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tRNA-derived small RNAs (tsRNAs) are a novel class of small noncoding RNAs, precisely cleaved from tRNA, functioning as regulatory molecules. The topic of tsRNAs in injuries has not been extensively discussed, and studies on tsRNAs are entering a new era. Here, we provide a fresh perspective on this topic. We systematically reviewed the classification, generation, and biological functions of tsRNAs in response to stress, as well as their potential as biomarkers and therapeutic targets in various injuries, including lung injury, liver injury, renal injury, cardiac injury, neuronal injury, vascular injury, skeletal muscle injury, and skin injury. We also provided a fresh perspective on the association between stress-induced tsRNAs and organ injury from a clinical perspective.

Extant ecdysozoans (moulting animals) are represented by a great variety of soft-bodied or articulated organisms that may or may not have appendages. However, controversies remain about the vermiform nature (i.e. elongated and tubular) of their ancestral body plan. We describe here Beretella spinosa gen. et sp. nov. a tiny (maximal length 3 mm) ecdysozoan from the lowermost Cambrian, Yanjiahe Formation, South China, characterized by an unusual sack-like appearance, single opening, and spiny ornament. Beretella spinosa gen. et sp. nov has no equivalent among animals, except Saccorhytus coronarius, also from the basal Cambrian. Phylogenetic analyses resolve both fossil species as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early off-shot along the stem-line Ecdysozoa. Although it became extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature of the earliest representatives of the group.

Abstract Background Periodontitis is a chronic oral inflammatory disease that seriously affects people's quality of life. The purpose of our study was to investigate the correlation between the systemic immune inflammation index (SII) and periodontitis by utilizing a large national survey. This will establish a reference for the early identification and management of periodontitis. Methods This study comprised the adult US population who participated in a national periodontitis surveillance project during the six years from 2009 to 2014. Through the utilization of univariate and multivariate weighted logistic regression, we investigated the correlation between the systemic immune inflammation index and periodontitis. Additionally, we employed sensitivity analyses to evaluate the robustness of our findings. Results The study involved 10,366 participants with an average age of 51.00 years, of whom 49.45% were male (N = 5126) and 50.55% were female (N = 5240). The prevalence of periodontitis is estimated to be about 38.43% in the US adults aged 30 or older population. Our logistic regression models indicated a positive association between a SII higher than 978 × 109/L and periodontitis. The elder group (aged 50 or older) with SII higher than 978 × 109/L demonstrated a significant correlation with periodontitis in the fully adjusted model (Odds Ratio [OR] = 1.409, 95% Confidence Interval [CI] 1.037, 1.915, P = 0.022). However, there is no statistical difference among adults aged 30 to 50. The robustness of our findings was confirmed through sensitivity analyses. Conclusions Our study highlights that SII is associated with periodontitis in a nationally representative sample of US adults. And the SII is significantly associated with a high risk of periodontitis in individuals aged 50 or older.

Biosensing platforms have become increasingly important in our daily lives due to their ability to provide real-time monitoring with low cost, high sensitivity, and specificity. Carbon nanotubes possess unique optical, electrical, and physical/chemical characteristics that can significantly enhance the electron transfer rate in biosensors, thereby improving sensing performance and enabling rapid detection of biochemical molecules and electrophysiological signals. Additionally, carbon nanotubes facilitate high-resolution imaging detection of cells and tissues. The bio-nano platform based on carbon nanotubes holds excellent potential for integrating diagnosis and treatment to achieve precision medicine goals. As a result, carbon nanotube-based biosensors are emerging as the most promising candidate for medical diagnostics. This paper reviews the synthesis of carbon nanotubes, their application in sensors for medical diagnosis, and their potential use in remediation therapy. Furthermore, it explores the existing limitations and future development trends of carbon nanotubes in the medical field. This interdisciplinary research offers abundant opportunities for researchers interested in carbon nanotube synthesis, medical diagnostics, and regenerative therapy.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic disease with an unclear etiology and no effective treatment. This study aims to elucidate the pathogenic mechanism networks involving multiple targets and pathways in IPF. Extracts and metabolites of Astragalus membranaceus (AM) and Radix paeoniae rubra (RPR), two well-known traditional Chinese medicines, have demonstrated therapeutic effects on IPF. However, the underlying mechanisms of AM and RPR remain unclear. Utilizing network pharmacology analysis, differentially expressed genes (DEGs) associated with IPF were obtained from the GEO database. Targets of AM and RPR were identified using the TCM Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction. A protein–protein interaction (PPI) network was subsequently constructed and analyzed using the STRING database and Cytoscape software. Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes analysis were conducted using Metascape. Additionally, a component-target-pathway network and a Sankey diagram were employed to identify the main active components, and molecular docking was performed between these components and proteins encoded by key targets. Finally, in vivo studies were conducted based on network pharmacology. A total of 117 common targets between DEGs of IPF and drug targets were identified and included in the PPI network, in which AKT1, MAPK3, HSP90AA1, VEGFA, CASP3, JUN, HIF1A, CCND1, PTGS2, and MDM2 were predicted as key targets. These 117 targets were enriched in the PI3K-AKT pathway, HIF-1 signaling pathway, apoptosis, and microRNAs in cancer. Astragaloside III, (R)-Isomucronulatol, Astragaloside I, Paeoniflorin, and β-sitosterol were selected as the main active components. Docking scores ranged from − 4.7 to − 10.7 kcal/mol, indicating a strong binding affinity between the main active compounds and key targets. In vivo studies have indeed shown that AM and RPR can alleviate the pathological lung fibrotic damage caused by bleomycin treatment. The treatment with AM and RPR resulted in a reduction of mRNA levels for key targets AKT1, HSP90AA1, CASP3, MAPK3, and VEGFA. Additionally, the protein expression levels of AKT1, HSP90AA1, and VEGFA were also reduced. These results support the therapeutic potential of AM and RPR in ameliorating pulmonary fibrosis and provide insight into the molecular mechanisms involved in their therapeutic effects.

