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Objectives: The objective of this study was to investigate the resistance mechanisms of a multidrug-resistant Salmonella Kentucky ST198 FJ-2064 isolated from a patient in China. Methods: The antimicrobial susceptibility of FJ-2064 was determined by the standard disc dilution and broth microdilution methods. The complete genome of FJ-2064 was sequenced using PacBio and Illumina MiSeq platforms. Polymerase chain reaction (PCR) and S1-PFGE were utilized to confirm the mutation sites and the genomic plasmids, respectively. Results: Isolate FJ-2064 belongs to sequence type ST198 and harboured no visible large plasmids, but was concurrent resistant to 22 detected antimicrobial agents including cefotaxime, ciprofloxacin, and azithromycin. The complete genome sequence identified 20 acquired antibiotic resistance genes (ARGs) and five chromosomal mutations in the gyrA and parC genes of the quinolone resistance determining regions (QRDRs) in FJ-2064. In addition, PCR sequencing confirmed that most of the ARGs were clustered on one multidrug-resistant region and a variant of SGI1-K. In particular, the bla-TEM-1 and bla-CTX−M-55, qnrS1, mph(A) genes, which confer resistance to cephalosporins, quinolones, and macrolides respectively, were all located on the multidrug-resistant region. Conclusions: We have demonstrated one multidrug-resistant region and a variant of SGI1-K in a Salmonella Kentucky ST198 that is co-resistant to cefotaxime, ciprofloxacin, and azithromycin.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the backsplice junction of circATNX1 was screened and delivered by tetrahedral framework nucleic acids (tFNAs) due to their unique compositional and tetrahedral structural features. Our siRNA delivery system demonstrates superior abilities to transfect aging cells, clear intracellular ROS, and enhanced biological safety. Using siRNA–tFNAs to silence circATXN1, aging NPCs exhibit reduced mislocalization of progerin in the cytoplasm and up-regulation of IGF-1R, thereby demonstrating a rejuvenated cellular phenotype and improved mitochondrial function. In vivo, administering an aging cell-adapted siRNA nucleic acid framework delivery system to progerin pathologically expressed premature aging mice (zmpste24−/−) can ameliorate the cellular matrix in the nucleus pulposus tissue, effectively delaying IVDD. This study not only identified circATXN1 functioning as a cell senescence promoter in IVDD for the first time, but also successfully demonstrated its therapeutic potential via a tFNA-based siRNA delivery strategy.

Abstract Spinal cord injury (SCI) causes blood‐spinal cord barrier (BSCB) disruption, leading to secondary damage, such as hemorrhagic infiltration, inflammatory response, and neuronal cell death. It is of great significance to rebuild the BSCB at the early stage of SCI to alleviate the secondary injury for better prognosis. Yet, current research involved in the reconstruction of BSCB is insufficient. Accordingly, we provide a thermosensitive hydrogel‐based G protein‐coupled receptor 124 (GPR124) delivery strategy for rebuilding BSCB. Herein, we firstly found that the expression of GPR124 decreased post‐SCI and demonstrated that treatment with recombinant GPR124 could partially alleviate the disruption of BSCB post‐SCI by restoring tight junctions (TJs) and promoting migration and tube formation of endothelial cells. Interestingly, GPR124 could also boost the energy metabolism of endothelial cells. However, the absence of physicochemical stability restricted the wide usage of GPR124. Hence, we fabricated a thermosensitive heparin‐poloxamer (HP) hydrogel that demonstrated sustained GPR124 production and maintained the bioactivity of GPR124 (HP@124) for rebuilding the BSCB and eventually enhancing functional motor recovery post‐SCI. HP@124 hydrogel can encapsulate GPR124 at the lesion site by injection, providing prolonged release, preserving wounded tissues, and filling injured tissue cavities. Consequently, it induces synergistically efficient integrated regulation by blocking BSCB rupture, decreasing fibrotic scar formation, minimizing inflammatory response, boosting remyelination, and regenerating axons. Mechanistically, giving GPR124 activates energy metabolism via elevating the expression of phosphoenolpyruvate carboxykinase 2 (PCK2), and eventually restores the poor state of endothelial cells. This research demonstrated that early intervention by combining GPR124 with bioactive multifunctional hydrogel may have tremendous promise for restoring locomotor recovery in patients with central nervous system disorders, in addition to a translational approach for the medical therapy of SCI.

