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Rabbits can efficiently utilize plant fibers that are indigestible to humans, and hence may contribute to the alleviation of feed-food competition. Therefore, it is economically and ecologically important to genetically improve the growth performance and feed efficiency of meat rabbits. In this study, we combined pedigree, genomic, and gut microbiota data to estimate genetic and microbial parameters for nine growth and feed efficiency traits of 739 New Zealand White rabbits, including body weight (BW) at 35 (BW35), 70 (BW70), and 84 (BW84) days of age, and average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) within two age intervals of 35-70 days (ADG70, FCR70, and RFI70) and 35-84 days (ADG84, FCR84, and RFI84). Based on single-step genomic best linear unbiased prediction, three BW traits and two ADG traits had the high estimates (±standard error, SE) of heritability, ranging from 0.44 ± 0.13 of BW35 to 0.66 ± 0.08 of BW70. Moderate heritabilities were observed for RFI70 (0.22 ± 0.07) and RFI84 (0.29 ± 0.07), whereas the estimates did not significantly deviate from zero for the two FCR traits. There was moderate positive genetic correlation (±SE) between BW70 and ADG70 (0.579 ± 0.086), but BW70 did not correlate with RFI70. Based on microbial best linear unbiased prediction, the estimates of microbiability did not significantly deviate from zero for any trait. Based on the combined use of genomic and gut microbiota data, the parameters obtained in this study could help us to implement efficient breeding schemes in meat rabbits.

The aim of this study was to examine the influence of daily contact features on the prevalence of common mental disorders (CMDs) in Taiwan from 2000 to 2015. Data from the Taiwan Social Change Survey for 2000, 2005, 2010, and 2015 were used to examine the relationship between the number and level of familiarity with daily social contacts with the probable CMDs (determined by score of ≥ 3 on a 12-item Chinese Health Questionnaire). Descriptive statistics and multivariable logistic regression analyses were used to assess the association. Among the 7,841 respondents, the prevalence of probable CMDs increased from 18.28% in 2000 to 21.29% in 2015. Multivariable analysis showed that respondents with more daily social contacts were less likely to have probable CMDs in the four observed years adjusting for sociodemographic characteristics and physical health limitations on daily activities in the past two weeks. A negative relationship between probable CMDs and level of familiarity with daily contacts was found in 2000 (OR = 0.67, 95% CI-0.48-0.94) and 2005 (OR = 0.70, 95% CI-0.53-0.93). Findings from our study suggest the development of culturally tailored programs/interventions through features of daily social contacts may reduce the prevalence of CMDs in Taiwan., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The transjugular intrahepatic portosystemic shunt (TIPS) is an important technique for treating complications related to portal hypertension in patients with cirrhosis, and the number of publications in the TIPS field continues to rise., Aim: To facilitate an understanding of the research status and hotspots in the field of TIPS using CiteSpace bibliometric analysis., Methods: CiteSpace is a software that depicts the strength of relationships through graphics and connections with diverse functionalities and can be used to analyze the status and hotspots of areas of research. Articles on TIPS in the Web of Science Core Collection were retrieved, and CiteSpace software was used to visualize and analyze the number of publications, journals, countries, institutions, authors, keywords, and citations., Results: A total of 985 relevant documents were included in the analysis. From January 2013 to December 2022, the number of publications increased annually. The journal, institution, and author with the greatest number of publications in the field of TIPS are the Journal of Vascular and Interventional Radiology , the University of Bonn, and Jonel Trebicka, respectively. The main keywords used in this field are "transjugular intrahepatic portosystemic shunt", "portal hypertension", "cirrhosis", "management", "stent", "hepatic encephalopathy", "refractory ascite", "survival", "risk", and "variceal bleeding". The greatest obstacle to TIPS placement is currently the occurrence of hepatic encephalopathy. The research hotspots are the mechanism, risk factors, management, and control of hepatic encephalopathy., Conclusion: This bibliometric analysis reported the research status and hotspots of TIPS. Research on postoperative hepatic encephalopathy is the research hotspot in this field., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Staphylococcus aureus ( S. aureus ) is a major global health concern, causing various infections and presenting challenges due to antibiotic resistance. In particular, methicillin-resistant S. aureus , vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus pose significant obstacles in treating S. aureus infections. Therefore, the critical need for novel drugs to counter these resistant forms is pressing. Two-component systems (TCSs), integral to bacterial regulation, offer promising targets for disruption. In this study, a comprehensive approach, involving pharmacophore-based inhibitor screening, along with biochemical and biophysical analyses were conducted to identify, characterize, and validate potential inhibitors targeting the response regulator VraRC of S. aureus . The constructed pharmacophore model, Phar-VRPR-N3 , demonstrated effectiveness in identifying a potent inhibitor, TST1N-224 (IC 50 = 60.2 ± 4.0 μM), against the formation of the VraRC-DNA complex. Notably, TST1N-224 exhibited strong binding to VraRC (KD = 23.4 ± 1.2 μM) using a fast-on-fast-off binding mechanism. Additionally, NMR-based molecular modeling revealed that TST1N-224 predominantly interacts with the α9- and α10-helixes of the DNA-binding domain of VraR, where the interactive and functionally essential residues (N165, K180, S184, and R195) act as hotspots for structure-based inhibitor optimization. Furthermore, TST1N-224 evidently enhanced the susceptibility of VISA to both vancomycin and methicillin. Importantly, TST1N-224 distinguished by 1,2,5,6-tetrathiocane with the 3 and 8 positions modified with ethanesulfonates holds significant potential as a lead compound for the development of new antimicrobial agents.