To solve the problem that noise seriously affects the online monitoring of parts signals of outdoor machinery, this paper proposes a signal reconstruction method integrating deep neural network and compression sensing, called ADMM-1DNet, and gives a detailed online vibration signal monitoring scheme. The basic approach of the ADMM-1DNet network is to map the update steps of the classical Alternating Direction Method of Multipliers (ADMM) into the deep network architecture with a fixed number of layers, and each phase corresponds to an iteration in the traditional ADMM. At the same time, what differs from other unfolded networks is that ADMM-1DNet learns a redundant analysis operator, which can reduce the impact of outdoor high noise on reconstruction error by improving the signal sparse level. The implementation scheme includes the field operation of mechanical equipment and the operation of the data center. The empirical network trained by the local data center conducts an online reconstruction of the received outdoor vibration signal data. Experiments are conducted on two open-source bearing datasets, which verify that the proposed method outperforms the baseline method in terms of reconstruction accuracy and feature preservation, and the proposed implementation scheme can be adapted to the needs of different types of vibration signal reconstruction tasks.

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes.Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates.Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)–mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028–1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094–4.516). Both analyses yielded no consistent evidence of other associations.Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.

For solving the dilemma of the short exothermic life-span of WO3 based metastable interstitial composites (MICs) with extensive application prospect, this paper has firstly designed the promising anti-wetting Al/WO3 MICs via electrophoresis assembly of nano-Al and WO3 particles fabricated by hydrothermal synthesis method, followed by the subsequent fluorination treatment. A combination of X ray diffraction (XRD), field emission scanning electron microscope (FESEM), energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FT-IR) techniques were utilized in order to characterize the crystal structure, microstructure, and elemental composition distribution of target films after different natural exposure tests. The product with uniform distribution and high purity possesses a high contact angle of ∼170° and a minute sliding angle of ∼1°, and displays the outstanding anti-wetting property using droplets with different surface tensions. It also shows great moisture stability in high relative-humidity circumstances after one year of the natural exposure experiment. Notably, the heat output of a fresh sample can reach up to 2.3 kJ/g and retain 96% after the whole exposure test, showing outstanding thermo-stability for at least one year. This work further proposed the mechanism of anti-wetting Al/WO3 MICs considering the variation tendency of their DSC curve, providing a valuable theoretical reference for designing other self-protected MICs with a long exothermic life-span applied in wide fields of national defense, military industry, etc.

Abstract To improve the reliability and reduce the maintenance cost of transformer oil, a life prediction of transformer oil is needed so that the maintenance of transformer can be performed correctly. However, it is difficult to predict the reliable lifetime of transformer oil accurately because of its unkind operating condition at different environments. To solve this problem, based on the theory of accelerated life testing (ALT), a reliability assessment method for transformer insulating oil on a normal operational conditions is proposed. An inverse power Weibull distribution model for insulating oil lifetime with voltage is built. Numerical procedure of model parameter estimation is presented, the variances of model parameters and reliability indices, which including mean lifetime, reliability, reliable lifetime at given reliability and failure rate, are derived. The feasibility and correctness of the proposed method are validated by real lifetime data of transformer insulating oil in literature. The reliability of transformer insulating oil used at normal usage conditions are predicted by the proposed method, and the point and interval estimations of reliability indices are evaluated. The results show that reliable lifetime and mean lifetime under reliability limit should be considered simultaneously in repair or replacement of transformer insulating oil.

IntroductionTendinopathy, the most common form of chronic tendon disorder, leads to persistent tendon pain and loss of function. Profiling the heterogeneous cellular composition in the tendon microenvironment helps to elucidate rational molecular mechanisms of tendinopathy.Methods and resultsIn this study, through a multi-modal analysis, a single-cell RNA- and ATAC-seq integrated tendinopathy landscape was generated for the first time. We found that a specific cell subpopulation with low PRDX2 expression exhibited a higher level of inflammation, lower proliferation and migration ability, which not only promoted tendon injury but also led to microenvironment deterioration. Mechanistically, a motif enrichment analysis of chromatin accessibility showed that FOXO1 was an upstream regulator of PRDX2 transcription, and we confirmed that functional blockade of FOXO1 activity induced PRDX2 silencing. The TNF signaling pathway was significantly activated in the PRDX2-low group, and TNF inhibition effectively restored diseased cell degradation.DiscussionWe revealed an essential role of diseased cells in tendinopathy and proposed the FOXO1-PRDX2-TNF axis is a potential regulatory mechanism for the treatment of tendinopathy.

