused by a defect in the abdominal wall. Due to its rarity, there is no established consensus on optimal treatment for lumbar hernia yet. Thus, we here investigated the clinical, surgical characteristics and outcomes of lumbar hernia by collecting 28 such patients from our hospital. Methods Patients diagnosed with lumbar hernia from our institution between April 2011 and August 2020 were retrospectively collected in this study. Demographics, clinical characteristics and surgical information were recorded. Results A consecutive series of 28 patients with lumbar hernia were retrospectively collected, including 13 males (46%) and 15 females (54%). The ages of the patients ranged from 5 to 79 years (median: 55 years), with a mean age of 55.6 ± 14.9 years. A total of 7 cases had a history of previous lumbar trauma or surgery. There were 11 (39%), 15 (54%) and 2 (7.1%) cases had right, left and bilateral lumbar hernia, respectively. Superior and inferior lumbar hernia were found in 25 (89%) and 3 (11%) patients. General anesthesia was adopted in 16 cases (group A), whereas 12 patients received local anesthesia (group B). Patients in the group B had a shorter hospital stay than that of the group A (3.5 ± 1.3 days vs. 7.1 ± 3.2 days, p = 0.001), as well as total hospitalization expenses between the two groups (2989 ± 1269 dollars vs. 1299 ± 229 dollars, p

Abstract Background Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. Methods Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein–protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518-lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay. Results A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of three DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of seven DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896-TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells. Conclusions We concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis.

Central Asia is a drought-prone region that is sensitive to global climate change. The increased actual evapotranspiration intensifies the drought impacts in this area. However, little is known about the similarities and differences between various types of drought in Central Asia, as well as the relative importance of water income and consumption processes during drought events. Therefore, this study evaluates the trends and characteristics of meteorological, agricultural, and hydrological droughts in Central Asia using precipitation, soil moisture, and terrestrial water storage as indicators; explores the temporal correlation of and spatial similarity between various types of drought; and quantitatively assesses the contribution of water balance variables to drought intensity. The results indicate that drought has intensified in Central Asia, and the trends of precipitation, soil moisture, and terrestrial water storage in this region were −0.75 mm·yr−1 (p = 0.36), −0.0003 m3·m−3 yr−1 (p < 0.01), and −0.3742 cm·yr−1 (p < 0.001), respectively. Severe droughts are typically short in duration and high in intensity. Three various types of drought have low temporal correlation and spatial similarity. Furthermore, agricultural and hydrological droughts were primarily driven by actual evapotranspiration, accounting for relative contributions of 64.38% and 51.04% to these drought types, respectively. Moreover, the extent of increased actual evapotranspiration expanded to cover 49.88% of the region, exacerbating agricultural and hydrological droughts in 23.88% and 35.14% of the total study area, respectively. The study findings demonstrate that actual evapotranspiration plays a critical role in causing droughts. This study establishes a theoretical foundation to carry out drought assessment, the construction of multivariate drought indices, and water resource management in Central Asia.

Swine coronaviruses (CoVs) have been found to cause infection in humans, suggesting that Suiformes might be potential intermediate hosts in CoV transmission from their natural hosts to humans. The present study aims to establish convolutional neural network (CNN) models to predict host adaptation of swine CoVs. Decomposing of each ORF1ab and Spike sequence was performed with dinucleotide composition representation (DCR) and other traits. The relationship between CoVs from different adaptive hosts was analyzed by unsupervised learning, and CNN models based on DCR of ORF1ab and Spike were built to predict the host adaptation of swine CoVs. The rationality of the models was verified with phylogenetic analysis. Unsupervised learning showed that there is a multiple host adaptation of different swine CoVs. According to the adaptation prediction of CNN models, swine acute diarrhea syndrome CoV (SADS-CoV) and porcine epidemic diarrhea virus (PEDV) are adapted to Chiroptera, swine transmissible gastroenteritis virus (TGEV) is adapted to Carnivora, porcine hemagglutinating encephalomyelitis (PHEV) might be adapted to Primate, Rodent, and Lagomorpha, and porcine deltacoronavirus (PDCoV) might be adapted to Chiroptera, Artiodactyla, and Carnivora. In summary, the DCR trait has been confirmed to be representative for the CoV genome, and the DCR-based deep learning model works well to assess the adaptation of swine CoVs to other mammals. Suiformes might be intermediate hosts for human CoVs and other mammalian CoVs. The present study provides a novel approach to assess the risk of adaptation and transmission to humans and other mammals of swine CoVs.

Influenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transcription and translation, yet the underlying mechanisms of virus-induced epigenetic changes from DNA methylation and its role in virus–host interactions remain elusive. Here in this paper, we showed that DNMT1 expression could be suppressed following the inhibition of miR-142-5p or the PI3K/AKT signaling pathway during IAV infection, resulting in demethylation of the promotor region of the 2′-5′-oligoadenylate synthetase-like (OASL) protein and promotion of its expression in A549 cells. OASL expression enhanced RIG-I-mediated interferon induction and then suppressed replication of IAV. Our study elucidated an innate immunity mechanism by which up-regulation of OASL contributes to host antiviral responses via epigenetic modifications in IAV infection, which could provide important insights into the understanding of viral pathogenesis and host antiviral defense.

Compared with water, CO2 has larger expansibility, lower viscosity and lower reaction degree with rock.As an enhanced geothermal system (EGS) seepage heat transfer fluid, CO2 has higher heat transfer efficiency than water.This paper summarizes the research status of fluid/rock interaction in CO2-EGS from three aspects: theoretical research, experimental research and numerical simulation.The changes of reservoir rock properties are evaluated from mineral composition, micro pore structure and mechanical properties.The results show that the main reaction minerals of CO2-water-rock interaction are quartz and feldspar, and the precipitation minerals are montmorillonite, illite and calcite.The interaction of CO2-water-rock will lead to the decline of mechanical properties of reservoir rocks and the change of pore structure characteristics.Finally, the existing problems and development trend of CO2-water-rock interaction in CO2-EGS are discussed, which provides a reference for the development and research of CO2-EGS in the future.

Metro tunnels play a crucial role in urban transportation. However, with growing tunnel operation periods, defects, and large deformations appearing, these are influencing tunnel structural performance and threatening public safety. Three-dimensional (3D) tunnel reconstruction is an effective way to highlight tunnel conditions and provide a basis for engineering management and maintenance. However, the current methods of tunnel 3D reconstruction do not sufficiently combine the qualitative and quantitative characteristics of tunnel states. In this study, a novel method for metro tunnel 3D reconstruction based on structure from motion (SfM) and direct linear transformation (DLT) is proposed. The dimensionless 3D reconstruction point cloud acquired through the SfM method showcases the qualitative characteristics (such as leakage and pipelines) of the tunnel state. The close-range photogrammetry DLT method provides scale information missing from the SfM method and quantitative characteristics (such as profile deformation) of the tunnel state. The SfM-DLT method was tested in a Shanghai metro tunnel, and proved to be feasible and promising for future tunnel inspections.

As a supplement to empirical-statistical methods, physically based methods can be employed to define rainfall thresholds for triggering landslides in areas lacking records of landslides. The transient rainfall infiltration and grid-based regional slope-stability model (TRIGRS), as a physically based model, has been applied to define rainfall thresholds at the basin, slope unit, and grid cell scales. However, as far as we know to date, the influence of soil mechanical and hydraulic parameters on defining rainfall thresholds at various scales has not been comprehensively evaluated. In this study, TRIGRS was used to define rainfall intensity (I) and duration (D) thresholds at various scales for Buzhe village, Pu’an county, Guizhou province, China, under the conditions of different soil physical parameters. The results show that the number of rainfall thresholds decreased with cohesion (c) and internal friction angle (φ) and increased with soil unit weight (γs), excluding the basin scale. Threshold position varied positively with c and φ and negatively with γs. Soil mechanical parameters have a greater influence on the definition of rainfall thresholds based on TRIGRS than hydraulic parameters.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterized by inflammation and destruction of small and medium-sized blood vessels. Clinical disease phenotypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The incidence of AAV has been on the rise in recent years with advances in ANCA testing. The etiology and pathogenesis of AAV are multifactorial and influenced by both genetic and environmental factors, as well as innate and adaptive immune system responses. Multiple case reports have shown that sustained exposure to silica in an occupational environment resulted in a significantly increased risk of ANCA positivity. A meta-analysis involving six case-control studies showed that silica exposure was positively associated with AAV incidence. Additionally, exposure to air pollutants, such as carbon monoxide (CO), is a risk factor for AAV. AAV has seasonal trends. Studies have shown that various environmental factors stimulate the body to activate neutrophils and expose their own antigens, resulting in the release of proteases and neutrophil extracellular traps, which damage vascular endothelial cells. Additionally, the activation of complement replacement pathways may exacerbate vascular inflammation. However, the role of environmental factors in the etiology of AAV remains unclear and has received little attention. In this review, we summarized the recent literature on the study of environmental factors, such as seasons, air pollution, latitude, silica, and microbial infection, in AAV with the aim of exploring the relationship between environmental factors and AAV and possible mechanisms of action to provide a scientific basis for the prevention and treatment of AAV.

