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Abstract Background Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion. Methods Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort. Results In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively. Conclusions The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.

Objective: This study aimed to explore the incidence of abnormal catheter positioning and the effectiveness and safety of intravascular adjustment or removal of abnormally positioned catheters through percutaneous punctures. Materials and methods: A retrospective analysis was conducted on 58 patients with abnormal catheter positioning, treated between January 2009 and June 2019. Intravascular adjustment of the migrated catheters and removal of the fractured catheters were performed through percutaneous puncture using a pigtail catheter, cobra catheter, and gooseneck snare. Results: Of the 58 cases, there were 23 cases of catheter migration and 35 cases of catheter fracture. The incidence of abnormal catheter positioning was 3.0%, corresponding to 1.2% migrations and 1.8% fractures. Among the 23 cases of migration, 1 case did not require adjustment and another underwent unsuccessful adjustment. The rate of successful adjustment of migrated catheters was 91.3%, whereas the rate of successful removal of fractured catheters was 100%. No surgery-related complications were observed either immediately or during the 1-month follow-up period. Conclusions: This study showed that the incidence of abnormal catheter positioning is low. Intravascular techniques used for the adjustment or removal of abnormally placed catheters are safe, efficient, and minimally invasive.

BackgroundWhether irAEs can predict the efficacy of PD-1 inhibitors in cholangiocarcinoma (CCA) has not been assessed. Therefore, this study aims to investigate the correlation between irAEs and the therapeutic effect of PD-1 inhibitors combination therapy in patients with advanced CCA.MethodsAll patients with CCA who were consecutively admitted to the inpatient unit of our hospital and received PD-1 inhibitors combination therapy between September 2020 and April 2022 were screened. In total, 106 patients with CCA were screened out. We then followed up these patients until October 2022. Due to perioperative use (n=28), less than 2 cycles of PD-1 inhibitor therapy (n=9), incomplete data (n=8) and no pathological report (n=2), 59 patients were included in the final analysis. The patients were divided into the irAEs cohort and the non-irAEs cohort according to whether they experienced irAEs or not. The Log-Rank test was performed to compare the difference in survival time between these two cohorts. We then applied multivariate COX regression analysis to investigate whether irAEs were independent prognostic factors for survival in patients with advanced CCA.ResultsFinally, 32 patients were included in the irAEs cohort and 27 patients in the non-irAEs cohort. A total of 32 patients (54.2%) had any-grade irAEs, of which 4 patients (6.8%) had grade 3-4 irAEs. The most common irAEs were thyroid toxicity (30.5%) and dermatologic toxicity (30.5%). There were no notable differences in demographics and clinical characteristics between the irAEs and non-irAEs cohorts, except for total bilirubin level (P=0.026) and relapse (P=0.016). The disease control rate (DCR) in the irAEs cohort was higher than in the non-irAEs cohort (90.6% vs 70.4%, P=0.047). Median overall survival (OS) and median progression-free survival (PFS) were better in the irAEs cohort than in the non-irAEs cohort (OS: 21.2 vs 10.0 months, P

BackgroundThe emergence of highly drug-resistant K. pneumoniae, has become a major public health challenge. In this work, we aim to investigate the diversity of species and sequence types (STs) of clinical Klebsiella isolates and to characterize the prevalence and structure of class 1 integrons.MethodsBased on the whole genome sequencing, species identification was performed by 16S rRNA gene homology and average nucleotide identity (ANI) analysis. STs were determined in accordance with the international MLST schemes for K. pneumoniae and K. variicola. Integron characterization and comparative genomic analysis were performed using various bioinformatic tools.ResultsSpecies identification showed that the 167 isolates belonged to four species: K. pneumoniae, K. variicola subsp. variicola, K. quasipneumoniae and K. aerogenes. Thirty-six known and 5 novel STs were identified in K. pneumoniae, and 10 novel STs were identified in K. variicola subsp. variicola. Class 1 integrons were found in 57.49% (96/167) of the isolates, and a total of 169 resistance gene cassettes encoding 19 types of resistance genes, including carbapenem resistance gene (blaIPM-4) and class D β-lactamases gene (blaOXA-1 and blaOXA-10), were identified. Among the 17 complete genomes, 29 class 1 integrons from 12 groups were found, only 1 group was encoded on chromosomes. Interestingly, one plasmid (pKP167-261) carrying two copies of approximately 19-kb IS26-Int1 complex resistance region that contains an integron and a multidrug resistance gene fragment.ConclusionThe results of this work demonstrated that the species and STs of the clinical Klebsiella isolates were more complex by the whole genome sequence analysis than by the traditional laboratory methods. Finding of the new structure of MGEs related to the resistance genes indicates the great importance of deeply exploring the molecular mechanisms of bacterial multidrug resistance.

Myocardial fibrosis can lead to ischemic damage of the myocardium, which can be life-threatening in severe cases. Cardiac fibroblast (CF) transdifferentiation is an important process in myocardial fibrosis. Fucoxanthin (FX) plays a key role in ameliorating myocardial fibrosis; however, its mechanism of action is not fully understood. This study investigated the role of FX in the angiotensin II (Ang II)-induced transdifferentiation of CFs and its potential mechanisms of action. We found that FX inhibited Ang II-induced transdifferentiation of CFs. Simultaneously, FX downregulated bromodomain-containing protein 4 (BRD4) expression in CFs and increased nuclear expression of nuclear factorerythroid 2-related factor 2 (Nrf2). FX reverses AngII-induced inhibition of the Keap1/Nrf2/HO-1 pathway and elevates the level of reactive oxygen species (ROS). FX failed to reverse Ang II-induced changes in fibrosis-associated proteins and ROS levels after Nrf2 silencing. BRD4 silencing reversed the inhibitory effect of Ang II on the Keap1/Nrf2/HO-1 antioxidant signalling pathway. In conclusion, we demonstrated that FX inhibited Ang II-induced transdifferentiation of CFs and that this effect may be related to the activation of the Keap1/Nrf2/HO-1 pathway by reducing BRD4 expression and, ultimately, oxidative stress.

The density-based applied spatial clustering algorithm is an algorithm based on high-density interconnected regions, which discovers class clusters of arbitrary shapes in noisy data sets and is widely used. However, it suffers from slow computation speed due to large-scale disk I/O and clustering bias due to uneven density class clusters and poor parameter search ability. To address these problems, a parallel density clustering algorithm based on an improved fruit fly optimization algorithm and Spark memory iteration is proposed. The proposed algorithm first divides the data grid using an irregular dynamic density region partitioning strategy. Then, a hybrid fruit fly particle swarm algorithm based on a genetic optimization mechanism is proposed to achieve dynamic optimization seeking for parameters in local clustering to improve the clustering effect of local clustering. Finally, the local merging of samples in irregularly bounded grid cells under each partition is achieved by designing a custom clustering merging strategy. The experiments show that the improved algorithm is generally applicable to the clustering of different shape class clusters and larger scale data and has obvious improvement in accuracy and parallel efficiency.