IntroductionToxigenic Vibrio cholerae serogroup O1 and O139 are the pathogens responsible for the global cholera epidemic. V. cholerae can settle in the water and spread via the fecal-oral route. Rapid and accurate monitoring of live V. cholerae in environmental water has become an important strategy to prevent and control cholera transmission. Conventional plate counting is widely used to detect viable bacteria but requires time and effort.MethodsThis study aims to develop a new assay that combines triplex droplet digital PCR (ddPCR) with propidium monoazide (PMA) treatment for quantitatively detecting live V. cholerae O1/O139 and cholera enterotoxin. Specific primers and probes were designed according to the conserved regions of gene rfb O1, rfb O139, and ctxA. The amplification procedures and PMA treatment conditions were optimized. The specificity, sensitivity, and ability of PMA-ddPCR to detect viable bacteria-derived DNA were evaluated in simulated seawater samples.Results and DiscussionThe results revealed that the optimal primer concentrations of rfb O1, rfb O139, and ctxA were 1 μM, while the concentrations of the three probes were 0.25, 0.25, and 0.4 μM, respectively. The best annealing temperature was 58°C to obtain the most accurate results. The optimal strategy for distinguishing dead and live bacteria from PMA treatment was incubation at the concentration of 20 μM for 15 min, followed by exposure to a 650-W halogen lamp for 20 min. In pure culture solutions, the limit of detection (LODs) of V. cholerae O1 and O139, and ctxA were 127.91, 120.23 CFU/mL, and 1.5 copies/reaction in PMA-triplex ddPCR, respectively, while the LODs of the three targets were 150.66, 147.57 CFU/mL, and 2 copies/reaction in seawater samples. The PMA-ddPCR sensitivity was about 10 times higher than that of PMA-qPCR. When detecting spiked seawater samples with live bacterial concentrations of 1.53 × 102 and 1.53 × 105 CFU/mL, the assay presented a higher sensitivity (100%, 16/16) than qPCR (50.00%, 8/16) and a perfect specificity (100%, 9/9). These results indicate that the developed PMA-triplex ddPCR is superior to the qPCR regarding sensitivity and specificity and can be used to rapidly detect viable toxigenic V. cholerae O1 and O139 in suspicious seawater samples.

There is little evidence determining whether elderly patients (from 70 to 90 years old) with triple-negative breast cancer could benefit from adjuvant chemotherapy (AC). This study explores the effect of AC in these population following surgery. A total of 4610 patients were identified in the Surveillance, Epidemiology, and End Results database (2010-2018). Multiple imputation by chained equations was performed to impute missing data. Inverse probability of treatment weighting (IPTW) was applied to reduce the selection bias. IPTW-adjusted Kaplan-Meiers survival analysis and Cox proportional hazards models were performed to compare breast cancer specific survival (BCSS) and overall survival (OS) in the two treatment groups. The patients were classified into the chemotherapy (n=1989) and the observation (n=2621) groups. The percentage of patients receiving AC versus observation increased significantly from 2010 to 2018 (estimated annual percentage change, 1.49%; 95%CI, 0.75-2.16%, p=0.002). The 5-year IPTW-adjusted rates of BCSS and OS in AC group were better than that in observation group (BCSS: 82.32% vs. 78.42%, p=0.010; OS: 75.54% vs. 64.65%, p0.050). In conclusion, we presented a BCSS and OS benefit from AC in elderly patients with triple-negative breast cancer (TNBC). AC remained a reasonable treatment approach in these specific patients. For the patients with T1ab, de-escalated treatment would be administrated with caution.

Genome sequencing is widely recognized as a fundamental pillar in genetic research and legal studies of biological phenomena, providing essential insights for genetic investigations and legal analyses of biological events. The field of genome sequencing has experienced significant progress due to rapid improvements in scientific and technological developments. These advancements encompass not only significant improvements in the speed and quality of sequencing but also provide an unparalleled opportunity to explore the subtle complexities of genomes, particularly in the context of rare species. Such a wide range of possibilities has successfully supported the validation of plant gene functions and the refinement of precision breeding methodologies. This expanded scope now includes a comprehensive exploration of the current state and conservation efforts of gymnosperm gene sequencing, offering invaluable insights into their genomic landscapes. This comprehensive review elucidates the trajectory of development and the diverse applications of genome sequencing. It encompasses various domains, including crop breeding, responses to abiotic stress, species evolutionary dynamics, biodiversity, and the unique challenges faced in the conservation and utilization of gymnosperms. It highlights both ongoing challenges and the unveiling of forthcoming developmental trajectories.