Background: Herb pair of Astragali Radix (AR) and Spreading Hedyotis Herb (SH) has been frequently prescribed in clinical for the treatment of lung cancer owing to its favorable efficacy. Yet, the mechanism under the therapeutic effects remained unveiled, which has limited its clinical applications, and new drug development for lung cancer.Methods: The bioactive ingredients of AR and SH were retrieved from the Traditional Chinese Medicine System Pharmacology Database, with the targets of obtained components predicted by Swiss Target Prediction. Genes related to lung adenocarcinoma (LUAD) were acquired from GeneCards, OMIM and CTD databases, with the hub genes of LUAD screened by CTD database. The intersected targets of LUAD and AR-SH were obtained by Venn, with David Database employed to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Survival analysis of the hub genes of LUAD was carried out using TCGA-LUAD dataset. Molecular docking of core proteins and active ingredients was performed by Auto-Dock Vina software, followed by molecular dynamics simulations of protein-ligand complexes with well-docked conformations.Results: 29 active ingredients were screened out with 422 corresponding targets predicted. It is revealed that AR-SH can act on various targets such as EGFR, MAPK1, and KARS by ursolic acid (UA), Astragaloside IV(ASIV), and Isomucronulatol 7,2′-di-O-glucoside (IDOG) to alleviate the symptoms of LUAD. Biological processes involved are protein phosphorylation, negative regulation of apoptotic process, and pathways involved are endocrine resistance, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt, and HIF-1 pathway. Molecular docking analysis indicated that the binding energy of most of the screened active ingredients to proteins encoded by core genes was less than −5.6 kcal/mol, with some active ingredients showing even lower binding energy to EGFR than Gefitinib. Three ligand-receptor complexes including EGFR-UA, MAPK1-ASIV, and KRAS-IDOG were found to bind relatively stable by molecular dynamics simulation, which was consistent with the results of molecule docking.Conclusion: We suggested that the herb pair of AR-SH can act on targets like EGFR, MAPK1 and KRAS by UA, ASIV and IDOG, to play a vital role in the treatment and the enhancement of prognosis of LUAD.

Coalbed Methane (CBM) is an unconventional form of natural gas which is self-generated and self-stored in coal seams. In order to realize the effective exploitation of CBM in Zhengzhuang block, microstructure, wettability, permeability, rock mechanics and in-situ stress of coal were studied in this research. It is found that high rank anthracite characterized by high vitrinite content and low inorganic mineral content, is abundant in CBM. More than 96% of inorganic minerals are clays dominated by kaolinite and illite. Various types of pores are developed on the coal. The wettability of coal differs from high to low to surface water, active water, and foam fracturing fluid; and contact angles of coal with active water and foam fracturing fluid decrease with the increase of burial depth. Gradients of fracture pressure and closure pressure in No.3 coal seam are higher than that of No.15 coal seam. The elastic modulus of coal is lower than that of sandstone. The construction curve of hydraulic fracturing shows that, when the construction flow rate and sand quantity are similar, the construction pressure of prepad in No.3 coal seam is lower than the pumping pressure of No.15 coal seam, but the propagated pressure is higher than that of No.15 coal seam. The drainage effect of No.3 coal seam with large pore volume, shallow burial depth and obvious fracture pressure is better than that of No.15 coal seam. The comprehensive understanding of coal physical properties and engineering practice in the block provide certain guiding significance to the CBM exploitation in Qinshui Basin.

Anabarella, a conspicuous taxon of early mollusc, is widely distributed in the early Cambrian strata and is considered an important link in the evolutionary lineage that reflects a transitional form from helcionelloids to bivalves. In South China, Anabarella has mainly been documented from Yunnan, Shaanxi, Sichuan, and Hubei provinces. However, the taxonomy of Anabarella is questionable, which has implications for the interpretation of the genus’ temporal and spatial distribution. New and abundant well-preserved specimens of the helcionelloid mollusc Anabarella were recovered from the Member 5 of the Yanjiahe Formation in the Three Gorges area. Through morphological study, these specimens can be definitely identified as A. plana. On the basis of this new material, the species of Anabarella previously reported in the literature from South China were taxonomically revised, and, with the exception of A. plana from the Yanjiahe Formation, other species should be assigned to Igorella. Therefore, at present, A. plana is the only valid species of the genus Anabarella in South China and is limited to Cambrian Stage 2. Study of the available specimens of A. plana reveal three types of microstructures: convex polygonal impressions, concave polygons, and lamello-fibrillar microstructure. In addition, the thicker shell of the sub-apical area and the three different structures of the sub-apical area provide more evidence that A. plana might have adapted a semi-infanual mode of life and indicate that Anabarella is a likely ancestor of Watsonella.