The crustal low-velocity zone (LVZ), an important anomaly found in some regional structures of Iceland, is still absent in the Icelandic average velocity structure due to limitations of tomography methods. Using stations from the HOTSPOT experiment and other supplemental stations throughout Iceland, we apply the frequency-Bessel transform method (F-J method) to extract the first two mode dispersion curves from ambient noise data. We obtain an average S-wave velocity (Vs) model of Iceland down to 120 km depth, where two LVZs at depths of 12–22 km and below 55 km are found. The shallow LVZ, whose rationalities are justified using theoretical dispersion curves of certain models to recover themselves, may improve the understanding of the Icelandic average crust. Furthermore, our model shows better representativeness by comparing travel time residuals of the primary wave between observed and synthetic data predicted using different average velocity models. Based on the variations of the Vs gradient, the Icelandic crust with an average thickness of 32 km is divided into the upper crust (0–10 km), middle crust (10–22 km), and lower crust (22–32 km). The asthenosphere starts from the deeper LVZ at 55 km depth, potentially indicating the relatively concentrated melt in this depth range. In this study, crustal LVZs are revealed both in a volcanic active zone and a non-volcanic zone, which may also suggest the LVZ in the average model has more complex origins than the high-temperature zone beneath the central volcanoes. The prevalent thick-cold crustal model of Iceland, considered to rule out the existence of a broad region of partial melt in the crust, also strengthens the possibility of diverse origins. The variations in petrology may also contribute to the crustal LVZ in the average model.

Previous studies find that long noncoding RNA human leukocyte antigen complex P5 (HCP5) is regarded as an oncogene via accelerating cancer cell growth, invasion, metastasis, vascularization, and drug resistance in renal cell carcinoma, gastric cancer, and colorectal cancer. Nevertheless, the effect and regulatory mechanism of HCP5 in laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, HCP5 expression levels were confirmed to be prominently raised in LSCC cell lines. HCP5 knockdown reduced cell proliferation and migration and invasive ability of LSCC cell lines. Furthermore, miR-216a-5p was confirmed to sponge HCP5, and its expression was prominently downregulated in LSCC cell lines and upregulated in HCP5-silenced LSCC cell lines. miR-216a-5p overexpression downregulated the cell proliferation and migration and invasive ability of LSCC cells. Additionally, the protein level of zinc finger E-box binding homeobox 1 (ZEB1), one target gene of miR-216a-5p, was highly expressed in LSCC cell lines, and its expression level was downregulated by HCP5 knockdown and miR-216a-5p overexpression. An miR-216a-5p inhibitor reversed the effect of HCP5 knockdown on the proliferation and migration and invasive ability of LSCC cells. In conclusion, knocking down HCP5 may be a strategy to suppress the malignant biological function via regulating miR-216a-5p/ZEB1. Therefore, HCP5 may become a prospective therapeutic target for LSCC.