Background: Port-A-Cath systems (PCS) are safe and convenient devices for long-term infusion in patients with malignant tumors. This study retrospectively analyzed the complications from PCS and their management. Methods: Data of 1695 adults (641 males and 1054 females) with malignant tumors who underwent PCS implantation in our center from January 1, 2009 to December 31, 2019 who had complete follow-up records were collected in this study. The early and late complications and corresponding treatments were studied. Results: A total of 1716 PCSs were implanted; 21 patients underwent 2 implantations each. The success rate was 100% and no severe complications occurred during implantation. The overall occurrence rate of post-implantation complications was 18.5% (318/1716); 5.5% (94/1716) were early complications and 13.0% (224/1716) were late complications. A total of 451 PCSs were removed, of which 398 were removed due to the end of chemotherapy, while 53 were removed because of complications. A total of 4 deaths occurred from these complications. Conclusions: The incidence of intra- and post-operative complications is low. In most cases, complications can be effectively controlled without the removal of the PCS and regular follow-up and maintenance are critical.

Suckling mouse inoculation is an important method that has been used for years to isolate viruses from ticks; however, this method has usually been briefly described in the literature on a case-by-case basis upon successful isolation rather than providing extensive details. This study describes the procedure from preparation of tick homogenates to identification of virus isolation using the suckling mouse inoculation method. The transient and persistent features were characterized and the incidence of manifestations that developed in the suckling mice, especially in mice from which viruses were isolated, is reported. We identified 22 symptoms that developed in mice, including 13 transient symptoms that recovered by the end of the observation period and 7 persistent symptoms that the mice suffered from throughout the observation period. Persistent symptoms (lateral positioning and dead) and transient symptoms (malaise, emaciation, and difficulty turning over) were the main symptoms based on the high overall incidence. Moreover, we showed that mice from which viruses were isolated had a concentrated period and advanced days of disease onset. This study provides detailed information necessary for better use of suckling mouse inoculation to isolate viruses from ticks, which may benefit optimization of this method to identify, discover, and acquire tick-borne viruses.

We report the isolation of Tamdy virus from Hyalomma asiaticum ticks in northwest China and serologic evidence of human Tamdy virus infection in the same region. These findings highlight the need to further investigate a potential causal relationship between Tamdy virus and febrile illnesses of unknown etiology in that region.

Abstract Low pathogenic avian influenza viruses (LPAIVs) have been widespread in poultry and wild birds throughout the world for many decades. LPAIV infections are usually asymptomatic or cause subclinical symptoms. However, the genetic reassortment of LPAIVs may generate novel viruses with increased virulence and cross-species transmission, posing potential risks to public health. To evaluate the epidemic potential and infection landscape of LPAIVs in Guangxi Province, China, we collected and analyzed throat and cloacal swab samples from chickens, ducks and geese from the live poultry markets on a regular basis from 2016 to 2019. Among the 7,567 samples, 974 (12.87%) were LPAIVs-positive, with 890 single and 84 mixed infections. Higher yearly isolation rates were observed in 2017 and 2018. Additionally, geese had the highest isolation rate, followed by ducks and chickens. Seasonally, spring had the highest isolation rate. Subtype H3, H4, H6 and H9 viruses were detected over prolonged periods, while H1 and H11 viruses were detected transiently. The predominant subtypes in chickens, ducks and geese were H9, H3, and H6, respectively. The 84 mixed infection samples contained 22 combinations. Most mixed infections involved two subtypes, with H3 + H4 as the most common combination. Our study provides important epidemiological data regarding the isolation rates, distributions of prevalent subtypes and mixed infections of LPAIVs. These results will improve our knowledge and ability to control epidemics, guide disease management strategies and provide early awareness of newly emerged AIV reassortants with pandemic potential.

The SARS-CoV-2 spike (S) protein mediates viral entry by binding of its receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor and mutations of the S protein may have a great impact on virus transmissibility. Here, the authors characterize the interactions of six different SARS-CoV-2 RBD variants among them Alpha, Beta and Gamma and present crystal structures of these ACE2-RBD complexes.

Purpose: Our research mainly evaluates the clinical efficacy of two surgical methods in the treatment of osteonecrosis of the femoral head (ONFH) at ARCO stage II, aiming to provide optimal hip-preserving treatment of ONFH. Method: From October 2018 to September 2020, 48 patients (59 hips) met the inclusion criteria and randomized. 24 cases (29 hips) in experimental group were treated with minimally-invasive fibular supporting of T-type; 24 cases (30 hips) in control group were treated with traditional bloody iliac flap metastasis. We will compare some intraoperative and postoperative conditions. Result: The operation time in experimental group was 37 (6) minutes, in control group was 130 (21.75) minutes; the length of surgical incision in two groups was 3.7 (0.7) cm and 12.85 (2.68) cm. The intraoperative blood loss in two groups was 69 (21) ml and 363 (87) ml; the postoperative VAS score of the experimental group on day 1, day 3, day 7 after surgery was 5.5 (2), 3.5 (1), 0 (1); the control group was 6 (1.75), 4 (1), 3 (1). The data differences between above groups have statistically significant. The follow-up time of two groups was (33.86 ± 5.66) months and (35.67 ± 4.69) months. The bone graft healing time in two groups was (14.21 ± 1.93) months and (13.83 ± 2.34) months. The Harris hip scores of two groups at the last follow-up were 90 (7.5) and 86.5 (8.5). The survival rates of two groups were 79.31% (23/29) and 76.67% (23/30). The difference was no statistically significant in above groups (P > 0.05). Conclusion: The two different bone graft implantation showed satisfactory early outcomes. Compared to the control group, the experimental group has the advantages of lesser pain, lesser blood loss, lesser trauma and shorter operation time. It may be a choice as bone graft for the treatment of ONFH at early stage.

IntroductionLelliottia amnigena, a bacterium usually isolated from natural environments, may cause human infections and has been suggested to be naturally resistant to second- and third-generation cephalosporins.MethodsIn this study, we determined the whole-genome sequence of an isolate, L. Amnigena P13, isolated from animal farm sewage. On the basis of genome sequence analysis, susceptibility testing, molecular cloning, and enzyme kinetic parameter analysis, we identified a novel chromosome-encoded AmpC β-lactamase, LAQ-1.Results and DiscussionblaLAQ-1 is resistant to penicillin G, ampicillin, and several first- to fourth-generation cephalosporins, such as cefazolin, cefoxitin and cefepime. The MIC levels of some β-lactams, such as cefoxitin, cefepime, aztreonam and cefazolin, for the recombinant clone (pUCP24-blaLAQ-1/DH5α) increased by approximately 4- to 64-fold compared with those of the control strain (pUCP24/DH5α). The kinetic properties of LAQ-1, with the highest catalytic activity observed toward piperacillin, were basically the same as those of typical class C β-lactamases, and avibactam had a strong inhibitory effect on its hydrolytic activity. The genetic background of blaLAQ-1 was relatively conserved, and no mobile genetic element (MGE) was found around it. The plasmid pP13-67 of L. amnigena P13 harbored 12 resistance genes [qnrS1, aph(6)-Id, aadA2, sul1, sul2,blaTEM-1, qacEΔ1, dfrA12, tetA and floR] related to different mobile genetic elements within an ~22 kb multidrug resistance region. The multidrug resistance region shared the highest nucleotide sequence similarities with those of the chromosomes or plasmids of different bacterial species, indicating the possibility of horizontal transfer of these resistance genes among different bacterial species.