Pile composite foundation (PCF) supporting anchorage foundations and immersed tube foundations is subjected to significant vertical and lateral loads, where the PCF design is often controlled by the lateral displacement of PCF head. Therefore, the behavior of lateral loaded PCF is an important issue concerned by engineers, but no published design guidance can be referred. An semi-analytical method is adopted to predict the lateral loaded PCF behaviors, where the reduction factor of the t-th row fp(t) and group efficiency factor fg are induced to account for the group effects. The PCF system is decomposed into fictitious piles and extended soil, and fictitious piles are treated as Bernoulli-Euler beam. The governing equation is formulated based on the compatibility condition of lateral displacement between extended soil and fictitious piles and solved by numerical solution. The analytical results are validated against public theoretical solutions and FEM solutions, and provide very satisfactory results. The PCF behaviors, reduction factor per row fp(t) and group efficiency factor fg are widely investigated by considering some primary influence factors, such as the ratio of pile length to diameter l/d, the ratio of pile spacing to diameter s/d, the number of piles N and the layout form. It is shown that: (1) the surface load on soil elements between piles take a noticeable influence on the deflection and moment distribution along pile shaft; (2) the lateral stiffness of the i-th pile ki, fp(t), fg decrease with increasing s/d, and the l/d has a negligible effect on the fp(t) and fg; (3) the fg of in-line layout is larger than the fg of square array layout and smaller than side-by-side layout form, and fg decrease with the increasing the number of piles N in PCF regardless of pile layout form. The research is expected to provide insights to the practitioners on the lateral loaded PCF design.

Cell-based regenerative therapy utilizes the differentiation potential of stem cells to rejuvenate tissues. But the dynamic fate of stem cells is calling for precise control to optimize their therapeutic efficiency. Stem cell fate is regulated by specific conditions called “microenvironments.” Among the various factors in the microenvironment, the cell-surface glycan acts as a mediator of cell-matrix and cell-cell interactions and manipulates the behavior of cells. Herein, metabolic glycoengineering (MGE) is an easy but powerful technology for remodeling the structure of glycan. By presenting unnatural glycans on the surface, MGE provides us an opportunity to reshape the microenvironment and evoke desired cellular responses. In this review, we firstly focused on the determining role of glycans on cellular activity; then, we introduced how MGE influences glycosylation and subsequently affects cell fate; at last, we outlined the application of MGE in regenerative therapy, especially in the musculoskeletal system, and the future direction of MGE is discussed.

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration (IVDD). However, the increased levels of reactive oxygen species (ROS) in the degenerated region will impede the efficiency of human adipose-derived stem cells (human ADSCs) transplantation therapy. It inhibits human ADSCs proliferation, and increases human ADSCs apoptosis. Herein, we firstly devised a novel amphiphilic copolymer PEG-PAPO, which could self-assemble into a nanosized micelle and load lipophilic kartogenin (KGN), as a single complex (PAKM). It was an injectable esterase-responsive micelle, and showed controlled release ability of KGN and apocynin (APO). Oxidative stimulation promoted the esterase activity in human ADSCs, which accelerate degradation of esterase-responsive micelle. Compared its monomer, the PAKM micelle possessed better bioactivities, which were attributed to their synergistic effect. It enhanced the viability, autophagic activation (P62, LC3 II), ECM-related transcription factor (SOX9), and ECM (Collagen II, Aggrecan) maintenance in human ADSCs. Furthermore, it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats. Therefore, PAKM micelles perform promoting cell survival and differentiation effects, and may be a potential therapeutic agent for IVDD.

The TEOSINTE BRANCHED1 (TBI1), CYCLOIDEA (CYC), and PROLIFERATING CELL NUCLEAR ANTIGEN FACTORS (PCF1 and PCF2) proteins truncated as TCP transcription factors carry conserved basic-helix-loop-helix (bHLH) structure, related to DNA binding functions. Evolutionary history of the TCP genes has shown their presence in early land plants. In this paper, we performed a comparative discussion on the current knowledge of the TCP Transcription Factors in lower and higher plants: their evolutionary history based on the phylogenetics of 849 TCP proteins from 37 plant species, duplication events, and biochemical roles in some of the plants species. Phylogenetics investigations confirmed the classification of TCP TFs into Class I (the PCF1/2), and Class II (the C- clade) factors; the Class II factors were further divided into the CIN- and CYC/TB1- subclade. A trace in the evolution of the TCP Factors revealed an absence of the CYC/TB1subclade in lower plants, and an independent evolution of the CYC/TB1subclade in both eudicot and monocot species. 54% of the total duplication events analyzed were biased towards the dispersed duplication, and we concluded that dispersed duplication events contributed to the expansion of the TCP gene family. Analysis in the TCP factors functional roles confirmed their involvement in various biochemical processes which mainly included promoting cell proliferation in leaves in Class I TCPs, and cell division during plant development in Class II TCP Factors. Apart from growth and development, the TCP Factors were also shown to regulate hormonal and stress response pathways. Although this paper does not exhaust the present knowledge of the TCP Transcription Factors, it provides a base for further exploration of the gene family.