Euryale (Euryale ferox Salisb.) is an aquatic crop used as both food and drug in Asia, but its utilization is seriously limited due to low yield. Previously, we hypothesized that Euryale small auxin up RNAs (EuSAURs) regulate seed size, but the underlying biological functions and molecular mechanisms remain unclear. Here, we observed that the hybrid Euryale lines (HL) generate larger seeds with higher indole-3-acetic acid (IAA) concentrations than those in the North Gordon Euryale (WT). Histological analysis suggested that a larger ovary in HL is attributed to longer cells around. Overexpression of EuSAUR62 in rice (Oryza sativa L.) resulted in larger glumes and grains and increased the length of glume cells. Immunofluorescence and protein interaction assays revealed that EuSAUR62 modulates IAA accumulation around the rice ovary by interacting with the rice PIN-FORMED 9, an auxin efflux carrier protein. Euryale basic region/leucine zipper 55 (EubZIP55), which was highly expressed in HL, directly binds to the EuSAUR62 promoter and activated the expression of EuSAUR62. Constant light increased the expression of both EubZIP55 and EuSAUR62 with auxin-mediated hook curvature in HL seedlings. Overall, we proposed that EuSAUR62 is a molecular bridge between light and IAA and plays a crucial role in regulating the size of the Euryale seed.

Apolipoprotein C1 (APOC1) has been found to play an essential part in proliferation and metastasis of numerous cancers, but related mechanism has not been elucidated, especially its function and role in tumor immunity. Through systematic pan-cancer analysis, we identified that APOC1 was closely associated with the infiltration of various immune cells in multiple cancers. Besides, APOC1 was significantly co-expressed with the immune checkpoints, major histocompatibility complex (MHC) molecules, chemokines and other immune-related genes. Furthermore, single-cell sequencing analysis suggested that the vast majority of APOC1 was expressed in macrophages or tumor-associated macrophages (TAMs). Additionally, the expression of APOC1 was significantly related to the prognosis of different cancers. Since APOC1 was most significantly abnormally expressed in renal cell cancer (RCC), subsequent experiments were carried out in RCC to explore the role of APOC1 in tumor immunity. The expression of APOC1 was significantly elevated in the tumor and serum of RCC patients. Besides, APOC1 was mainly expressed in the macrophage and it was closely related to the immune cell infiltration of RCC. Co-culture with RCC cells could induce the generation of TAMs with M2 phenotype which be blocked by silencing APOC1. The expression of APOC1 was elevated in the M2 or TAMs and APOC1 promoted M2 polarization of macrophages through interacting with CD163 and CD206. Furthermore, macrophages overexpressing APOC1 promoted the metastasis of RCC cells via secreting CCL5. Together, these data indicate that APOC1 is an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis.

Colorectal cancer (CRC) is one of the most common malignant tumors with a high incidence rate and mortality. LncRNA is an important regulator of the immune system. It is of great significance to study immune-related lncRNAs (IR-lncRNAs) for CRC. In this study, we screened IR-lncRNAs differentially expressed in normal and CRC tissues, and Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator were applied to construct IR-lncRNA prognostic signature in TCGA training dataset, and its predictive capability for the prognosis of CRC patients was verified in GSE39582 validation dataset. The novel signature was identified as an independent predictor of prognosis in CRC patients. In addition, the signature could accurately predict the feature of the immune microenvironment and therapeutic response in CRC patients. The CMap database was adopted to screen for small molecule candidate drugs that can reverse and treat high-risk CRC patients. Finally, the expression of six IR-lncRNAs were verified by qRT-PCR in clinical specimens from our patient cohort. In conclusion, we construct an IR-lncRNA prognostic signature, which is a powerful biomarker of CRC and can accurately predict the prognosis, immune microenvironment feature, and therapeutic response of CRC patients.

The roots of Angelica sinensis (Oliv.) Diels are well known for their efficacy in promoting blood circulation. Although many studies have indicated that phthalides are the main chemical components responsible for the pharmacological properties of A. sinensis, the phthalide biosynthetic pathway and enzymes that transform different phthalides are still poorly understood. We identified 108 potential candidate isoforms for phthalide accumulation using transcriptome and metabolite profile analyses. Then, six enzymes, including phospho-2-dehydro-3-deoxyheptonate aldolase 2, shikimate dehydrogenase, primary amine oxidase, polyphenol oxidase, tyrosine decarboxylase, and shikimate O-hydroxycinnamoyl transferase, were identified and proven to be involved in phthalide accumulation by heterologously expressing these proteins in Escherichia coli. We proposed a possible mechanism underlying phthalide transformation and biosynthetic pathways in A. sinensis based on our findings. The results of our study can provide valuable information for understanding the mechanisms underlying phthalide accumulation and transformation and enable further development of quality control during the cultivation of A. sinensis.