Hepatocellular carcinoma (HCC) remains a major challenge to clinicians due to its unacceptably high mortality and morbidity. The etiology of HCC is multi-faceted, including viral infection, alcoholism and non-alcoholic fatty liver disease. Dysregulated host immunity contributes to tumorigenesis among these susceptible individuals with pre-existing condition(s). IL-32 and IL-34 are key cytokines driving the development of chronic inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, as well as chronic liver diseases. IL-32 and IL-34 play an important role augmenting the development of HCC, due to their direct influence over host inflammation, however, new roles for these cytokines in HCC are emerging. Here we comprehensively review the latest research for IL-32 and IL-34 in HCC, identifying a subset of potential therapeutic targets for use in precision medicine.

Abstract Background Canine distemper caused by canine distemper virus that belongs to the Morbillivirus genus of the Paramyxoviridae family is still a global epidemic significant infectious disease, especially in pet dogs in China and serious harm to the development of the dog industry. It has been known that apoptosis caused by the canine distemper virus can show in culture cells, lymphoid tissues, and the cerebellum. However, its occurrence in brain tissue cells remains unclear. To investigate the relationship among canine distemper infecting brain tissues, apoptosis in brain tissue cells, and demyelinating pathogenesis was investigated. Methods 16 naturally infected dogs that exhibited clinical signs of CD and tested positive for the anti-CDV monoclonal antibody and six healthy dogs that served as the control, were used in the research. Brain specimens were divided into the cerebrum, brain stem, and cerebellum embedded in paraffin and made the sections respectively. Approximately 5 µm-thick sections were stained by hematoxylin–eosin, methyl green pyronin, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique, and immunohistochemistry. CDV nucleocapsid protein was detected by immune streptavidin-biotinylated peroxidase complex. Results Alterations in the brain tissues of CDV-infected dogs involved both various cells and nerve fibers. CDV had varying degrees of cytotropism to all brain tissue cells; apoptosis also occurred in all brain cells, especially in the endothelia of cerebral vessels, astrocytes, oligodendrocytes, and ependymal cells, the more serious infection, the more obvious apoptosis. Serious infections also involved the pyramidal and Purkinje cells. The nervous fibers exhibited demyelinating lesions (showed small multifocal vacuole), and some axonal neuron atrophy gradually disappeared (formed large vacuole). Conclusions Apoptosis in brain tissue cells was mainly related to the propagation path and cytotropism of CDV. The apoptosis of astrocytes, oligodendrocytes, and some neurons may play a significant role in the demyelinating pathogenesis in dogs with acute canine distemper. A lot of diverse nervous signs shown in the clinic may be related to different neuron apoptosis.

Many domestic animals, among them dogs, have been infected with SARS-CoV-2 during the COVID-19 pandemic. Here, the authors present the crystal structure of the SARS-CoV-2 spike protein receptor binding domain (RBD) bound to its receptor, dog angiotensin-converting enzyme 2 (dACE2), and show that the RBD N501Y mutation increases the infectivity and host range of SARS-CoV-2, which highlights the need to monitor emerging SARS-CoV-2 mutations in domestic animals.

Avian reovirus (ARV) infection can lead to severe immunosuppression, complications, and secondary diseases, causing immense economic losses to the poultry industry. In-depth study of the mechanism by which the innate immune system combats ARV infection, especially the antiviral effect mediated by interferon, is needed to prevent and contain ARV infection. In this study, ARV strain S1133 was used to artificially infect 7-day-old specific pathogen–free chickens. The results indicated that ARV rapidly proliferated in the immune organs, including the spleen, bursa of Fabricius, and thymus. The viral load peaked early in the infection and led to varying degrees of pathological damage to tissues and organs. Real-time quantitative PCR revealed that the mRNA levels of interferon and multiple interferon-stimulated genes (ISGs) in the spleen, bursa of Fabricius, and thymus were upregulated to varying degrees in the early stage of infection. Among the ISGs, IFIT5, and Mx were the most upregulated in various tissues and organs, suggesting that they are important ISGs for host resistance to ARV infection. Further investigation of the role of IFIT5 in ARV infection showed that overexpression of the IFIT5 gene inhibited ARV replication, whereas inhibition of the endogenously expressed IFIT5 gene by siRNA promoted ARV replication. IFIT5 may be a positive feedback regulator of the innate immune signaling pathways during ARV infection and may induce IFN-α production by promoting the expression of MAD5 and MAVS to exert its antiviral effect. The results of this study help explain the innate immune regulatory mechanism of ARV infection and reveal the important role of IFIT5 in inhibiting ARV replication, which has important theoretical significance and practical application value for the prevention and control of ARV infection.

Protein-glutaminase (PG), a deamidation enzyme commercially derived from Chryseobacterium proteolyticum, is used to improve the solubility and other functional properties of food proteins. In this study, a new PG-producing strain, Chryseobacterium cucumeris ZYF120413-7, was isolated from soil, and it had a high PG yield and a short culture time. It gave the maximum PG activity with 0.557 U/ml on Cbz-Gln-Gly after 12 h of culture, indicating that it was more suitable for PG production. The enzyme activity recovery and purification fold were 32.95% and 161.95-fold, respectively, with a specific activity of 27.37 U/mg. The PG was a pre-pro-protein with a 16 amino acids putative signal peptide, a pro-PG of 118 amino acids, and a mature PG of 185 amino acids. The amino acid sequence identity of PG from strain ZYF120413-7 was 74 and 45%, respectively, to that of PG from C. proteolyticum 9670T and BH-PG. The optimum reaction pH and temperature of PG was 6 and 60°C, respectively. Enzyme activity was inhibited by Cu2+. The optimum PG substrate was Cbz-Gln-Gly, and the Km and Vmax values were 1.68 mM and 1.41 μM mg protein−1 min−1, respectively. Degree of deamidation (DD) of soy protein isolate (SPI) treated by purified PG was 40.75% within the first 2 h and 52.35% after 18 h. These results demonstrated that the PG from C. cucumeris ZYF120413-7 was a promising protein-deamidating enzyme for improving the functionality of food proteins.