In recent years, the incidence and mortality rates of cardiovascular diseases in China have kept rising, with no significant reduction in disease burden observed. Percutaneous coronary intervention(PCI) is an effective approach for treating coronary artery disease. Drug-eluting stents and drug-coated balloons are currently the most common PCI devices used in clinical practice. However, challenges with restenosis and late-stage thrombotic events persist. Inhibiting the proliferation of vascular smooth muscle cells while enhancing endothelial cell activity is crucial for reducing restenosis and preventing thrombosis, and it remains a challenge in research. The active compounds and extracts of traditional Chinese medicine(TCM), particularly the combinations of active compounds in coatings, possess multi-target potential and serve as a supplement to coatings prepared from synthetic compounds. This review elucidates the application of TCM active compounds(such as arsenic trioxide, paclitaxel, hirudin, tetramethylpyrazine, emodin, oxymatrine, and curcumin), combinations of TCM active compounds(paclitaxel/hirudin, geniposide/baicalin), and TCM extracts(such as Curcumae Rhizoma extract and Tripterygium hypoglaucum extract) in the coatings for PCI devices in recent years. Furthermore, this review expounds the current challenges and future prospects in this field, giving insights into the innovation of PCI devices.

Background: Yaks are a vital livestock in the Qinghai-Tibetan Plateau area for providing food products, maintaining sustainable ecosystems, and promoting cultural heritage. Because of uncontrolled mating, it is impossible to estimate inbreeding level of yak populations using the pedigree-based approaches. With the aims to accurately evaluate inbreeding level of two Chinese yak populations (Maiwa and Jiulong), we obtained genome-wide single nucleotide polymorphisms (SNPs) by DNA sequencing and calculated five SNP-by-SNP estimators ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]), as well as two segment-based estimators of runs of homozygosity (ROH, [Formula: see text]) and homozygous-by-descent (HBD, [Formula: see text]). Functional implications were analyzed for the positional candidate genes located within the related genomic regions., Results: A total of 151,675 and 190,955 high-quality SNPs were obtained from 71 Maiwa and 30 Jiulong yaks, respectively. Jiulong had greater genetic diversity than Maiwa in terms of allele frequency and nucleotide diversity. The two populations could be genetically distinguished by principal component analysis, with the mean differentiation index (Fst) of 0.0054. The greater genomic inbreeding levels of Maiwa yaks were consistently supported by all five SNP-by-SNP estimators. Based on simple proportion of homozygous SNPs ([Formula: see text]), a lower inbreeding level was indicated by three successfully sequenced old leather samples that may represent historical Maiwa yaks about five generations ago. There were 3304 ROH detected among all samples, with mean and median length of 1.97 Mb and 1.0 Mb, respectively. A total of 94 HBD segments were found among all samples, whereas 92 of them belonged to the shortest class with the mean length of 10.9 Kb. Based on the estimates of [Formula: see text] and [Formula: see text], however, there was no difference in inbreeding level between Maiwa and Jiulong yaks. Within the genomic regions with the significant Fst or enriched by ROH, we found several candidate genes and pathways that have been reported to be related to diverse production traits in farm animals., Conclusions: We successfully evaluated the genomic inbreeding level of two Chinese yak populations. Although different estimators resulted in inconsistent conclusions on their genomic inbreeding levels, our results may be helpful to implement the genetic conservation and utilization programs for the two yak populations., (© 2024. The Author(s).)

Taiwan is situated in the subtropical region and its geographical location and topographical features contribute to a rich ecological diversity and scenic landscapes. We investigated the diversity of methanogens in different environments of Taiwan using a culture-dependent method. This report presents the characterization and taxonomy of six hydrogenotrophic methanogens obtained from cold seep sediments (strain FWC-SCC1 T and FWC-SCC3 T ), marine sediments (strain CWC-02 T and YWC-01 T ), estuarine sediments (strain Afa-1 T ), and a hot spring well (strain Wushi-C6 T ) in Taiwan. The proposed names of the six novel species are Methanoculleus frigidifontis (type strain FWC-SCC1 T =BCRC AR10056 T =NBRC 113993 T ), Methanoculleus oceani (CWC-02 T =BCRC AR10055 T =NBRC 113992 T ), Methanoculleus methanifontis (FWC-SCC3 T =BCRC AR10057 T =NBRC 113994 T ), Methanoculleus nereidis (YWC-01 T =BCRC AR10060 T =NBRC 114597 T ), Methanoculleus formosensis (Afa-1 T =BCRC AR10054 T =NBRC 113995 T ), and Methanoculleus caldifontis (Wushi-06 T =BCRC AR10059 T = NBRC 114596 T ).

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP-DNA complex: ST132 (IC 50 = 29 ± 1.6 µM) and ST166 (IC 50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 μM) and ST132 (KD = 14.5 ± 0.1 μM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal β-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum . Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria., Competing Interests: There are no conflicts of interest to declare., (© 2024 The Authors.)