Abstract Exosome therapy is a promising therapeutic approach for intervertebral disc degeneration (IVDD) and achieves its therapeutic effects by regulating metabolic disorders, the microenvironment and cell homeostasis with the sustained release of microRNAs, proteins, and transcription factors. However, the rapid clearance and disruption of exosomes are the two major challenges for the application of exosome therapy in IVDD. Herein, a thermosensitive acellular extracellular matrix (ECM) hydrogel coupled with adipose-derived mesenchymal stem cell (ADSC) exosomes (dECM@exo) that inherits the superior properties of nucleus pulposus tissue and ADSCs was fabricated to ameliorate IVDD. This thermosensitive dECM@exo hydrogel system can provide not only in situ gelation to replenish ECM leakage in nucleus pulposus cells (NPCs) but also an environment for the growth of NPCs. In addition, sustained release of ADSC-derived exosomes from this system regulates matrix synthesis and degradation by regulating matrix metalloproteinases (MMPs) and inhibits pyroptosis by mitigating the inflammatory response in vitro. Animal results demonstrated that the dECM@exo hydrogel system maintained early IVD microenvironment homeostasis and ameliorated IVDD. This functional system can serve as a powerful platform for IVD drug delivery and biotherapy and an alternative therapy for IVDD.

The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation. However, the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied. Herein, we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel (FE) with sustainable and long term extracellular vesicle release (FE@EVs) for improving motor functional recovery after SCI. The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord, thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation, reducing inflammatory reaction, promoting remyelination and axonal regeneration. This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

Ochratoxin A (OTA), frequently existing in the food and feeds, could induce immunotoxicity. Porcine circovirus type 2 (PCV2), as a primary causative agent of porcine circovirus–associated disease, also could induce immunosuppression. However, it is still unknown whether PCV2 infection impacts OTA-induced immunotoxicity. The pigs and porcine alveolar macrophages (PAMs) were used as the model in the present experiment. The results in vivo indicated that PCV2 infection exacerbated OTA-induced immunotoxicity, NF-κB p65 phosphorylation, and TLR4 and MyD88 mRNA and protein expression in spleen. The results in vitro showed that OTA at 7.0 and 9.0 μM decreased cell viability and increased LDH release of PAMs without PCV2 infection. However, with PCV2 infection, OTA at 5.0, 7.0 and 9.0 μM significantly decreased cell viability and increased LDH release compared with absence of PCV2 infection. In addition, OTA at 5.0 and 7.0 μM significantly increased Annexin V/PI-positive rate, apoptosis of nuclear, γ-H2AX foci, IL-1α and TNF-α expression in PAMs with PCV2 infection compared with absence of PCV2 infection. In addition, PCV2 infection enhanced OTA-induced TLR4 and MyD88 mRNA and protein expression and NF-κB p65 phosphorylation. Knockdown of TLR4 alleviated the exacerbating effects of PCV2 infection on OTA-induced cytotoxicity, apoptosis and DNA damage in PAMs. These results indicated that PCV2 infection aggravated OTA-induced immunotoxicity and reduced the dose of OTA-induced immunotoxicity via TLR4/NF-κB p65 signaling pathway, which could provide basis for establishing limits for OTA.

Objective To analyze the combined use of food additives in China, and to assess exposure levels of the common combination of food additives and its cumulative health risks. Methods According to the combined use of food additives in China in the global New Product Database, the maximum allowable amount of food additives of National Food Safety Standards the Use of Food Additives GB 2760-2014, food safety risk monitoring result in China from 2015 to 2019 and the data of the Chinese total dietary study in 2012, a simple distribution method was used to calculate the theoretical and the actual exposure of the common food additives combination in Chinese population and hazard index (HI) method was used to evaluate the cumulative risk. Results Two or more food additives was used in 79.90% of the foods in China, and the highest utilization rate is binary combination, followed by ternary combination and quaternary combination, with a maximum of 29 combination. Through the use of the quaternion combination, the average theoretical daily exposure of sodium benzoate, cyclamate and potassium sorbate in the diet of the general population in China was 1.30, 1.07 and 1.51 mg/kg BW, respectively. The theoretical exposures in the diets of the high food consumption group (P95) were 4.44, 4.69, and 5.19 mg/kg BW, respectively. The proportion of individuals whose average daily theoretical exposure of sodium benzoate, sodium cyclamate and potassium sorbate exceed their corresponding acceptable daily intake (ADI) in the general population was 5.50%. Through cumulative evaluation, it was found that 4 376 individuals had HI≥1, accounting for 13.69% of the surveyed population. According to the actual monitoring data, the average actual daily exposure of sodium benzoate, cyclamate and potassium sorbate in the diet of the general population in China was 0.17, 0.08 and 0.05 mg/kg BW, respectively. The actual exposures in the diets of the high food consumption group (P95) were 0.58, 0.33, and 0.44 mg/kg BW, respectively. The proportion of individuals whose average daily actual exposure of sodium benzoate, sodium cyclamate and potassium sorbate exceed their corresponding ADI in the general population is 0.02%. Through cumulative evaluation, it was found that 12 individuals had HI ≥ 1, accounting for 0.04% of the surveyed population. Conclusion Food additives in China are usually used in multiple forms, the most commonly used additives in binary, ternary and quaternary combinations have low cumulative exposure risks. However, individuals with HI≥1 should adjust their diet.