Previous studies reported that Aflatoxin B1 (AFB1) causes cell damage through its metabolite aflatoxin B1–8, 9-epoxide (AFBO), which is catalyzed by CYP450 enzymes. AFBO can be detoxified by glutathione S transferase (GST). Ferulic acid (FA) is known for its antioxidant capacity and intestinal protective function. However, the mechanism of AFB1 causing duodenal injury and the role of FA in AFB1-induced intestinal damage remains unclear. In this study, rats were exposed to AFB1 and treated with FA for 30 days. The results showed that I) FA alleviated the histopathological changes of duodenum and the ultrastructural changes of tight junctions between duodenal epithelial cells induced by AFB1. II) FA reduced the content of AFB1-ALB adduct in blood. III) The low expression of tight junction proteins (Claudin-1 and ZO-1) and the high expression of ROCK1 and ROCK2 induced by AFB1 were significantly reversed by FA. IV) The high expression of CYP2A6 and CYP3A4 were significantly down-regulated by FA, and the activity of GST was promoted by FA. V) The binding affinity of FA to CYP2A6 is very similar to the binding affinity of AFB1 to CYP2A6, which meaning that there is a competitive relationship between FA and AFB1 when conjugating to CYP2A6. These results suggested that FA proved effective in alleviating AFB1-induced duodenal barrier damage via up-regulating tight junction proteins, down-regulating ROCK, competing CYP450 enzyme, and activating GST in duodenal epithelial cells of rats.

Abstract Previously, we had cross-sectionally explored the characteristics of T cell receptor (TCR) repertoires from occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) patients, now we further analyzed the dynamic features of OMDT TCR repertoires. Peripheral blood TCR β-chain complementarity-determining region 3 (CDR3) genes were detected with the high throughput sequencing in 24 OMDT cases in their acute, chronic and recovery stages, respectively, and in 24 trichloroethylene-exposed healthy controls. The TCR repertoire diversity, TRBV/TRBD/TRBJ gene usage and combination, frequencies of CDR3 nucleotide (nt) and amino acid (aa) sequences in the cases in different stages and in the controls were analyzed. TRBV6-4 and TRBV7-9 frequencies significantly differed between the cases and controls (both P

Abstract Background Trichloroethylene (TCE) hypersensitivity syndrome (THS) is a dose-independent and potentially life-threatening disease. In this study, we sought to identify THS-related miRNAs and evaluate its potential clinical value. Methods Serum samples of five patients and five matched TCE contacts were used for screening differential miRNAs. Another 34 patients and 34 matched TCE contacts were used for verifying significantly differential miRNAs with SYBR™ Green PCR and MGB PCR. The diagnostic model based on these miRNAs was established via the support vector machine (SVM) algorithm. Correlation between differential miRNAs and liver function was analyzed via the Spearman correlation test. Results A total of 69 miRNAs was found to be differentially expressed. MiR-21-5p and miR-339-5p were verified to have significant higher expressions in patients. The sensitivity, specificity and accuracy of disease model were 100, 75 and 86%, respectively. The two miRNAs showed significant correlations with liver function. Conclusion These findings suggested that miRNAs profiles in serum of THS patients had changed significantly, and miR-21-5p and miR-339-5p were associated with THS.

ABSTRACT: Paper and plastic bags have been mainly used in fruit bagging of pineapple production. However, they are often discarded as agricultural wastes after harvest of pineapple fruit and threaten environment. In this study, effects of white non-woven fabric bag, expandable polyethylene bag, black plastic bag and kraft paper bag on fruit quality of pineapple cv. ‘MD-2’ were investigated. Results showed that fruits with fruit bagging showed no sunburn. When expandable polyethylene bag was used, fruits of pineapple cv. ‘MD-2’ showed better external qualities, nutrition qualities and texture properties. Expandable polyethylene bag made of degradable and recyclable materials could be recommended as a promising practice to reduce agricultural waste in pineapple production.

Despite few human cases of tick-borne encephalitis virus (TBEV), high rates of TBEV seroprevalence were reported among humans and animals in Xinjiang Uygur Autonomous Region in Northwestern China. In this study, the Karshi virus (KSIV) was identified and isolated from Hyalomma asiaticum ticks in Xinjiang. It belongs to the genus Flavivirus of the family Flaviviridae and is closely related to TBEV. KSIV infects cell lines from humans, other mammals and ticks, and causes encephalitis in suckling mice. High minimum infection rates (4.96%) with KSIV were detected among tick groups. KSIV infections have occurred in sheep and marmots, resulting in antibody-positive rates of 2.43 and 2.56%, respectively. We further found that, of the KSIV antibody-positive serum samples from animals, 13.9% had TBEV exposure showing cross-reaction to KSIV, and 11.1% had KSIV infection resulting in cross-reaction to TBEV; 8.3% were likely to have co-exposure to both viruses (or may be infected with one of them and present cross-reactivity with the other). The results revealed a substantial KSIV prevalence among ticks in Xinjiang, indicating exposure of animals to KSIV and TBEV. The findings implied misinterpretation of the high rates of TBEV seroprevalence among humans and animals in previous studies. There is a need to develop detection methods to distinguish KSIV from TBEV and to perform an in-depth investigation of KSIV and TBEV prevalence and incidence in Northwestern China, which would enhance our preparation to provide medical treatment of emerging diseases caused by tick-borne viral pathogens such as KSIV.

ObjectiveStudies have shown a correlation between gut microbiota and anxiety and depression levels. However, these studies are mainly animal studies or clinical studies of non-cancer patients, there is still a lack of relevant studies in cancer patients. The main objective of this trial was to analyze the correlation between probiotics and anxiety and depression levels in cancer patients.MethodsWe screened all cancer patients consecutively admitted to the inpatient department of the First Affiliated Hospital, Zhejiang University School of Medicine in May 2020. A total of 292 cancer patients met our inclusion criteria. Then, we followed up all patients for 24 weeks. Patients who had incomplete data or loss of follow-up were excluded. In addition, in patients who took probiotics, those did not take probiotics consistently or did not take specific probiotics were excluded. Ultimately, the number of patients enrolled was 82 in probiotics cohort and 100 in non-probiotics cohort. The 17-item Hamilton Depression Scale (HAMD-17) questionnaire was used to measure the depression levels of the patients, and we also used Hamilton Anxiety Scale (HAMA) questionnaire to assess the patients’ anxiety levels. A logistic regression model was used to analyze whether the difference in baseline data of two cohorts would affect the final result.ResultsDemographic and clinical characteristics of all cancer patients enrolled in probiotics cohort and non-probiotics cohort were similar except the cancer therapy (P = 0.004). According to the HAMA score, we divided cancer patients into non-anxiety group (HAMA score < 14) and anxiety group (HAMA score ≥ 14). Similarly, cancer patients were also divided into non-depression group (HAMD-17 score ≤ 7) and depression group (HAMD-17 score > 7). The results demonstrated that there was no statistical difference in the proportion of patients with anxiety (6.1 and 13.0%, respectively, P = 0.121) and depression (30.5 and 23.0%, respectively, P = 0.254) between probiotics and non-probiotics cohorts. The results of logistic regression model analysis further proved that the baseline difference in cancer therapy did not affect the conclusions.ConclusionOur results still suggest that there is no significant correlation between probiotics and anxiety and depression levels in cancer patients. Therefore, we do not recommend supplementing probiotics for cancer patients to prevent anxiety and depression. Moreover, high-quality RCTs are also needed to further confirm the conclusions of this study.