A novel mesophilic, hydrogenotrophic methanogen, strain CWC-04 T , was obtained from a sediment sample extracted from a gravity core retrieved at station 22 within the KP-9 area off the southwestern coast of Taiwan during the ORIII-1368 cruise in 2009. Cells of strain CWC-04 T were rod-shaped, 1.4-2.9 µm long by 0.5-0.6 µm wide, and occurred singly. Strain CWC-04 T utilized formate, H 2 /CO 2 , 2-propanol/CO 2 or 2-butanol/CO 2 as catabolic substrates. The optimal growth conditions were 42 °C, 0.17 M NaCl and pH 5.35. The genomic DNA G+C content calculated from the genome sequence of strain CWC-04 T was 46.19 mol%. Phylogenetic analysis of 16S rRNA gene revealed that strain CWC-04 T is affiliated with the genus Methanocella . The 16S rRNA gene sequences similarities within strains Methanocella arvoryzae MRE50 T , Methanocella paludicola SANAE T and Methanocella conradii HZ254 T were 93.7, 93.0 and 91.3 %, respectively. In addition, the optical density of CWC-04 T culture dropped abruptly upon entering the late-log growth phase, with virus-like particles (150 nm in diameter) being observed on and around the cells. This observation suggests that strain CWC-04 T harbours a lytic virus. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CWC-04 T represents a novel species of a novel genus in the family Methanocellaceae , for which the name Methanooceanicella nereidis gen. nov., sp. nov. is proposed. The type strain is CWC-04 T (=BCRC AR10050 T =NBRC 113165 T ).

High-density lipoprotein (HDL) cholesterol is a well-known biomarker, which has been associated with reduction in the risk of cardiovascular diseases (CVD). However, some HDL anti-atherosclerotic functions may be impaired without altered HDL-cholesterol (HDL-C) level via its dysfunctional proteins or other physiological reactions in vivo. We previously showed that activated mast cell-derived chymase could modestly cleave apolipoprotein A-I (apoA-I) in HDL 3, and further easily cleave lipid-free apoA-I. In contrast, myeloperoxidase (MPO) secreted by macrophages, the main cell type in atherosclerotic plaques, could oxidize HDL proteins, which might modify their tertiary structures, increasing their susceptibility to other enzymes. Here we focused on the co-modification and impact of chymase and MPO, usually secreted during inflammation from cells with possible co-existence in atheromas, on HDL. Only after sequential treatment with MPO and then chymase, two novel truncated apoA-I fragments were generated from HDL. One fragment was 16.5 kDa, and the cleavage site by chymase after MPO modification was the C-terminal of Tyr 100 in apoA-I, cross-validated by three different mass spectrometry methods. This novel apoA-I fragment can be trapped in HDL particles to avoid kidney glomerular filtration and has a specific site for antibody generation for ELISA tests. As such, its quantification can be useful in predicting patients with CVD having normal HDL-C levels., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Here, we report the complete genome sequence of Proteiniclasticum sp. QWL-01 (= BCRC 81396), isolated from sewage sludge of the Wastewater Treatment Plant of Sanming Steel Co. Ltd., Fujian, China. The genome of strain QWL-01 was selected for further species delineation and comparative genomic analysis., Competing Interests: The authors declare no conflict of interest.

Intelligent syndromic surveillance is an important part of multi-point triggering and multi-channel surveillance system of intelligent early warning of infectious diseases in China, and an inevitable development process of traditional syndromic surveillance as the constant emergence of new technologies. Intelligent syndromic surveillance collects not only the medical data of patients seeking medical care in hospitals but also massive non-medical information. However, along with its rapid development, challenges in intelligent syndromic surveillance have emerged, such as information explosion, cost-effective balance, information sharing, data security and privacy. This paper summarizes the concept and development of intelligent syndromic surveillance to provide references for the method and technique development of intelligent early warning of infectious diseases and new thought for the prevention and control of infectious diseases in China and in the world.

We report the complete genome sequence of Tissierella sp. strain Yu-01 (=BCRC 81391), isolated from the feces of black soldier fly (Hermetia illucens) larvae. This fly has increasingly been gaining attention because of its usefulness for recycling organic waste. The genome of strain Yu-01 was selected for further species delineation., Competing Interests: The authors declare no conflict of interest.

Acinetobacter baumannii is a nosocomial pathogen that can be resistant to antibiotics by rapidly modulating its anti-drug mechanisms. The multidrug-resistant A. baumannii has been considered one of the most threatening pathogens to our society. Biofilm formation and persistent cells within the biofilm matrix are recognized as intractable problems, especially in hospital-acquired infections. Poly-β-1,6-N-acetyl-glucosamine (PNAG) is one of the important building blocks in A. baumannii's biofilm. Here, we discover a protein phosphoryl-regulation on PNAG deacetylase, AbPgaB1, in which residue Ser411 was phosphorylated. The phosphoryl-regulation on AbPgaB1 modulates the product turnover rate in which deacetylated PNAG is produced and reflected in biofilm production. We further uncovered the PgaB deficient A. baumannii strain shows the lowest level of biofilm production but has a high minimal inhibition concentration to antibiotic colistin and tetracycline. Based on bactericidal post-antibiotic effects and time-dependent killing assays with antibacterial drugs, we claim that the PgaB-deficient A. baumannii converts to colistin-tolerant cells. This study utilizes a biofilm-independent colistin-tolerant model of A. baumannii to further investigate its characteristics and mechanisms to better understand clinical outcomes., (© 2023. The Author(s).)