Purpose: Chemotherapy is the clinically recommended treatment for patients with operable metaplastic breast carcinoma (MBC); however, its impact remains controversial. This study investigated the possible role of chemotherapy in the treatment of MBC.Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify the operable MBC patients. The competing risk analysis along with the propensity score matching (PSM) method was performed to evaluate the effect of chemotherapy. Moreover, a competing risk nomogram was built to identify prognosis in patients with MBC.Results: Of the 1137 patients with MBC, 775 received chemotherapy and 362 did not receive chemotherapy. The 5-year cumulative incidence of breast cancer-specific death (BCSD) showed similar outcomes in both the Chemo and No-Chemo groups (21.1 vs. 24.3%, p = 0.57). Chemotherapy showed no apparent association with BCSD (HR, 1.07; 95% CI, 0.72–1.60; p = 0.72), even after subgroup analysis or PSM. Race, tumor size, lymph node status, and radiation were identified as the significant factors for MBC after a penalized variable selection process. In addition, a competing risk nomogram showed relatively good accuracy of prediction with a C-index of 0.766 (95% CI, 0.700–0.824).Conclusion: Our findings demonstrated that chemotherapy did not improve BCSD for operable MBC patients. Thus, it may indicate the need to reduce exposure to the current chemotherapy strategies for patients with resectable MBC. Additionally, some novel treatment strategies are required urgently to identify and target the potential biomarkers.

Abstract A novel equine parvovirus, equine parvovirus-hepatitis (EqPV-H), was first discovered in a horse that died of equine serum hepatitis in the USA in 2018. EqPV-H was shown to be a novel etiological agent associated with equine serum hepatitis. Following this initial report, no additional studies on EqPV-H have been published. In this study, a total of 143 serum samples were collected from racehorses at 5 separate farms in China and were analyzed to detect EqPV-H DNA via nested PCR. The results indicated a high prevalence of EqPV-H (11.9%, 17/143) in the studied animals. In addition, a remarkably high coinfection rate (58.8%, 10/17) with 2 equine flaviviruses (equine hepacivirus and equine pegivirus) was observed in the EqPV-H positive equines. However, all equines tested negative for Theiler’s disease-associated virus, an etiological agent associated with equine serum hepatitis. The genomes of six field EqPV-H strains were sequenced and analyzed, with the results indicating that the Chinese EqPV-H strains have low genetic diversity and high genetic similarity with the USA EqPV-H strain BCT-01. A phylogenetic analysis demonstrated that the Chinese EqPV-H strains clustered with BCT-01 in the genus Copiparvovirus but were distantly related to another equine parvovirus identified in horse cerebrospinal fluid. In addition, liver enzyme levels were detected in the EqPV-H positive serum samples, and all the values were in the normal range, indicating that infection can occur without concurrent liver disease. This study will promote an understanding of the geographical distribution, genetic diversity, and pathogenicity of EqPV-H.

Malignant cerebral edema (MCE) after an ischemic stroke results in a poor outcome or death. Early prediction of MCE helps to identify subjects that could benefit from a surgical decompressive craniectomy. Net water uptake (NWU) in an ischemic lesion is a predictor of MCE; however, CT perfusion and lesion segmentation are required. This paper proposes a new Image Patch-based Net Water Uptake (IP-NWU) procedure that only uses non-enhanced admission CT and does not need lesion segmentation. IP-NWU is calculated by comparing the density of ischemic and contralateral normal patches selected from the middle cerebral artery (MCA) area using standard reference images. We also compared IP-NWU with the Segmented Region-based NWU (SR-NWU) procedure in which segmented ischemic regions from follow-up CT images are overlaid onto admission images. Furthermore, IP-NWU and its combination with imaging features are used to construct predictive models of MCE with a radiomics approach. In total, 116 patients with an MCA infarction (39 with MCE and 77 without MCE) were included in the study. IP-NWU was significantly higher for patients with MCE than those without MCE (p < 0.05). IP-NWU can predict MCE with an AUC of 0.86. There was no significant difference between IP-NWU and SR-NWU, nor between their predictive efficacy for MCE. The inter-reader and interoperation agreement of IP-NWU was exceptional according to the Intraclass Correlation Coefficient (ICC) analysis (inter-reader: ICC = 0.92; interoperation: ICC = 0.95). By combining IP-NWU with imaging features through a random forest classifier, the radiomics model achieved the highest AUC (0.96). In summary, IP-NWU and radiomics models that combine IP-NWU with imaging features can precisely predict MCE using only admission non-enhanced CT images scanned within 24 h from onset.