Abstract Background The World Health Organization (WHO) in 2015 stated that every effort should be made to provide cesarean delivery (CD) for women in need. In China, the two-child policy largely prompts the number of advanced age childbirth, which raises the possibility of an increasing number of women who need a c-section. The aim of this study was to assess the trends in the overall and medical indication-classified CD rates in the era of the two-child policy in Jiangsu, China. Methods A retrospective cross-sectional study of 291,448 women who delivered in 11 hospitals in Jiangsu province between 2012 and 2019 was conducted. Medical cesarean indication for each woman was ascertained by manually reviewing the medical records. The 291,448 women were divided into two subgroups according to the presence of the indications: the indicated group (7.80%) and the non-indicated group (92.20%). We then fitted joinpoint regression and log-binomial regression models to estimate trends in the CD rates across the study period. Results The overall CD rate was observed with a declining trend from 52.51% in 2012–2015 to 49.76% in 2016–2019 (adjusted RR, 0.92; 95% CI, 0.91–0.93; P

Introduction: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma (HCC). We aimed to compare the clinical outcomes of lenvatinib plus drug-eluting beads transarterial chemoembolization (DEB-TACE) versus lenvatinib alone in real-world practice. Methods: This retrospective analysis included 142 consecutive patients who received lenvatinib plus DEB-TACE and 69 patients who received lenvatinib alone as first-line treatment from 15 Chinese academic centers from Nov 2018 to Nov 2019. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) evaluated by mRECIST criteria, and safety profiles were compared between the two groups. Results: The median OS and PFS were significantly longer in the combined therapy group than in the monotherapy group in whole cohort (median OS, 15.9 vs 8.6 months, p=0.0022; median PFS, 8.6 vs 4.4 months, p

ObjectiveAlthough the pathogenesis of hepatocellular carcinoma (HCC) is still unclear, hepatitis C virus (HCV) infection is considered a common cause of HCC. It has been reported that DDX60L can inhibit HCV replication, but its role in HCC is still poorly understood.MethodsThe expression levels of DDX60L in HCC tissues and in tissues adjacent to the tumor and their correlation with the clinicopathological features of patients were analyzed. We also used Kaplan–Meier curves of overall survival (OS) with Cox regression analysis and log-rank test to investigate the prognostic value of DDX60L in HCC. We further performed cell proliferation, Transwell, and wound healing assays to elucidate the role of DDX60L in HCC using the siRNA-DDX60L Hep3B or HCCLM3 cell line.ResultsUnivariate analysis showed that sex, Edmondson grade, microvascular invasion, tumor stage (III–IV/I–II), AFP, and DDX60L expression were strongly associated with the prognosis of HCC patients. The results of multivariate analysis further suggested that DDX60L might be an independent prognostic factor for OS in patients with HCC (Pmoderate/low = 0.015, Phigh/low = 0.011). The low DDX60L expression in HCC patients with no-metastasis, age ≥55 years, tumor size 20 μg/L, and multiple tumor was associated with poorer prognosis (P

Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification technique that can be used to amplify target genes at a constant temperature, and it has several advantages, including convenience, specificity and sensitivity. However, due to the special interpretation methods of this technology for reaction results, all the previously reported LAMP detection methods have been restricted to identifying a single target, which limits the application of this technology. In this study, we modified conventional LAMP to include a quencher-fluorophore composite probe complementary to the F1c segment of the inner primer FIP; upon strand separation, a gain in the visible fluorescent signal was observed. The probes could be labeled with different fluorophores, showing different colors at the corresponding wavelengths. Therefore, this multiplex LAMP (mLAMP) assay can simultaneously detect 1-3 target sequences in a single LAMP reaction tube, and the results are more accurate and intuitive. In this study, we comprehensively demonstrated a single-reaction mLAMP assay for the robust detection of three cattle viruses without nonspecific amplification of other related pathogenic cattle viruses. The detection limit of this mLAMP assay was as low as 526-2477 copies/reaction for the recombinant plasmids. It is expected that this mLAMP assay can be widely used in clinical diagnosis.

Objectives. The statistical characteristics of incubation time of COVID-19 are studied comprehensively in this paper. We studied the mean value and tail characteristic of incubation time. Also, the difference in incubation time is studied in different age groups, different genders, and different contact modes. Methods. We analyzed the data by a lognormal distribution. Tail characteristics of incubation time are studied by the excess function. The difference in incubation time between different age groups, different genders, and different contact modes is studied by one-way ANOVA. Results. The results showed that the mean value of incubation time is about 12.6 days, and the standard deviation is about 6.1 days. The incubation time of 95% of patients was within 24 days. Some patients have a very long incubation time according to the excess function. The incubation time was not related to age and gender but related to the suspected contact modes. Conclusions. The mean value of incubation time is consistent with the actual situation. The above results are a reasonable explanation for the phenomenon of super-long incubation time in some patients and the development trend of epidemic situations.

Abstract Effects of post annealing on the physical and electrical properties of solar-blind polycrystalline gallium oxide (Ga2O3) ultraviolet photodetectors on the sapphire substrate are investigated. The grain size of poly-Ga2O3 becomes larger with the post annealing temperature (PAT) increasing from 800 °C to 1000 °C, but it gets smaller with further raising PAT to 1100 °C. A blue shift is observed at the absorption edge of the transmittance spectra of Ga2O3 on sapphire as increasing PAT, due to the incorporation of Al from the sapphire substrate into Ga2O3 to form (Al x Ga1–x )2O3. The high-resolution X-ray diffraction and transmittance spectra measurement indicate that the substitutional Al composition and bandgap of (Al x Ga1–x )2O3 annealed at 1100 °C can be above 0.30 and 5.10 eV, respectively. The R max of the sample annealed at 1000 °C increases about 500% compared to the as-deposited device, and the sample annealed at 1000 °C has short rise time and decay time of 0.148 s and 0.067 s, respectively. This work may pave a way for the fabrication of poly-Ga2O3 ultraviolet photodetector and find a method to improve responsivity and speed of response.