Objectives: This study is aimed at exploring the feasibility of sonoelastography on muscle stiffness of spastic forearm and evaluating the improvement of functional performance in patients with poststroke spasticity (PSS) after receiving kinesiotaping (KT) and rehabilitation., Methods: According to the spastic levels (using modified Ashworth scale (MAS)) of the affected upper extremity, 59 patients with stroke were allocated into two groups, group A (MAS 0-1): 31 patients (14 men and 17 women; mean age: 60 years) and group B (MAS 1+-2): 28 patients (22 men and 6 women; mean age: 51 years). The Brunnstrom motor recovery stage at the wrist/distal parts in groups A and B was stage 3/3.5 and stage 2.75/3. We evaluated the Brunnstrom stage, spastic levels by MAS and modified Tardieu scale (MTS), and Fugl-Meyer Assessment for upper extremity (FMA-UE). We also evaluated the muscle spasticity of flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), and flexor digitorum superficialis (FDS) muscles using sonoelastography with shear wave velocity (SWV). We applied KT for 20 patients in group B, comparing the changes in sonoelastography and functional outcomes between KT and without KT interventions., Results: Both the MAS and MTS scales were moderately correlated with the SWV in forearm muscles on hemiplegic side ( r = 0.336-0.554) After KT intervention, the SWV in FCR decreased ( p = 0.028). Muscle spasticity was reduced ( p < 0.01), and distal part of the Brunnstrom stage and FMA-UE were increased ( p = 0.045 and p = 0.001). In patients without KT intervention, only the MTS degree reduced ( p = 0.026)., Conclusions: The SWV of sonoelastography could objectively assess the reduction of muscle stiffness of the affected forearms in patients with PSS after KT intervention. Advances in Knowledge . Sonoelastography could be a quantitative method to follow up for therapeutic effect of the spastic forearm., Competing Interests: There are no conflicts of interest to declare., (Copyright © 2023 Shih-Jung Lai et al.)

Purpose: Taiwan launched reimbursement of prophylactic coagulation factor replacement therapy (CFRT) for patients with severe hemophilia type A (severe PWHA) in 2014. However, since then, the effectiveness of prophylactic CFRT in real-world practice has not been evaluated thoroughly. This study aimed to evaluate the effectiveness of prophylactic CFRT in severe PWHA cases on the outcome of bleeding risks., Patients and Methods: We included male, severe PWHA cases from a nationwide, population-based database in Taiwan. Given that the database lacked details of the dosing regimen for prophylactic CFRT, we applied group-based trajectory modeling using the proportion of days covered (PDC) by CFRT from 2014 to 2015 in order to classify patients. A high PDC level corresponded to a greater proportion of time under CFRT, thus implying that the patient was probably receiving prophylactic therapy. We followed up patients from January 01, 2016 until occurrence of any bleeding events, death or December 31st 2017., Results: We identified a total of 420 severe PWHA and classified them into high- (n = 88), medium- (n = 181) and low- (n = 151) PDC groups. The mean (±SD) PDC values of the three groups were 0.78 (±0.1), 0.40 (±0.1) and 0.12 (±0.1), respectively. Using Cox regression models with propensity score adjustment, we found patients with medium- (hazard ratio: 0.69; 95% CI: 0.56-0.89) or high-PDC (0.45; 0.36-0.68) under CFRT had reduced risks of any bleeding, compared to the low PDC group., Conclusion: The findings demonstrated the effectiveness of prophylactic CFRT in the prevention of bleeding events in real-life severe PWHA., Competing Interests: The authors had received research funding from Takeda Pharmaceutical Company and Ministry of Science and Technology. However, the funders had no roles in study design, analysis or interpretation. The authors report no other conflicts of interest in this work., (© 2022 Hsieh et al.)

Background: The brown adipose tissue (BAT) is a target for treating obesity. BAT losses thermogenic capacity and gains a "white adipose tissue-like" phenotype ("BAT whitening") under thermoneutral environments, which is a potential factor causing a low curative effect in BAT-related obesity treatments. Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNA) to mRNAs and function in various processes by sponging shared microRNAs (miRNAs). However, the roles of circRNA- and lncRNA-related ceRNA networks in regulating BAT whitening remain litter known., Results: In this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). MiRNA-seq was performed to investigate miRNA changes during BAT whitening. Then, a combined analysis of circRNA-seq and whole-transcriptome sequencing was used for circRNA assembly and quantification during BAT whitening. Our data showed that 1187 miRNAs and 6204 circRNAs were expressed in the samples, and many of which were identified as significantly changed during BAT whitening. Target prediction showed that D0-selective miRNAs were significantly enriched in the Ras, MAPK, and PI3K-Akt signaling pathways, and Y2-selective miRNAs were predicted to be involved in cell proliferation. The cyclization of several circRNAs could form novel response elements of key thermogenesis miRNAs at the back-splicing junction (BSJ) sites, and in combination with a dual-luciferase reporter assay confirmed the binding between the BSJ site of novel&#95;circ&#95;0013792 and ocu-miR-378-5p. CircRNAs and lncRNAs have high cooperativity in sponging miRNAs during BAT whitening. Both circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA triple networks were significantly involved in immune response-associated biological processes. The D15-selective circRNA might promote BAT whitening by increasing the expression of IDH2. The Y2-selective circRNA-related ceRNA network and lncRNA-related ceRNA network might regulate the formation of the WAT-like phenotype of BAT via MAPK and Ras signaling pathways, respectively., Conclusions: Our work systematically revealed ceRNA networks during BAT whitening in rabbits and might provide new insight into BAT-based obesity treatments., (© 2022. The Author(s).)