Hexangulaconulariids, a family of biradially symmetrical medusozoan cnidarians, have been widely reported from the Lower Cambrian of South China. The four currently recognized genera of hexangulaconulariids differ from each other mainly in the number of faces in the abapical region of the periderm. However, previously published illustrations of the monospecific type genus, Hexangulaconularia, clearly show two distinct morphotypes, one with six faces and the other with 10. Specimens with 10 faces are herein reassigned to the genus Decimoconularia. In addition, the new species D. anisfacialis is described from the Kuanchuanpu Formation (Cambrian Fortunian Stage) in the Kuanchuanpu and Shizhonggou sections in Ningqiang County, southern Shaanxi Province, China. Also described are additional specimens of H. formosa from the same formation in the Zhangjiagou section in Xixiang County, southern Shaanxi Province, and from Member 2 of the Yanjiahe Formation (Cambrian Fortunian Stage) in western Hubei Province. The discovery of D. anisfacialis extends the known stratigraphical range of Decimoconularia, now composed of two species, downward from Cambrian Stage 2 into the Fortunian Stage. Additionally, certain specimens previously assigned to H. formosa are reassigned to D. anisfacialis. The diagnoses of Hexangulaconularia, Decimoconularia, and Hexangulaconulariidae are emended accordingly. In accordance with the rule of time priority, the previously designated type genus and species, Hexaconularia He and Yang, 1986 and Hexaconularia sichuanensis He and Yang, 1986, are replaced herein by Hexangulaconularia He, in Xing et al., 1983.

IntroductionEsophageal squamous cell carcinoma (ESCC) is one of the most common cancers globally, with significant cell heterogeneity and poor prognosis. Distant metastasis in ESCC is one of the key factors that affects the prognosis of patients.Methods and resultsStarting with the analysis of ESCC single-cell sequencing data, we constructed a single-cell atlas of ESCC in detail and clarified the cell heterogeneity within tumor tissues. Through analysis of epithelial-mesenchymal transition (EMT) levels, gene expression, and pathway activation, we revealed the existence of a novel subpopulation of SAA1+ malignant cells in ESCC that are highly aggressive and closely associated with distant metastasis of ESCC. In vitro wound healing and transwell assays confirmed a strong invasion capacity of ESCC tumor cells with high expression of SAA1. Then, we constructed an effective and reliable prediction model based on the gene expression pattern of SAA1+ malignant cell subpopulations and confirmed that patients in the high-risk group had significantly worse prognosis than those in the low-risk group in the training cohort, internal verification cohort and external verification cohort.DiscussionThis manuscript contributes to exploration of the heterogeneity of ESCC tumor tissues and the search for new ESCC subpopulations with special biological functions. These results contribute to our understanding of the underlying mechanisms of distant metastasis of ESCC and thus provide a theoretical basis for improved therapies.

Jinwu Gutong capsule (JGC) is a traditional Chinese medicine formula for the treatment of osteoarthritis (OA). Synovitis is a typical pathological change in OA and promotes disease progression. Elucidating the therapeutic mechanism of JGC is crucial for the precise treatment of OA synovitis. In this study, we demonstrate that JGC effectively inhibits hyperproliferation, attenuates inflammation, and promotes apoptosis of synovial cells. Through scRNA-seq data analysis of OA synovitis, we dissected two distinct cell fates that influence disease progression (one fate led to recovery while the other fate resulted in deterioration), which illustrates the principles of fate determination. By intersecting JGC targets with synovitis hub genes and then mimicking picomolar affinity interactions between bioactive compounds and binding pockets, we found that the quercetin-AKR1C3 pair exhibited the best affinity, indicating that this pair constitutes the most promising molecular mechanism. In vitro experiments confirmed that the expression of AKR1C3 in synovial cells was reduced after JGC addition. Further overexpression of AKR1C3 significantly attenuated the therapeutic efficacy of JGC. Thus, we revealed that JGC effectively treats OA synovitis by inhibiting AKR1C3 expression.

Recent studies have revealed that the effect of intestinal microecological disorders on organismal physiology is not limited to the digestive system, which provides new perspectives for microecological studies and new ideas for clinical diagnosis and prevention of microecology-related diseases. Stress triggers impairment of intestinal mucosal barrier function, which could be duplicated by animal models. In this paper, pathological animal models with high prevalence and typical stressors—corresponding to three major stressors of external environmental factors, internal environmental factors, and social psychological factors, respectively exemplified by burns, intestinal ischemia-reperfusion injury (IIRI), and depression models—were selected. We summarized the construction and evaluation of these typical animal models and the effects of stress on the organism and intestinal barrier, as well as systematically discussed the effects of different stresses on the intestinal mucosal barrier and intestinal microecology.

Abstract Image registration-based local displacement analysis enables evaluation of respiratory motion between two computed tomography-captured lung volumes. The objective of this study was to compare diaphragm movement among emphysema, idiopathic pulmonary fibrosis (IPF) and normal subjects. 29 normal, 50 emphysema, and 51 IPF subjects were included. A mass preserving image registration technique was used to compute displacement vectors of local lung regions at an acinar scale. Movement of the diaphragm was assumed to be equivalent to movement of the basal lung within 5 mm from the diaphragm. Magnitudes and directions of displacement vectors were compared between the groups. Three-dimensional (3D) and apico-basal displacements were smaller in emphysema than normal subjects (P = 0.003, P = 0.002). Low lung attenuation area on expiration scan showed significant correlations with decreased 3D and apico-basal displacements (r = − 0.546, P

Atherosclerosis (AS) is a chronic inflammatory disease of large- and medium-sized arteries that causes ischemic heart disease, strokes, and peripheral vascular disease, collectively called cardiovascular disease (CVD), and is the leading cause of CVD resulting in a high rate of mortality in the population. AS is pathological by plaque development, which is caused by lipid infiltration in the vessel wall, endothelial dysfunction, and chronic low-grade inflammation. Recently, more and more scholars have paid attention to the importance of intestinal microecological disorders in the occurrence and development of AS. Intestinal G-bacterial cell wall lipopolysaccharide (LPS) and bacterial metabolites, such as oxidized trimethylamine (TMAO) and short-chain fatty acids (SCFAs), are involved in the development of AS by affecting the inflammatory response, lipid metabolism, and blood pressure regulation of the body. Additionally, intestinal microecology promotes the progression of AS by interfering with the normal bile acid metabolism of the body. In this review, we summarize the research on the correlation between maintaining a dynamic balance of intestinal microecology and AS, which may be potentially helpful for the treatment of AS.