Abstract The H3 subtype of avian influenza virus (AIV) is widespread in avian species and is frequently isolated in surveillance projects; thus, we have developed a more effective diagnostic approach of a monoclonal antibody (mAb)-based sandwich ELISA for the H3 AIV detection. First, we have produced the essential reagent of mAb against AIV H3 strains with the development of an mAb-Mouse immunization with a purified H3-subtype AIV strain and cell fusion to generate hybridoma cells. These cells were screened with hemagglutination inhibition (HI) tests, and optimal cells were subcloned. We chose a hybridoma cell line that steadily secreted a specific H3-subtype AIV mAb, designated 9F12, that belongs to the IgG1 subclass and has a K-type light chain. 9F12 was shown to bind specifically to the H3-subtype AIV antigen by both immunofluorescence assay and Western blot analysis. Finally, a 9F12-based sandwich ELISA was successfully developed and used to specifically test for this antigen. The sandwich ELISA conditions were optimized, and the specificity and sensitivity were validated. The results for clinical sample detection were consistent with viral isolation. Consequently, the 9F12-based sandwich ELISA is a specific, sensitive, robust, rapid and versatile diagnostic tool for H3-subtype AIV and provides a promising strategy for effective influenza virus prevention and control.

Background/Aims Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking. Methods : A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models. Results : The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson’s capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p

Antibody repertoire sequencing (Rep-seq) has been widely used to reveal repertoire dynamics and to interrogate antibodies of interest at single nucleotide-level resolution. However, polymerase chain reaction (PCR) amplification introduces extensive artifacts including chimeras and nucleotide errors, leading to false discovery of antibodies and incorrect assessment of somatic hypermutations (SHMs) which subsequently mislead downstream investigations. Here, a novel approach named DUMPArts, which improves the accuracy of antibody repertoires by labeling each sample with dual barcodes and each molecule with dual unique molecular identifiers (UMIs) via minimal PCR amplification to remove artifacts, is developed. Tested by ultra-deep Rep-seq data, DUMPArts removed inter-sample chimeras, which cause artifactual shared clones and constitute approximately 15% of reads in the library, as well as intra-sample chimeras with erroneous SHMs and constituting approximately 20% of the reads, and corrected base errors and amplification biases by consensus building. The removal of these artifacts will provide an accurate assessment of antibody repertoires and benefit related studies, especially mAb discovery and antibody-guided vaccine design.

Nonpolar/polar block copolymer materials can be used to develop high-performance dielectric elastomer materials. At present, there is no method to accurately predict its dielectric constant, which is not conducive to improving related research and development efficiency. For this, styrene–butadienestyrene triblock copolymer (SBS) block copolymer grafted modified by thioglycolic acid (TGA) is chosen as the research object. We propose a hybrid calculation method combining the group contribution method, the connectivity index method, and the dipole moment fluctuation method. The connectivity index method and the dipole moment fluctuation method calculate the dielectric constants of nonpolar and polar repeat units to provide accurate basic data for the group contribution method. In the calculation process, the Vogel model completes the mutual conversion between dielectric constant and molar polarizability. Both theoretical calculation and experimental verification show that the dielectric constant of SBS-TGA increases with the grafting rate. We found the correlation between theoretical calculations and experimental values and confirmed that the applicable frequency range of this method is 1 kHz–1000 kHz. This method can be extended to predict the dielectric constant of other polymers and improve development efficiency.

Gemstones usually contain inclusions as the natural hallmark of their formation. Studies on inclusions may contribute to our understanding of the gem and better adapt to the gems and jewelry industry. In this study, we applied advanced 3D Raman mapping and high-resolution X-ray computed tomography (HRXCT) and conducted a thorough experiment on one emerald with a special trapiche pattern containing a colorless core, solid minerals, and fluids. Hematite and magnetite were identified as metallic minerals by the Raman spectrum. The hexagonal core is beryl, and the voids are primarily filled with CO2 and N2. HRXCT demonstrated a visualized distribution of these inclusions within the gem host by reconstructing a 3D illustration. Further calculation of the volume of inclusions regarding the host showed that the minerals take up 0.07%, void 0.03%, and the hexagonal core 8.25%. The combined application of Raman-Mapping and X-ray Micro Computed Tomography proved to be a very promising technique for tracing the gemstones by characterizing the unique inclusions (identification and morphology) within the gem host.

β-amylase (BAM) plays an important role in plant development and response to abiotic stresses. In this study, 5 DoBAM members were identified in yam (Dioscorea opposita Thunb.). A novel β-amylase gene BAM1, (named DoBAM1), was isolated from yam varieties Bikeqi and Dahechangyu. The open reading frame (ORF) of DoBAM1 is 2806 bp and encodes 543 amino acids. Subcellular localization analysis indicates that DoBAM1 localizes to the cell membrane and cytoplasm. In the yam variety Dahechangyu, the starch content, β-amylase activity, and expression of DoBAM1 were characterized and found to all be higher than in Bikeqi. DoBAM1 overexpression in tobacco is shown to promote the accumulation of soluble sugar and chlorophyll content and to increase the activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and β-amylase. Under cold treatment, we observed the induced upregulation of DoBAM1 and lower starch content and malondialdehyde (MDA) accumulation than in WT plants. In conclusion, these results demonstrate that DoBAM1 overexpression plays an advanced role in cold tolerance, at least in part by raising the levels of soluble sugars that are capable of acting as osmolytes or antioxidants.

Odorous gas (e.g. atmospheric ammonia) in low ventilation public places, such as public toilets and waste transfer stations, causes severe health problems. Many technologies are developed to purify the atmospheric ammonia, among which the microbial agents are supposed to be a green and economical approach. In this study, we developed a yeast, Pichia sp. J1, and a lactic acid bacterium (LAB), Lactobacillus paracasei B1, co-culture agent for atmospheric ammonia removing. The on-site application results indicated the yeast and LAB mixed fermented agent had a maximum ammonia removing efficiency of 98.78%, which is significantly higher than the pure cultures (78.93% for B1 and 75.00% for J1), indicating the co-culture agent is an excellent biological product for ammonia removal. The excellent performance of the agent is closely related to the synergy behaviors between the yeast and LAB. In the co-culture agents, some of the LAB cells adhered closely to the yeast, and the growth and lactic acid producing ability of LAB were significantly promoted by yeast. Genomic analysis indicated the complementary of nutrients, i.e. carbon and nitrogen resources, signal transduction, and adhesion proteins (regulates adhesion behavior) played roles in regulating the synergy effects. Our study offers a novel biological solution of odorous gas purification.

Peroxidase-mediated chemokinetic therapy (CDT) can effectively resist bacteria; however, factors such as the high dosage of drugs seriously limit the antibacterial effect. Herein, CuFeS2 nanoparticles (NPs) nanozyme antibacterial system with the photothermal effect and peroxidase-like catalytic activity are proposed as a combined antibacterial agent with biosafety, high-efficiency, and broad-spectrum antibacterial ability. In addition, the as-obtained CuFeS2 NPs with a low doses of Cu+ and Fe3+ can change the permeability of bacterial cell membranes and break the antioxidant balance by consuming intracellular glutathione (GSH), which results in more conducive ROS production. Meanwhile, the photothermal heating can regulate the CuFeS2 NPs close to their optimal reaction temperature (60 °C) to release more hydroxyl radical in low concentrations of H2O2 (100 µM). The proposed CuFeS2 NPs-based antibacterial system achieve more than 99% inactivation efficiency of methicillin-resistant Staphylococcus aureus (106 CFU mL−1 MRSA), hyperspectral bacteria β-Escherichia coli (106 CFU mL−1 ESBL) and Pseudomonas aeruginosa (106 CFU mL−1 PA), even at low concentration (2 μg mL−1), which is superior to those of the conventional CuO NPs at 4 mg mL−1 reported in the literature. In vivo experiments further confirm that CuFeS2 NPs can effectively treat wounds infected by MRSA and promote the wound healing. This study demonstrates that excellent antibacterial ability and good biocompatibility make CuFeS2 NPs a potential anti-infection nanozyme with broad application prospects.