The canine influenza virus (CIV) outbreaks have raised concerns as they pose a threat to the health of dogs. The successful construction of a canine influenza (CI) infection model is essential to study the CIV. Here we investigated the pathogenicity of different infectious doses of H3N2 CIV in Beagle dogs. Thirty-seven healthy Beagle dogs were used in the experiment and were infected with 103, 104, 105, and 106 50% egg-infectious doses (EID50). Compared to the dogs in the other three groups, those in the 106 EID50 group presented with obvious clinical symptoms, high virus titer, and typical pathological changes. Considering the ensemble of clinical scores, body temperature, virus shedding, lung lesions, pathological section scores, and visceral virus titers, we determined that 106 EID50 is the minimum infectious dose for the Beagle infection model. The other three infectious doses had almost no clinical symptoms. These results indicate that 106 EID50 is the minimum infectious dose of H3N2 CIV that can cause obvious clinical manifestations and pathological changes associated with CI in Beagle dogs. The theoretical framework developed in this research will guide the establishment of an infection model of CIV for future research.

Abstract Background China has the world’s largest tea plantation area in the world. To sustain high yields of the tea, multiple pesticides are used on tea crops to control pests. Organophosphorus (OP) pesticides are among the most widely used types of agricultural pesticides in China. As tea is a significant potential source of exposure to pesticide residues, the public concern has increased in relation to pesticide residues found in tea in China. The aim of the study was to estimate cumulative dietary exposure to OP residues from tea infusion for Chinese tea consumers to determine whether exposure to OP residues from tea infusion is a cause of health concern for tea consumers in China. Methods OP residue data were obtained from the China National Monitoring Program on Food Safety (2013–2014), encompassing 1687 tea samples from 12 provinces. Tea consumption data were obtained from the China National Nutrient and Health Survey (2002), comprising 506 tea consumers aged 15–82 years. The transfer rates of residues from tea leaves into tea infusions were obtained from the literature. The relative potency factor (RPF) approach was used to estimate acute cumulative exposure to 20 OP residues from tea infusion using methamidophos as the index compound. Dietary exposure was calculated in a probabilistic way. Results For tea consumers, the mean and the 99.9th percentile (P99.9) of cumulative dietary exposure to OP residues from tea infusion equalled 0.08 and 1.08 μg/kg bw/d. When compared with the acute reference dose (ARfD), 10 μg/kg bw/d for methamidophos, this accounts for 0.8 and 10.8% of the ARfD. Conclusions Even when considering OP residues from vegetables, fruits and other foods, there are no health concerns based on acute dietary exposure to OP residues from tea infusion. However, it is necessary to strengthen the management of the OP pesticides used on tea in China to reduce the risk of chronic dietary exposure to OPs from tea infusion.

Colletotrichum has a broad host range and causes major yield losses of crops. The fungus Colletotrichum gloeosporioides is associated with anthracnose on Chinese fir. In this study, we present a high-quality draft genome sequence of C. gloeosporioides sensu stricto SMCG1#C, providing a reference genomic data for further research on anthracnose of Chinese fir and other hosts.

Background The microRNAs (miRNAs) have been validated as prognostic markers in many cancers. Here, we aimed at developing a miRNA-based signature for predicting the prognosis of esophagus adenocarcinoma (EAC). Methods The RNA-sequencing data set of EAC was downloaded from The Cancer Genome Atlas (TCGA). Eighty-four patients with EAC were classified into a training set and a test set randomly. Using univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO), we identified prognostic factors and constructed a prognostic miRNA signature. The accuracy of the signature was evaluated by the receiver operating characteristic (ROC) curve. Result In general, in the training set, six miRNAs (hsa-mir-425, hsa-let-7b, hsa-mir-23a, hsa-mir-3074, hsa-mir-424 and hsa-mir-505) displayed good prognostic power as markers of overall survival for EAC patients. Relative to patients in the low-risk group, those assigned to the high-risk group according to their risk scores of the designed miRNA model displayed reduced overall survival. This 6-miRNA model was validated in test and entire set. The area under curve (AUC) for ROC at 3 years was 0.959, 0.840, and 0.868 in training, test, and entire set, respectively. Molecular functional analysis and pathway enrichment analysis indicated that the target messenger RNAs associated with 6-miRNA signature were closely related to several pathways involved in carcinogenesis, especially cell cycle. Conclusion In summary, a novel 6-miRNA expression-based prognostic signature derived from the EAC data of TCGA was constructed and validated for predicting the prognosis of EAC.