Abstract The purpose of this study was to develop a fully-automated segmentation algorithm, robust to various density enhancing lung abnormalities, to facilitate rapid quantitative analysis of computed tomography images. A polymorphic training approach is proposed, in which both specifically labeled left and right lungs of humans with COPD, and nonspecifically labeled lungs of animals with acute lung injury, were incorporated into training a single neural network. The resulting network is intended for predicting left and right lung regions in humans with or without diffuse opacification and consolidation. Performance of the proposed lung segmentation algorithm was extensively evaluated on CT scans of subjects with COPD, confirmed COVID-19, lung cancer, and IPF, despite no labeled training data of the latter three diseases. Lobar segmentations were obtained using the left and right lung segmentation as input to the LobeNet algorithm. Regional lobar analysis was performed using hierarchical clustering to identify radiographic subtypes of COVID-19. The proposed lung segmentation algorithm was quantitatively evaluated using semi-automated and manually-corrected segmentations in 87 COVID-19 CT images, achieving an average symmetric surface distance of $$0.495\pm 0.309$$ 0.495 ± 0.309 mm and Dice coefficient of $$0.985\pm 0.011$$ 0.985 ± 0.011 . Hierarchical clustering identified four radiographical phenotypes of COVID-19 based on lobar fractions of consolidated and poorly aerated tissue. Lower left and lower right lobes were consistently more afflicted with poor aeration and consolidation. However, the most severe cases demonstrated involvement of all lobes. The polymorphic training approach was able to accurately segment COVID-19 cases with diffuse consolidation without requiring COVID-19 cases for training.

Osteosarcoma is the most common malignant bone tumor in adolescents, and metastasis is the key reason for treatment failure and poor prognosis. Once metastasis occurs, the 5-year survival rate is only approximately 20%, and assessing and predicting the risk of osteosarcoma metastasis are still difficult tasks. In this study, cellular communication between tumor cells and nontumor cells was identified through comprehensive analysis of osteosarcoma single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, illustrating the complex regulatory network in the osteosarcoma microenvironment. In line with the heterogeneity of osteosarcoma, we found subpopulations of osteosarcoma cells that highly expressed COL6A1, COL6A3 and MIF and were closely associated with lung metastasis. Then, BCDEG, a reliable risk regression model that could accurately assess the metastasis risk and prognosis of patients, was established, providing a new strategy for the diagnosis and treatment of osteosarcoma.

Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause and risk factor for chronic obstructive pulmonary disease, but the field lacks a large-animal model that allows for longitudinal assessment of pulmonary function. We hypothesized that ferrets would model human AATD-related lung and hepatic disease. AAT-knockout (AAT-KO) and PiZZ (E342K, the most common mutation in humans) ferrets were generated and compared with matched controls using custom-designed flexiVent modules to perform pulmonary function tests, quantitative computed tomography (QCT), bronchoalveolar lavage (BAL) proteomics, and alveolar morphometry. Complete loss of AAT (AAT-KO) led to increased pulmonary compliance and expiratory airflow limitation, consistent with obstructive lung disease. QCT and morphometry confirmed emphysema and airspace enlargement, respectively. Pathway analysis of BAL proteomics data revealed inflammatory lung disease and impaired cellular migration. The PiZ mutation resulted in altered AAT protein folding in the liver, hepatic injury, and reduced plasma concentrations of AAT, and PiZZ ferrets developed obstructive lung disease. In summary, AAT-KO and PiZZ ferrets model the progressive obstructive pulmonary disease seen in AAT-deficient patients and may serve as a platform for preclinical testing of therapeutics including gene therapy.

Seasonal influenza A (H3N2) virus has been a concern since its first introduction in humans in 1968. Accumulating antigenic changes in viral hemagglutinin (HA), particularly recent cocirculations of multiple HA genetic clades, allow H3N2 virus evade into humans annually. From 2010, the binding of neuraminidase (NA) to sialic acid made the traditional assay for HA inhibition antibodies (Abs) unsuitable for antigenicity characterization. Here, we investigated the serum anti-NA response in a cohort with a seroconversion of microneutralizing (MN) Abs targeting the circulating strain, A/Singapore/INFIMH-16-0019/2016 (H3N2, 3C.2a1)-like, a virus during 2018/2019 flu seasons. We discovered that MN Ab titers show no difference between children and adults. Nevertheless, higher titers of Abs with NA activity inhibition (NI) activity of 129 and seroconversion rate of 68.42% are presented in children aged 7–17 years (n = 19) and 73.47 and 41.17% in adults aged 21–59 years (n = 17), respectively. The MN Abs generated in children display direct correlations with HA- and NA-binding Abs or NI Abs. The NI activity exhibited cross-reactivity to N2 of H3N2 viruses of 2007 and 2013, commonly with 329-N-glycosylation and E344 in N2, a characteristic of earlier 3C.2a H3N2 virus in 2014. The percentage of such viruses pronouncedly decreased and was even replaced by those dominant H3N2 viruses with E344K and 329 non-glycosylation, which have a significantly low activity to the tested antisera. Our findings suggest that NI assay is a testable assay applied in H3N2 infection in children, and the antigenic drift of current N2 should be considered for vaccine selection.