Wuhan was the very first city hit by SARS-CoV-2. Accordingly, the patients who experienced the longest phase of convalescence following COVID-19 reside here.

Objective Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma (EC) has not been analyzed yet. Methods Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor (ER), insulin receptor (InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin. Results Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation, cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice. Conclusions Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α, promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.

Abstract Background Circular RNAs (circRNAs) play important roles in tumourigenesis and tumour progression. However, the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC) are largely unclear. Methods The expression profiles of circRNAs in HCC were identified through microarray analysis and were validated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. The circular structure of candidate circRNA was confirmed through Sanger sequencing, divergent primer PCR, and RNase R treatments. Proliferation of HCC cells was evaluated in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was demonstrated using dual-luciferase reporter and RNA immunoprecipitation assays. Results CircSETD3 (hsa_circRNA_0000567/hsa_circRNA_101436) was significantly downregulated in HCC tissues and cell lines. Low expression of circSETD3 in HCC tissues significantly predicted an unfavourable prognosis and was correlated with larger tumour size and poor differentiation of HCC in patients. In vitro experiments showed that circSETD3 inhibited the proliferation of HCC cells and induced G1/S arrest in HCC cells. In vivo studies revealed that circSETD3 was stably overexpressed in a xenograft mouse model and inhibited the growth of HCC. Furthermore, we demonstrated that circSETD3 acts as a sponge for miR-421 and verified that mitogen-activated protein kinase (MAPK)14 is a novel target of miR-421. Conclusion CircSETD3 is a novel tumour suppressor of HCC and is a valuable prognostic biomarker. Moreover, circSETD3 inhibits the growth of HCC partly through the circSETD3/miR-421/MAPK14 pathway.

In this paper, we proposed a logistic regression model with lp,q regularization that could give a group sparse solution. The model could be applied to variable-selection problems with sparse group structures. In the context of big data, the solutions for practical problems are often group sparse, so it is necessary to study this kind of model. We defined the model from three perspectives: theoretical, algorithmic and numeric. From the theoretical perspective, by introducing the notion of the group restricted eigenvalue condition, we gave the oracle inequality, which was an important property for the variable-selection problems. The global recovery bound was also established for the logistic regression model with lp,q regularization. From the algorithmic perspective, we applied the well-known alternating direction method of multipliers (ADMM) algorithm to solve the model. The subproblems for the ADMM algorithm were solved effectively. From the numerical perspective, we performed experiments for simulated data and real data in the factor stock selection. We employed the ADMM algorithm that we presented in the paper to solve the model. The numerical results were also presented. We found that the model was effective in terms of variable selection and prediction.

Weaning plays an important role in many animal processes, including the development of the rumen microbiota in ruminants. Attaining a better understanding of the development of the rumen microbial community at different weaning stages can aid the identification of the optimal weaning age. We investigated the effects of weaning age on ruminal bacterial and archaeal communities in Hu lambs. Thirty male Hu lambs were randomly assigned to two weaning-age groups: a group weaned at 30 days of age (W30) and a group weaned at 45 days of age (W45), with each group having five replicate pens. On the weaning day (day 30 for W30 and day 45 for W45) and at 5 days postweaning [day 35 for W30 (PW30) and day 50 for W45 (PW45)], one lamb from each replicate was randomly selected and sacrificed. Rumen contents were collected to examine the ruminal microbiota. Compared to W30, PW30 had a decreased relative abundance of Bacteroidetes. At genus level, the extended milk replacer feeding (W45 vs. W30) increased the relative abundance of Ruminococcus while decreased that of Prevotella and Dialister. Compared to W30, PW30 exhibited decreased relative abundances of Prevotella, Dialister and Bacteroides but an increased unclassified Coriobacteriaceae. No significant difference was noted in the detected archaeal taxa among the animals. The function “biosynthesis of secondary metabolites” was less predominant in PW30 than in W30, whereas the opposite held true for “metabolism of cofactors and vitamins.” Some bacterial genera were significantly correlated with rumen volatile fatty acid (VFA) concentration or other animal measures, including negative correlations between ruminal VFA concentration and unclassified Mogibacteriaceae and unclassified Veillonellaceae; positive correlations of ruminal papillae length with Fibrobacter and unclassified Lachnospiraceae, but negative correlations with Mitsuokella and Succiniclasticum; and negative correlations between plasma D-lactate concentration and Prevotella, unclassified Paraprevotellaceae, and Desulfovibrio. Our results revealed that the ruminal bacterial community underwent larger changes over time in lambs weaned at 30 days of age than in lambs weaned half a month later. Thus, extending milk replacer feeding to 45 days weaning was recommended from the perspective of the rumen microbial community in the Hu lamb industry.

Avian reovirus (ARV) can induce many diseases as well as immunosuppression in chickens, severely endangering the poultry industry. Interferons (IFNs) play an antiviral role by inducing the expression of interferon-stimulated genes (ISGs). The effect of ARV infection on the expression of host ISGs is unclear. Specific-pathogen-free (SPF) chickens were infected with ARV strain S1133 in this study, and real time quantitative PCR was used to detect changes in the dynamic expression of IFNs and common ISGs in joints of SPF chickens. The results showed that the transcription levels of IFNA, IFNB, and several ISGs, including myxovirus resistance (MX), interferon-induced transmembrane protein 3 (IFITM3), protein kinase R (PKR), oligoadenylate synthase (OAS), interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), interferon-stimulated gene 12 (ISG12), virus inhibitory protein (VIPERIN), interferon-alpha-inducible protein 6 (IFI6), and integrin-associated protein (CD47), were upregulated in joints on days 1–7 of infection (the levels of increase of MX, IFIT5, OAS, VIPERIN, ISG12, and IFI6 were the most significant, at hundreds-fold). In addition, the expression levels of the ISGs encoding zinc finger protein 313 (ZFP313), and DNA damage–inducible transcript 4 (DDIT4) increased suddenly on the 1st or 2nd day, then decreased to control levels. The ARV viral load in chicken joints rapidly increased after 1 day of viral challenge, and the viral load remained high within 6 days of viral challenge. The ARV viral load sharply decreased starting on day 7. These results indicate that in SPF chicken joints, many ISGs have mRNA expression patterns that are basically consistent with the viral load in joints. IFNA, IFNB, and the ISGs MX, IFITM3, PKR, OAS, IFIT5, ISG12, VIPERIN, IFI6, and CD47 play important roles in defending against ARV invasion, inhibiting ARV replication and proliferation, and promoting virus clearance. These results enrich our understanding of the innate immune response mechanisms of hosts against ARV infection and provide a theoretical basis for prevention and control of ARV infection.