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

The Hopkinson pressure bar is widely used to measure the reflected pressure of blast waves over a short distance. However, dispersion effects will occur when the elastic stress waves propagate in the pressure bar due to lateral inertia, and there will be errors between the signals obtained from the sensors and the actual loading. For the free surface velocity measured in our system, we developed a local phase-amplitude joint correction method to convert the measured velocity into the average reflected pressure of a shock wave at the impact end of the bar, considering factors such as propagation modes of the elastic wave, the frequency components’ time of arrival, velocity variation over the bar axis, and the stress–velocity relationship. Firstly, the Pochhammer–Chree frequency equation is calculated numerically, and the first to fourth orders of phase velocity, group velocity, normalized frequency, and propagation time curves of elastic wave propagation in 35CrMnSiA steel are obtained. Secondly, the phase and amplitude correction formulas for calculating average reflected pressure from center velocity are derived based on the propagation mode of the axial elastic wave in the pressure bar by analyzing the time-frequency combined spectrum obtained by short-time Fourier transform. Thirdly, a local phase-amplitude joint correction algorithm based on propagation mode is proposed in detail. The experimental tests and data analyses are carried out for eight sets of pressure bar. The results show that this method can identify the propagation mode of elastic waves in the bar intuitively and clearly. The first three orders of propagation modes are stimulated in the bar 04, while only the first order of propagation is stimulated in the other eight bars. The local phase-amplitude joint correction algorithm can avoid correcting the component of the non-axial elastic wave. The rising edge of the average stress curve on the impact surface of bar 01 and bar 04 is corrected from 4.13 μs and 4.09 μs to 2.70 μs, respectively.

Equine hepacivirus (EqHV), equine pegivirus (EPgV) and Theiler's disease-associated virus (TDAV) are three novel equine viruses in the family Flaviviridae. EqHV and EPgV have been identified to circulate in the equine population worldwide, whereas TDAV has not been detected in equines since the first reported case. To date, no studies have focused on investigating EqHV, EPgV and TDAV in commercial equine sera or equine blood products in China. Considering the potential threat of EqHV, EPgV and TDAV to biosecurity and considering their possible influences on research results, equine sera for cell culture propagation and pregnant mare serum gonadotropin (PMSG) were purchased from different companies in China and investigated for EqHV, EPgV and TDAV in this study. By performing nested PCR or two rounds of PCR targeting the viral NS3 gene, four serum samples were confirmed to be EqHV-, EPgV-, or TDAV-RNA positive; all of the PMSG samples were negative for these three viruses. Subsequent sequencing results indicated that the serum samples contained multiple viral variants of EqHV, EPgV or TDAV, and a genetic analysis based on the partial NS3 gene of the three equine viruses was performed. Our study is the first to confirm the presence of EqHV, EPgV and TDAV in equine sera for cell culture propagation that is commercially available in China and provides the first demonstration of the presence of TDAV in China.

Glyptostrobus pensilis, belonging to the monotypic genus Glyptostrobus (Family: Cupressaceae), is an ancient conifer that is naturally distributed in low-lying wet areas. Here, we report the complete chloroplast (cp) genome sequence (132,239 bp) of G. pensilis. The G. pensilis cp genome is similar in gene content, organization and genome structure to the sequenced cp genomes from other cupressophytes, especially with respect to the loss of the inverted repeat region A (IRA). Through phylogenetic analysis, we demonstrated that the genus Glyptostrobus is closely related to the genus Cryptomeria, supporting previous findings based on physiological characteristics. Since IRs play an important role in stabilize cp genome and conifer cp genomes lost different IR regions after splitting in two clades (cupressophytes and Pinaceae), we performed cp genome rearrangement analysis and found more extensive cp genome rearrangements among the species of cupressophytes relative to Pinaceae. Additional repeat analysis indicated that cupressophytes cp genomes contained less potential functional repeats, especially in Cupressaceae, compared with Pinaceae. These results suggested that dynamics of cp genome rearrangement in conifers differed since the two clades, Pinaceae and cupressophytes, lost IR copies independently and developed different repeats to complement the residual IRs. In addition, we identified 170 perfect simple sequence repeats that will be useful in future research focusing on the evolution of genetic diversity and conservation of genetic variation for this endangered species in the wild.

Land cover classification is the most important element of land cover mapping and is a key input to many societal benefits. Traditional classification methods require a large amount of remotely sensed images, which are time consuming and labour intensive. Recently, crowdsourcing geographic information (CGI), including geo-tagged photos and other sources, has been widely used with lower costs, but still requires extensive labour for data classification. Alternatively, CGI textual information is available from online sources containing land cover information, and it provides a useful source for land cover classification. However, the major challenge of utilising CGI is its uneven spatial distributions in land cover regions, leading to less reliability of regions for land cover classification with sparsely distributed CGI. Moreover, classifying various unorganised CGI texts automatically in each land cover region is another challenge. This paper investigates a faster and more automated method that does not require remotely sensed images for land cover classification. Spatial clustering is employed for CGI to reduce the effect of uneven spatial distributions by extracting land cover regions with high density of CGI. To classify unorganised various CGI texts in each extracted region, land cover topics are calculated using topic model. As a case study, we applied this method using points of interest (POIs) as CGI to classify land cover in Shandong province. The classification result using our proposed method achieved an overall accuracy of approximately 80%, providing evidence that CGI with textual information has a great potential for land cover classification.