ABSTRACTInterferon-induced transmembrane protein 3 (IFITM3) as an antiviral factor can inhibit replication of several viruses including influenza virus. A single-nucleotide polymorphism rs12252-C of IFITM3 results in a truncated IFITM3 protein lacking its first 21 amino acids, which is much higher in the Han Chinese population and associated with severe illness in adults infected with pandemic influenza H1N1/09 virus. To investigate if IFITM3 or IFITM3 rs12252-C could affect the antibody response after influenza vaccination, we detected the haemagglutination inhibition (HI) of 171 healthy young adult volunteers (IFITM3 rs12252-C/C, C/T, T/T carriers) and in an IFITM3-deletion mouse model (Ifitm3-/-) after trivalent inactivated vaccine (TIV) immunization. Seroconversion rates for H1N1, H3N2 and B viruses in IFITM3 rs12252-C/C genotype carriers was lower compared with C/T and T/T donors. Significantly lower levels of specific antibodies to H1N1, H3N2 and B viruses and total IgG were observed in Ifitm3-/- mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, TIV-specific IgG+ antibody secreting cells and T follicular helper cells in Ifitm3-/- mice were lower compared with wild type mice. However, the number of memory B cells was higher in Ifitm3-/- mice at day 7 after booster. The HI level of Ifitm3-/- mice remained lower than WT mice after third vaccination. Moreover, the transcriptional network regulating GC B cell and plasma cell differentiation was abnormal in Ifitm3-/- mice. Our results indicate that IFITM3 deletion attenuated the antibody response. The mechanism of influenza-IFITM3 interactions affecting the antibody response requires further investigation.

Abstract This paper addresses issues with monitoring systems that identify and track illegal drones. The development of drone technologies promotes the widespread commercial application of drones. However, the ability of a drone to carry explosives and other destructive materials may pose serious threats to public safety. In order to reduce these threats, we propose an acoustic-based scheme for positioning and tracking of illegal drones. Our proposed scheme has three main focal points. First, we scan the sky with switched beamforming to find sound sources and record the sounds using a microphone array; second, we perform classification with a hidden Markov model (HMM) in order to know whether the sound is a drone or something else. Finally, if the sound source is a drone, we use its recorded sound as a reference signal for tracking based on adaptive beamforming. Simulations are conducted under both ideal conditions (without background noise and interference sounds) and non-ideal conditions (with background noise and interference sounds), and we evaluate the performance when tracking illegal drones.

Feature extraction is the key technology in the data-driven intelligent fault diagnosis methods of rolling bearing. However, the acquired features by the traditional methods, which mainly based on time-frequency domain, sometimes cannot well represent the characteristics of the signal and are difficult to accurately identify because of their complexity and subjectivity. Aiming at this problem, the sparse representation theory is used to the field of fault diagnosis because the different types of rolling bearing fault signals only has the highest matching degree with the dictionary atoms trained by the same type of fault signals. A novel method based on the double sparse dictionary model joint with Deep Belief Network (DBN) is proposed for the fault diagnosis of rolling bearing. Firstly, each type of fault signal is trained according to the double sparse dictionary learning algorithm and the corresponding double sparse subdictionaries is obtained. In order to reduce the feature dimension of sparse representation coefficients, the low contribution atoms of all subdictionaries are removed and the rest are recombined into a comprehensive double sparse dictionary. Then, the Orthogonal Matching Pursuit (OMP) algorithm is adopted to obtain the corresponding sparse feature coefficients of each fault signal on the comprehensive double sparse dictionary. Finally, the coefficient is used as the input of DBN to train and judge the faults of the rolling bearing. The experimental results show that the proposed method has higher diagnosis accuracy and stability compared with the traditional intelligent fault diagnosis methods, and the training and testing time of DBN is greatly reduced.

To explore the applicability of the carbon isotope composition (δ13C) of fossil charcoal for the quantitative reconstruction of paleoclimates, we selected five points in Shaanxi province, from north to south, to collect modern Pinus species and Quercus species to sample covering areas with obvious climatic differences. In order to reveal the relationships between δ13C of charcoal and climate variables on the basis of carbonization experiments, we evaluated the fractionation mechanism of δ13C of charcoal, and compared the differences between δ13C of charcoal in wildfire experiments and indoor experiments regarding genera and species. The results showed significant differences in δ13C between genera but no significant differences among species. Additionally, the δ13C of charcoal was significantly negatively correlated with precipitation and positively correlated with evaporation, which could be determined from δ13C values in the study area to reconstruct ancient precipitation and evaporation in the future.