Influenza is an acute respiratory infectious disease caused by influenza virus. It usually exhibits seasonal transmission, but the novel influenza strain can lead to a pandemic with severe human health and socioeconomic consequences. Early warning of influenza epidemic is an important strategy and means for influenza prevention and control. On the basis of reviewing the main influenza surveillance and early warning systems, this study summarizes the principles, applications, advantages and disadvantages, and development prospects of common influenza early warning models, in order to provide reference for research and application of early warning technology for influenza and other acute respiratory infectious diseases.

Bacterial capsular polysaccharides provide protection against environmental stress and immune evasion from the host immune system, and are therefore considered to be attractive therapeutic targets for the development of anti-infectious reagents. Here, we focused on CapG, one of the key enzymes in the synthesis pathway of capsular polysaccharides type 5 (CP5) from the opportunistic pathogen Staphylococcus aureus. SaCapG catalyses the 2-epimerization of UDP-N-acetyl-D-talosamine (UDP-TalNAc) to UDP-N-acetyl-D-fucosamine (UDP-FucNAc), which is one of the nucleotide-activated precursors for the synthesis of the trisaccharide repeating units of CP5. Here, the cloning, expression and purification of recombinant SaCapG are reported. After extensive efforts, single crystals of SaCapG were successfully obtained which belonged to space group C2 and exhibited unit-cell parameters a = 302.91, b = 84.34, c = 145.09 Å, β = 110.65°. The structure was solved by molecular replacement and was refined to 3.2 Å resolution. The asymmetric unit revealed a homohexameric assembly of SaCapG, which was consistent with gel-filtration analysis. Structural comparison with UDP-N-acetyl-D-glucosamine 2-epimerase from Methanocaldococcus jannaschii identified α2, the α2-α3 loop and α10 as a gate-regulated switch controlling substrate entry and/or product release.

The family Methanocalculaceae comprises hydrogen- and formate-utilizing methanogens. Here, we report two additional draft genome sequences of Methanocalculaceae , those of Methanocalculus taiwanensis P2F9704a T (equivalent to BCRC 16182 T and DSM 14663 T ) and Methanocalculus chunghsingensis K1F9705b T (equivalent to DSM 14646 T and OCM 772 T ), which were selected for further species delineation and comparative genomic analyses.

The hydrogenotrophic methanogen Methanofollis aquaemaris BCRC 16166 T (= N2F9704 T = DSM 14661 T ) was isolated from a marine aquaculture fishpond near Wang-gong (Taiwan, Republic of China). The genome of strain BCRC 16166 T was selected for sequencing in order to provide further information about the species delineation and its infected virus.

Brown adipose tissue (BAT) represents a valuable target for treating obesity in humans. BAT losses of thermogenic capacity and gains a "white adipose tissue-like (WAT-like)" phenotype (BAT whitening) under thermoneutral environments, which could lead to potential low therapy responsiveness in BAT-based obesity treatments. However, the epigenetic mechanisms of BAT whitening remain largely unknown. In this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). RNA-sequencing (RNA-seq) and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were performed to investigate transcriptome and chromatin accessibility of BATs at the four whitening stages, respectively. Our data showed that many genes and chromatin accessible regions (refer to as "peaks") were identified as significantly changed during BAT whitening in rabbits. The BAT-selective genes downregulated while WAT-selective genes upregulated from D0 to Y2, and the de novo lipogenesis-related genes reached the highest expression levels at D85. Both the highly expressed genes and accessible regions in Y2 were significantly enriched in immune response-related signal pathways. Analysis of different relationships between peaks and their nearby genes found an increased proportion of the synchronous changes between chromatin accessibility and gene expression during BAT whitening. The synergistic changes between the chromatin accessibility of promoter and the gene expression were found in the key adipose genes. The upregulated genes which contained increased peaks were significantly enriched in the PI3K-Akt signaling pathway, steroid biosynthesis, TGF-beta signaling pathway, osteoclast differentiation, and dilated cardiomyopathy. Moreover, the footprinting analysis suggested that sequential regulation of potential transcription factors (TFs) mediated the loss of thermogenic phenotype and the gain of a WAT-like phenotype of BAT. In conclusion, our study provided the transcriptional and epigenetic frameworks for understanding BAT whitening in rabbits for the first time and might facilitate potential insights into BAT-based obesity treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Chen, Bai, Chen, Hu, Li, Wang, He and Lai.)

Eggshell membrane (ESM), a plentiful biological waste, consists of collagen-like proteins and glycosaminoglycans (GAGs) such as hyaluronic acid (HA). Here we used a keratinase (oeMtaker)-mediated system to decompose ESM. The best reaction condition was established by incubating the solution containing oeMtaker, sodium sulfite, and ESM with a weight ratio of 1:120:600. ESM enzymatic hydrolysate (ESM-EH) showed a high proportion of essential amino acids and type X collagen peptides with 963-2259 Da molecular weights. The amounts of GAGs and sulfated GAGs in ESM-EH were quantified as 6.4% and 0.7%, respectively. The precipitated polysaccharides with an average molecular weight of 1300-1700 kDa showed an immunomodulatory activity by stimulating pro-inflammatory cytokines (IL-6 and TNF-α) production. In addition, a microorganism-based system was established to hydrolyze ESM by Meiothermus taiwanensis WR-220. The amounts of GAGs and sulfated GAGs in the system were quantified as 0.9% and 0.1%, respectively. Based on our pre-pilot tests, the system shows great promise in developing into a low-cost and high-performance process. These results indicate that the keratinase-mediated system could hydrolyze ESM more efficiently and produce more bioactive substances than ever for therapeutical applications and dietary supplements., (© 2022. The Author(s).)