Salvia miltiorrhiza is an important medicinal plant with great economic and medicinal value. The complete chloroplast (cp) genome sequence of Salvia miltiorrhiza, the first sequenced member of the Lamiaceae family, is reported here. The genome is 151,328 bp in length and exhibits a typical quadripartite structure of the large (LSC, 82,695 bp) and small (SSC, 17,555 bp) single-copy regions, separated by a pair of inverted repeats (IRs, 25,539 bp). It contains 114 unique genes, including 80 protein-coding genes, 30 tRNAs and four rRNAs. The genome structure, gene order, GC content and codon usage are similar to the typical angiosperm cp genomes. Four forward, three inverted and seven tandem repeats were detected in the Salvia miltiorrhiza cp genome. Simple sequence repeat (SSR) analysis among the 30 asterid cp genomes revealed that most SSRs are AT-rich, which contribute to the overall AT richness of these cp genomes. Additionally, fewer SSRs are distributed in the protein-coding sequences compared to the non-coding regions, indicating an uneven distribution of SSRs within the cp genomes. Entire cp genome comparison of Salvia miltiorrhiza and three other Lamiales cp genomes showed a high degree of sequence similarity and a relatively high divergence of intergenic spacers. Sequence divergence analysis discovered the ten most divergent and ten most conserved genes as well as their length variation, which will be helpful for phylogenetic studies in asterids. Our analysis also supports that both regional and functional constraints affect gene sequence evolution. Further, phylogenetic analysis demonstrated a sister relationship between Salvia miltiorrhiza and Sesamum indicum. The complete cp genome sequence of Salvia miltiorrhiza reported in this paper will facilitate population, phylogenetic and cp genetic engineering studies of this medicinal plant.

The presence of duplicates introduced by PCR amplification is a major issue in paired short reads from next-generation sequencing platforms. These duplicates might have a serious impact on research applications, such as scaffolding in whole-genome sequencing and discovering large-scale genome variations, and are usually removed. We present FastUniq as a fast de novo tool for removal of duplicates in paired short reads. FastUniq identifies duplicates by comparing sequences between read pairs and does not require complete genome sequences as prerequisites. FastUniq is capable of simultaneously handling reads with different lengths and results in highly efficient running time, which increases linearly at an average speed of 87 million reads per 10 minutes. FastUniq is freely available at http://sourceforge.net/projects/fastuniq/.

Fusarium species cause serious diseases in cereal staple food crops such as wheat and maize. Currently, the mechanisms underlying resistance to Fusarium-caused diseases are still largely unknown. In the present study, we employed a combined proteomic and transcriptomic approach to investigate wheat genes responding to F. graminearum infection that causes Fusarium head blight (FHB). We found a total of 163 genes and 37 proteins that were induced by infection. These genes and proteins were associated with signaling pathways mediated by salicylic acid (SA), jasmonic acid (JA), ethylene (ET), calcium ions, phosphatidic acid (PA), as well as with reactive oxygen species (ROS) production and scavenging, antimicrobial compound synthesis, detoxification, and cell wall fortification. We compared the time-course expression profiles between FHB-resistant Wangshuibai plants and susceptible Meh0106 mutant plants of a selected set of genes that are critical to the plants' resistance and defense reactions. A biphasic phenomenon was observed during the first 24 h after inoculation (hai) in the resistant plants. The SA and Ca(2+) signaling pathways were activated within 6 hai followed by the JA mediated defense signaling activated around 12 hai. ET signaling was activated between these two phases. Genes for PA and ROS synthesis were induced during the SA and JA phases, respectively. The delayed activation of the SA defense pathway in the mutant was associated with its susceptibility. After F. graminearum infection, the endogenous contents of SA and JA in Wangshuibai and the mutant changed in a manner similar to the investigated genes corresponding to the individual pathways. A few genes for resistance-related cell modification and phytoalexin production were also identified. This study provided important clues for designing strategies to curb diseases caused by Fusarium.

To solve the problem of single working frequency of traditional reflective focused metasurface, a dual-band reflective focused metasurface is proposed, which can realize independent focusing characteristics at 7.25 GHz and 20.5 GHz. The metasurface unit is composed of metal elements combined by a split-ring resonant structure working at 7.25 GHz and an elliptical resonant structure working at 20.5 GHz in the same plane, dielectric substrate, and ground. Dual-band independent control and 360° phase coverage are achieved by adjusting the dimensions of unit. The surface current distribution also verifies the rationality of the designed metasurface element. Based on the principle of quasi-optical path, a dual-band reflective focused metasurface with independent focusing characteristics is designed. Through full-wave simulation, the focusing efficiency at 7.25 GHz and 20.5 GHz is calculated by Poynting theorem, which are 56.9% and 57.5%, respectively. The proposed dual-band metasurface has the characteristics of simple structure and low profile without multi-layer stacking and metal through-holes. [ABSTRACT FROM AUTHOR]