Some small shelly fossils are important index fossils for global stratigraphic subdivisions and correlations of the Cambrian Terreneuvian. The first appearance datum (FAD) of the cosmopolitan mollusk Aldanella attleborensis has been suggested as one of the potential markers for defining the base of Cambrian Stage 2. Aldanella fossils were uncommon in South China, and if occurring, were often described as Aldanella yanjiaheensis, A. attleborensis, or indeterminate species in the literature, while A. yanjiaheensis was often taken as a junior synonym of A. attleborensis. Nevertheless, a detailed taxonomic revision of A. yanjiaheensis based on material from its type locality awaits to be made. In this study, we systematically re-evaluated A. yanjiaheensis based on the numerous specimens collected from the base of Member 5 of the Yanjiahe Formation in the Three Gorges area, western Hubei Province of South China. Detailed taxonomic comparison further substantiates that A. yanjiaheensis is a junior synonym of A. attleborensis, signifying its strong potential for a global correlation across paleocontinents. Morphological parameter analyses indicate that the length and width of shell tube of A. attleborensis shows allometric growth. The nearly cosmopolitan distribution and characteristic morphology of A. attleborensis indicate that it can play a significant role in the subdivision and correlation of Cambrian Stage 2. The co-occurrence of A. attleborensis and Watsonella crosbyi from the base of Member 5 of the Yanjiahe Formation corroborates that Member 5 belongs to Cambrian Stage 2.

Oral squamous cell carcinoma (OSCC), a kind of malignant cancer, is associated with increasing morbidity and mortality. Patients with different genetic ancestries may respond differently to clinical treatment. The limited understanding of the influence of genetic ancestry and genetic characteristics on OSCC impedes the development of precision medicine. To provide a reference for clinical treatment, this study comprehensively analyzed multigenomic differences in OSCC patients with different genetic ancestries and their impact on prognosis. An analysis of data from OSCC patients with different genetic ancestries in The Cancer Genome Atlas (TCGA) showed that the overall survival (OS) of African (AFR) patients was lower than that of primarily European (EUR) patients, and differences were also observed in the tumor–stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs), which are associated with prognosis. FAT1 is a key mutant gene in OSCC, and it has inconsistent effects on clinical evolution for patients with diverse genetic characteristics. PIKfyve and CAPN9 showed a significant difference in mutation frequency between EUR and AFR; PIKfyve was related to Ki-67 expression, suggesting that it could promote tumor proliferation, and CAPN9 was related to the expression of Bcl-2, promoting tumor cell apoptosis. A variant methylation locus, cg20469139, was correlated with the levels of PD-L1 and Caspase-7 and modulated tumor cell apoptosis. A novel ceRNA model was constructed based on genetic ancestries, and it could accurately evaluate patient prognosis. More importantly, although T cell dysfunction scores could determine the potential of tumor immune escape, the efficacy was obviously affected by patients’ genetic ancestries. To provide patients with more precise, personalized therapy and to further improve their quality of life and 5-year survival rate, the influence of genetic ancestry should be fully considered when selecting treatments.

The isolated sclerites of the Ocruranus and Eohalobia group are abundant among the early Cambrian small shelly fossil assemblages, which were recently assigned to the same scleritome as an early member of the polyplacophoran (chiton) stem lineage. However, the scleritome reconstruction and zoological affinities of these sclerites are still controversial due to the lack of exceptionally preserved articulated specimens with in-situ sclerites. Herein, we report new specimens of Ocruranus and Eohalobia sclerites from Member 5 of the Yanjiahe Formation, which provide new insights into the reconstruction of the original scleritome. The Eohalobia sclerites from the Yanjiahe Formation have an extended and upfolded proximal field with dense wrinkles, which seems to be a weakly mineralized structure and acted as a joint with another sclerite, Ocruranus. Comparing the butterfly-shaped proximal field on a unique sclerite of Eohalobia with the sub-apical field on Ocruranus sclerites suggests that the original scleritome of this group may consist of only two types of sclerites: the Ocruranus-type and the Eohalobia-type. The polygonal structure on the internal mold of Eohalobia sclerites is interpreted herein as the muscle attachment zone; their distribution corresponds well with that of the modern chitons, which provides strong evidence to support the close relationship between the Ocruranus–Eohalobia group and the Polyplacophora.

In order to maintain the security of optical network,it is urgent to research and deploy photonic firewall which can effectively process high-speed optical signals to replace existing electronic firewall which consumes high energy.After a brief review of the principle of photonic firewall,the pattern matching technology based on correlation operation and all-optical logic gates were summarized,and the matching systems was compared according to their advantages and disadvantages.Besides,the realization methods of all-optical logic gates were introduced.Finally,the next research direction and development trend of all-optical pattern matching were prospected:more efficient system structure or non-linear devices with faster response speed.The survey shows that photonic firewall based on all-optical pattern matching has a good application prospect in network security.

The early evolution of the deuterostomes is not well resolved. Here, Topper and colleagues investigate the early Cambrian metazoan Yanjiahella biscarpa, concluding that it is a stem echinoderm, is among the oldest known deuterstomes, and supports an ancestral enteropneust body plan in hemichordates.