Both cis - and trans -regulation could cause differential expression between the parental alleles in diploid species that might have broad biological implications. Due to the relatively distant genetic divergence between cattle and yak, as well as their differential adaptation to high-altitude environments, we investigated genome-wide allelic differential expression (ADE) in their F1 hybrids using Nanopore long-read RNA-seq technology. From adult F1 hybrids raised in high-altitude, ten lung and liver tissues were individually sequenced for producing 31.6 M full-length transcript sequences. Mapping against autosomal homologous regions between cattle and yak, we detected 17,744 and 14,542 protein-encoding genes expressed in lung and liver tissues, respectively. According to the parental assignments of transcript sequences, a total of 3,381 genes were detected to show ADE in at least one sample. There were 186 genes showing ubiquitous ADE in all the studied animals, and among them 135 and 37 genes had consistent higher expression of yak and cattle alleles, respectively. Functional analyses revealed that the genes with favoring expression of yak alleles have been involved in the biological progresses related with hypoxia adaptation and immune response. In contrast, the genes with favoring expression of cattle alleles have been enriched into different biological progresses, such as secretion of endocrine hormones and lipid metabolism. Our results would support unequal contribution of parental genes to environmental adaptation in the F1 hybrids of cattle and yak., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Li, Luo, Li, Jia and Lai.)

Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (M pro ), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV M pro and can thermodynamically stabilize its folding. The structure of CCoV M pro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV M pro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV M pro and other animal CoV M pro s with SARS-CoV-2 M pro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral M pro s, SARS-CoV-2 M pro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46-49 in animal coronaviral M pro s has been replaced by a stable α-helix in SARS-CoV-2 M pro . In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV M pro s. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV M pro s among different species.

The COVID-19 pandemic resulting from the spread of SARS-CoV-2 spurred devastating health and economic crises around the world. Neutralizing antibodies and licensed vaccines were developed to combat COVID-19, but progress was slow. In addition, variants of the receptor-binding domain (RBD) of the spike protein confer resistance of SARS-CoV-2 to neutralizing antibodies, nullifying the possibility of human immunity. Therefore, investigations into the RBD mutations that disrupt neutralization through convalescent antibodies are urgently required. In this study, we comprehensively and systematically investigated the binding stability of RBD variants targeting convalescent antibodies and revealed that the RBD residues F456, F490, L452, L455, and K417 are immune-escaping hotspots, and E484, F486, and N501 are destabilizing residues. Our study also explored the possible modes of actions of emerging SARS-CoV-2 variants. All results are consistent with experimental observations of attenuated antibody neutralization and clinically emerging SARS-CoV-2 variants. We identified possible immune-escaping hotspots that could further promote resistance to convalescent antibodies. The results provide valuable information for developing and designing novel monoclonal antibody drugs to combat emerging SARS-CoV-2 variants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fung, Lai, Lin and Tseng.)

Objectives: Cholesterol efflux capacity (CEC), an atheroprotective function of high-density lipoprotein, is expected to be a potential biomarker for cardiovascular disease. However, CEC has not been widely introduced for application in clinical laboratories because of the complexity of the conventional CEC assay using cells and radioactive materials. Previously, we developed a novel CEC assay using immobilized liposome-bound gel beads (ILG), which solves these issues. We aimed to confirm the validation and further improve the ILG method for application in the clinical setting., Methods: Cholesterol efflux capacity values by the ILG method assayed for shorter incubation time (4 h) were compared to those assayed for 16 h (our previous ILG method). To investigate a reference material that can correct the variation between ILG manufacturing lots, bovine serum albumin, human gamma-globulins, and globulin complexes were evaluated. CEC values were also estimated in plasmas obtained with different anticoagulants, serum treated with freeze-thaw cycles, and serum mixed with several interference substances., Results: The CEC of 4- and 16-h incubation times were well correlated. Globulin complexes may be used as a reference material. Plasma can be used as the specimen. The serum and stored temperature of the specimen did not largely affect CEC. Hemoglobin and chyle did not have an effect on CEC, whereas high-bilirubin serum showed elevated CEC. The effect of bilirubin was nearly canceled by subtracting basal fluorescence intensity., Conclusions: Present ILG method further fulfills some requirements for application in clinical laboratory. Using this reliable simple method, evaluation for clinical significance of CEC is expected.

Background: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China., Methods: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods., Findings: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased., Interpretation: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy., Funding: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds., Competing Interests: We declare no competing interests., (© 2021 The Author(s).)