Metagenomic next-generation sequencing (mNGS) has become a widely used technology that can accurately detect individual pathogens. This prospective study was performed between February 2019 and September 2019 in one of the largest clinical neurosurgery centers in China. The study aimed to evaluate the performance of mNGS on cerebrospinal fluid (CSF) from neurosurgical patients for the diagnosis of external ventricular and lumbar drainage (EVD/LD)-associated ventriculitis and meningitis (VM). We collected CSF specimens from neurosurgical patients with EVD/LD for more than 24 h to perform conventional microbiological studies and mNGS analyses in a pairwise manner. We also investigated the usefulness of mNGS of CSF for the diagnosis of EVD/LD-associated VM. In total, 102 patients were enrolled in this study and divided into three groups, including confirmed VM (cVM) (39), suspected VM (sVM) (49), and non-VM (nVM) (14) groups. Of all the patients, mNGS detected 21 Gram-positive bacteria, 20 Gram-negative bacteria, and five fungi. The three primary bacteria detected were Staphylococcus epidermidis (9), Acinetobacter baumannii (5), and Staphylococcus aureus (3). The mNGS-positive coincidence rate of confirmed EVD/LD-associated VM was 61.54% (24/39), and the negative coincidence rate of the nVM group was 100% (14/14). Of 15 VM pathogens not identified by mNGS in the cVM group, eight were negative with mNGS and seven were inconsistent with the conventional microbiological identification results. In addition, mNGS identified pathogens in 22 cases that were negative using conventional methods; of them, 10 patients received a favorable clinical treatment; thus, showing the benefit of mNGS-guided therapy.

A previously unidentified chicken parvovirus (ChPV) and turkey parvovirus (TuPV) strain, associated with runting-stunting syndrome (RSS) and poultry enteritis and mortality syndrome (PEMS) in turkeys, is now prevalent among chickens in China. In this study, a large-scale surveillance of parvoviruses in chickens and turkeys using conserved PCR assays was performed. We assessed the prevalence of ChPV/TuPV in commercial chicken and turkey farms in China between 2014 and 2019. Parvoviruses were prevalent in 51.73% (1,795/3,470) of commercial chicken and turkey farms in Guangxi, China. The highest frequency of ChPV positive samples tested by PCR occurred in chickens that were broiler chickens 64.18% (1,041/1,622) compared with breeder chickens 38.75% (572/1,476) and layer hens 38.89% (112/288), and TuPV was detected in 70/84 (83.33%). Native and exotic chicken species were both prevalent in commercial farms in southern China, and exotic broiler chickens had a higher positive rate with 88.10% (148/168), while native chickens were 50.00% (1,465/2,930). The environmental samples from poultry houses tested positive for ChPV and TuPV were 47.05% (415/874). Samples from open house flocks had higher prevalence rates of ChPV than those of closed house flocks (Table 5), among which those from the open house showed 84.16% (85/101) positivity, those from litter showed 62.86% (44/70) positivity, and those from drinking water showed 50.00% (56/112) positivity, whereas those from the closed house litter were 53.57% (60/112), those from swabs were 50.18% (138/275), and those from drinking water were 15.69% (32/204). Samples collected during spring were more frequently ChPV/ TuPV positive than those collected during other seasons. This study is the first report regarding the epidemiological surveillance of ChPV and TuPV in chicken/turkey flocks in Guangxi, China. Our results suggest that ChPV and TuPV are widely distributed in commercial fowl in Guangxi. These findings highlight the need for further epidemiological and genetic research on ChPV and TuPV in this area.

Occupational cancer causes a large number of deaths every year, posing a great threat to public health in China and abroad. Occupational cancer surveillance can help to dynamically monitor and predict the trend of cancer occurrence and provide basic reference for the formulation of occupational cancer prevention and treatment measures. Occupational cancer surveillance started late in China relative to developed western countries, but formed its own characteristics through years of development of legislation and institutional reform, and large-scale epidemiological investigations and laboratory research. Occupational cancer surveillance is currently a part of cancer surveillance system of the National Cancer Center, as well as an integral part of occupational disease surveillance in China. It generally includes not only cancer incidence surveillance, but also cancer-related occupational risk factor surveillance, and surveillance of effects of occupational cancer prevention, treatment, and intervention. The methods of occupational cancer surveillance in China include passive monitoring, active monitoring, and sentinel monitoring. These methods have their respective advantages and disadvantages and would be best to be combined in practice. The rapid development of economy and technology, and continuous advancement of hospital informatization, especially the establishment and application of big data on occupational cancer, may point out directions for the development of occupational cancer surveillance in the future. Occupational cancer prevention and control in China still has a long way to go and the destination is to achieve primary prevention for occupational cancer.

Host tropism and cell entry of pathogenic coronaviruses are mediated by their envelope spike (S) proteins. Here the authors present structural analyses of trimeric MERS-CoV and SARS-CoV S proteins in pre-fusion conformation, and reveal two states of the receptor binding domain that suggest new avenues for the generation of neutralizing antibodies.

To date, nine neuraminidase (NA) subtypes of avian influenza virus (AIV) have been identified in poultry and wild birds. Rapid and effective methods for differentiating these nine NA subtypes are needed. We developed and validated a rapid, sensitive, and robust method utilizing a GeXP analyzer-based multiplex RT-PCR assay and capillary electrophoresis for the simultaneous differentiation of the N1 to N9 subtypes in a single-tube reaction. Ten pairs of primers–nine subtype-specific pairs and one pan-AIV pair–were screened and used to establish the GeXP multiplex RT-PCR assay. A single subtype was detected using the developed GeXP assay; the N1 to N9 AIV subtypes individually generated two target peaks: the NA subtype-specific peak and the general AIV peak. Different concentrations of multiplexed subtypes were tested with this GeXP assay and the peaks of the corresponding NA subtypes were generated, suggesting that this GeXP assay is useful for identifying NA subtypes in mixed samples. Moreover, no peaks were generated for other important avian viruses, indicating negative results and validating the lack of cross-reactions between AIV subtypes and other avian pathogens. RNA templates synthesized through in vitro transcription were used to analyze the sensitivity of the assay; the limit of detection was 100 copies per reaction mixture. The results obtained from clinical samples using this GeXP method were consistent with the results of the neuraminidase inhibition (NI) test, and the ability of the GeXP assay to identify mixed infections was superior to amplicon sequencing of isolated viruses. In conclusion, this GeXP assay is proposed as a specific, sensitive, rapid, high-throughput, and versatile diagnostic tool for nine NA subtypes of AIV.