Under the framework of computational integral imaging, a multi-image encryption scheme based on the DNA-chaos algorithm is proposed. In this scheme, multiple images are merged to one image by a computational integral imaging algorithm, which significantly improves the efficiency of image encryption. Meanwhile, the computational integral imaging algorithm can merge images at different depth distances, thereby the different depth distances of multiple images can also be used as keys to increase the security of the encryption method. In addition, the high randomness of the chaos algorithm is combined to address the outline effect caused by the DNA encryption algorithm. We have experimentally verified the proposed multi-image encryption scheme. The entropy value of the encrypted image is 7.6227, whereas the entropy value of the merge image with two input images is 3.2886, which greatly reduces the relevance of the image. The simulation results also confirm that the proposed encryption scheme has high key security and can protect against various attacks.

As one of the important parts of modern mechanical equipment, the accurate real-time diagnosis of rolling bearing is particularly important. Traditional fault diagnosis methods have some disadvantages, such as low diagnostic accuracy and difficult fault feature extraction. In this paper, a method combining Wavelet transform (WT) and Deformable Convolutional Neural Network (D-CNN) is proposed to realize accurate real-time fault diagnosis of end-to-end rolling bearing. The vibration signal of rolling bearing is taken as the monitoring target. Firstly, the Orthogonal Matching Pursuit (OMP) algorithm is used to remove the harmonic signal and retain the impact signal and noise. Secondly, the time-frequency map of the signal is obtained by time-frequency transform using Wavelet analysis. Finally, the D-CNN is used for feature extraction and classification. The experimental results show that the accuracy of the method can reach 99.9% under various fault modes, and it can accurately identify the fault of rolling bearing.

Since the first confirmed case of H7N9 infection was reported in China, there have been five epidemic waves of human H7N9 infections between 2013 and 2017. The fifth wave differed from the previous four waves in that highly pathogenic avian influenza (HPAI) H7N9 viruses with multiple basic amino acids at the cleavage site were detected in humans, poultry and environmental samples. The HPAI H7N9 viruses were genetically and antigenically distinct from previous H7N9 viruses. Therefore, a new candidate vaccine virus(CVV) derived from a HPAI A/Guangdong/17SF003/2016-like virus was proposed by the World Health Organization(WHO). According to the WHO recommendations, we constructed a new CVV using reverse genetic technology, with a (6+2) gene constitution. The (6+2) reassortant virus possessed hemagglutinin(HA) with multiple basic amino acids removed and the neuraminidase from A/Guangdong/SF003/2016 in a high-yield A/Puerto Rico/8/34 virus backbone. Sequence analysis confirmed that no mutations had occurred in the HA of V1E1(the initial CVV rescued in Vero cells and followed by passage in eggs), but a mixture of arginine (R)/glycine (G)/isoleucine (I) was detected at position 220 (H3 numbering) in the HA of V1E2 to V1E5 with different percentages. Furthermore, V1E5 showed improved growth characteristics and immunogenicity compared with V1E1, and retained low pathogenicity in chickens and chicken embryos, but the mutation changed its antigenicity. Our study indicates that antigenic changes should be closely monitored during the development of H7N9 CVV in eggs. Additionally, although V1E5 changes the antigenicity, the antisera had some reactivity to previous H7N9 CVVs.

The sub-tree-based optical multicasting scheme provides a spectrum-efficient approach to providing emerging multicast services in optical data center networks. Moreover, multicast services are usually replicated and maintained in multiple geographically distributed data centers to improve its access efficiency and reliability. Therefore, the source data centers of all constructed sub-trees for a multicast demand are not confined to a common data center and can be independently determined by the requested distribution. In this paper, we study the problem of multicast service provisions while leveraging multicast service backups among multiple geographically distributed data centers. A novel distributed sub-tree-based optical multicasting (DST-OM) scheme is proposed. An integer linear program model is developed for the DST-OM scheme with the aim of minimizing the total spectrum consumption of all multicast demands in elastic optical data center networks. We also define the minimum spectrum sub-tree (MSST) problem for the DST-OM scheme. Two modulation-level-aware heuristic algorithms are developed to address the MSST problem. Numerical results show that the DST-OM scheme achieves higher spectrum efficiency and lower blocking probability than the conventional common source sub-tree-based optical multicasting scheme and the single-tree-based optical multicasting scheme.

In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans.

Human infection with avian influenza A H7N9 virus was first identified in March 2013 and represents an ongoing threat to public health. There is a need to optimize serological methods for this new influenza virus. Here, we compared the sensitivity and specificity of the hemagglutinin inhibition (HI), microneutralization (MN), and Western blot (WB) assays for the detection of human antibodies against avian influenza A (H7N9) virus. HI with horse erythrocytes (hRBCs) and a modified MN assay possessed greater sensitivity than turkey erythrocytes and the standard MN assay, respectively. Using these assays, 80% of tested sera from confirmed H7N9 cases developed detectable antibody to H7N9 after 21 days. To balance sensitivity and specificity, we found serum titers of ≥20 (MN) or 160 (HI) samples were most effective in determining seropositive to H7N9 virus. Single serum with HI titers of 20-80 or MN titer of 10 could be validated by each other or WB assay. Unlike serum collected from adult or elderly populations, the antibody response in children with mild disease was low or undetectable. These combinations of assays will be useful in case diagnosis and serologic investigation of human cases.