Liangshan cattle are a very small indigenous breed with adult weight of less than 300 Kg and have been mainly distributed in the Liangshan Yi Autonomous Prefecture of Southwestern Sichuan, China. Due to its long-term adaptation to local environments, Liangshan cattle is a valuable genetic resource and should be paid with more attentions. However, the genetic diversity of Liangshan cattle have not been specifically investigated yet, which would be required when designing the appropriate conservation and utilization programs. In this study, we successfully employed the restriction-site-associated DNA sequencing (RAD-seq) approach to explore a total of 84,854 genome-wide and high-confidence SNPs of Liangshan cattle. All these SNPs were evenly distributed through all chromosomes with an average of 98 SNPs per 1-Mb region. The nucleotide diversity, expected heterozygosity, polymorphism information content of Liangshan cattle were 0.227, 0.223 and 0.183, respectively. Furthermore, there was no obvious difference on the genetic diversity among the three studied geographical populations. In conclusion, we provided a list of SNPs that could be used in the follow-up studies for Liangshan cattle and revealed a relatively high genetic variation in this gene pool.

The active ingredients of Ficus hirta and Hypericum perforatum were collected from Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and related papers. The potential targets of these two medicinal herbs were searched from HERB database, and those associated with microvascular angina were screened out from GeneCards, Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), and HERB. Cytoscape was used to construct a protein-protein interaction(PPI) network of the common targets shared by the two herbs and microvascular angina based on the data of String platform. Metascape was employed to identify the involved biological processes and pathways enriched with the common targets. Cytoscape was used to draw the &quot;active ingredient-target-pathway&quot; network. AutoDock Vina was used to dock the core ingredients with the key targets. A total of 19 potential active ingredients and 71 potential targets were identified to be associated with microvascular angina. Bioinformatics analysis showed that phosphatidylinositol-3-kinase/protein kinase B(PI3 K-AKT), interleukin-17(IL17), hypoxia-inducible factor 1(HIF-1) and other signaling pathways were related to the treatment of microvascular angina by F. hirta and H. perforatum. Molecular docking results showed that β-sitosterol, luteolin and other ingredients had strong affinity with multiple targets including mitogen-associated protein kinase 1(MAPK1), epidermal growth factor receptor(EGFR) and so on. These findings indicated that F. hirta and H. perforatum may regulate PI3 K-AKT, IL17, HIF-1 and other signaling pathways by acting on multiple targets to alleviate oxidative stress, inhibit inflammatory response, regulate angiogenesis, and improve vascular endothelium and other functions. This study provides reference for in vitro and in vivo studies of the treatment of microvascular angina.

Non-contact physiological measurements based on image sensors have developed rapidly in recent years. Among them, thermal cameras have the advantage of measuring temperature in the environment without light and have potential to develop physiological measurement applications. Various studies have used thermal camera to measure the physiological signals such as respiratory rate, heart rate, and body temperature. In this paper, we provided a general overview of the existing studies by examining the physiological signals of measurement, the used platforms, the thermal camera models and specifications, the use of camera fusion, the image and signal processing step (including the algorithms and tools used), and the performance evaluation. The advantages and challenges of thermal camera-based physiological measurement were also discussed. Several suggestions and prospects such as healthcare applications, machine learning, multi-parameter, and image fusion, have been proposed to improve the physiological measurement of thermal camera in the future.

Growth is a complex trait with moderate to high heritability in livestock and must be described by the longitudinal data measured over multiple time points. Therefore, the used phenotype in genome-wide association studies (GWAS) of growth traits could be either the measures at the preselected time point or the fitted parameters of whole growth trajectory. A promising alternative approach was recently proposed that combined the fitting of growth curves and estimation of single-nucleotide polymorphism (SNP) effects into single-step nonlinear mixed model (NMM). In this study, we collected the body weights at 35, 42, 49, 56, 63, 70, and 84 days of age for 401 animals in a crossbred population of meat rabbits and compared five fitting models of growth curves (Logistic, Gompertz, Brody, Von Bertalanffy, and Richards). The logistic model was preferably selected and subjected to GWAS using the approach of single-step NMM, which was based on 87,704 genome-wide SNPs. A total of 45 significant SNPs distributed on five chromosomes were found to simultaneously affect the two growth parameters of mature weight (A) and maturity rate (K). However, no SNP was found to be independently associated with either A or K. Seven positional genes, including KCNIP4 , GBA3 , PPARGC1A , LDB2 , SHISA3 , GNA13 , and FGF10 , were suggested to be candidates affecting growth performances in meat rabbits. To the best of our knowledge, this is the first report of GWAS based on single-step NMM for longitudinal traits in rabbits, which also revealed the genetic architecture of growth traits that are helpful in implementing genome selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liao, Wang, Glória, Zhang, Zhang, Yang, Luo, Jia, Lai and Chen.)

Endothelial cell (EC) migration is essential for healing vascular injuries. Previous studies suggest that high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I), the major protein constituent of HDL, have endothelial healing functions. In cardiovascular disease, HDL is modified by myeloperoxidase (MPO) and N -homocysteine, resulting in apoA-I/apoA-II heterodimer and N -homocysteinylated ( N -Hcy) apoA-I formation. This study investigated whether these modifications attenuate HDL-mediated endothelial healing. Wound healing assays were performed to analyze the effect of MPO-oxidized HDL and N -Hcy HDL in vitro . HDL obtained from patients with varying troponin I levels were also examined. MPO-oxidized HDL reduces EC migration compared to normal HDL in vitro , and N -Hcy HDL showed a decreasing trend toward EC migration. EC migration after treatment with HDL from patients was decreased compared to HDL isolated from healthy controls. Increased apoA-I/apoA-II heterodimer and N -Hcy apoA-I levels were also detected in HDL from patients. Wound healing cell migration was significantly negatively correlated with the ratio of apoA-I/apoA-II heterodimer to total apoA-II and N -Hcy apoA-I to total apoA-I. MPO-oxidized HDL containing apoA-I/apoA-II heterodimers had a weaker endothelial healing function than did normal HDL. These results indicate that MPO-oxidized HDL and N -Hcy HDL play a key role in the pathogenesis of cardiovascular disease., (© 2022 Takahiro Kameda et al., published by De Gruyter, Berlin/Boston.)

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China., (© 2021. The Author(s).)

This paper summarizes the basic principles and models of early warning for infectious disease outbreaks, introduces the early warning systems for infectious disease based on different data sources and their applications, and discusses the application potential of big data and their analysing techniques, which have been studied and used in the prevention and control of COVID-19 pandemic, including internet inquiry, social media, mobile positioning, in the early warning of infectious diseases in order to provide reference for the establishment of an intelligent early warning mechanism and platform for infectious diseases based on multi-source big data.

Triglyceride hydrolysis by lipoprotein lipase (LPL), regulated by apolipoproteins C-II (apoC-II) and C-III (apoC-III), is essential for maintaining normal lipid homeostasis. During triglyceride lipolysis, the apoCs are known to be transferred from very low-density lipoprotein (VLDL) to high-density lipoprotein (HDL), but the detailed mechanisms of this transfer remain unclear. In this study, we investigated the extent of the apoC transfers and their distribution in HDL subfractions, HDL2 and HDL3. Each HDL subfraction was incubated with VLDL or biotin-labeled VLDL, and apolipoproteins and lipids in the re-isolated HDL were quantified using western blotting and high-performance liquid chromatography (HPLC). In consequence, incubation with VLDL showed the increase of net amount of apoC-II and apoC-III in the HDL. HPLC analysis revealed that the biotin-labeled apolipoproteins, including apoCs and apolipoprotein E, were preferably transferred to the larger HDL3. No effect of cholesteryl ester transfer protein inhibitor on the apoC transfers was observed. Quantification of apoCs levels in HDL2 and HDL3 from healthy subjects (n = 8) showed large individual differences between apoC-II and apoC-III levels. These results suggest that both apoC-II and apoC-III transfer disproportionately from VLDL to HDL2 and the larger HDL3, and these transfers might be involved in individual triglyceride metabolism., Competing Interests: The authors declare no conflicts of interest regarding this article.

Background: A local coronavirus disease 2019 (COVID-19) case confirmed on June 11, 2020 triggered an outbreak in Beijing, China after 56 consecutive days without a newly confirmed case. Non-pharmaceutical interventions (NPIs) were used to contain the source in Xinfadi (XFD) market. To rapidly control the outbreak, both traditional and newly introduced NPIs including large-scale management of high-risk populations and expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-based screening in the general population were conducted in Beijing. We aimed to assess the effectiveness of the response to the COVID-19 outbreak in Beijing's XFD market and inform future response efforts of resurgence across regions., Methods: A modified susceptible-exposed-infectious-recovered (SEIR) model was developed and applied to evaluate a range of different scenarios from the public health perspective. Two outcomes were measured: magnitude of transmission (i.e., number of cases in the outbreak) and endpoint of transmission (i.e., date of containment). The outcomes of scenario evaluations were presented relative to the reality case (i.e., 368 cases in 34 days) with 95% Confidence Interval (CI)., Results: Our results indicated that a 3 to 14 day delay in the identification of XFD as the infection source and initiation of NPIs would have caused a 3 to 28-fold increase in total case number (31-77 day delay in containment). A failure to implement the quarantine scheme employed in the XFD outbreak for defined key population would have caused a fivefold greater number of cases (73 day delay in containment). Similarly, failure to implement the quarantine plan executed in the XFD outbreak for close contacts would have caused twofold greater transmission (44 day delay in containment). Finally, failure to implement expanded nucleic acid screening in the general population would have yielded 1.6-fold greater transmission and a 32 day delay to containment., Conclusions: This study informs new evidence that in form the selection of NPI to use as countermeasures in response to a COVID-19 outbreak and optimal timing of their implementation. The evidence provided by this study should inform responses to future outbreaks of COVID-19 and future infectious disease outbreak preparedness efforts in China and elsewhere.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

Meleagrin B is a terpene-alkaloid hybrid natural product that contains both the conidiogenone and meleagrin scaffold. Their derivatives show diverse biological activities. We characterized the biosynthesis of (-)-conidiogenone B ( 1 ), which involves a diterpene synthase and a P450 monooxygenase. In addition, an α,β-hydrolase (Con-ABH) was shown to catalyze an aza-Michael addition between 1 and imidazole to give 3S -imidazolyl conidiogenone B ( 6 ). Compound 6 was more potent than 1 against Staphylococcus aureus strains.

High-density lipoprotein- (HDL-) cholesterol measurements are generally used in the diagnosis of cardiovascular diseases. However, HDL is a complicated heterogeneous lipoprotein, and furthermore, it can be converted into dysfunctional forms during pathological conditions including inflammation. Therefore, qualitative analysis of pathophysiologically diversified HDL forms is important. A recent study demonstrated that serum amyloid A (SAA) can remodel HDL and induce atherosclerosis not only over long periods of time, such as during chronic inflammation, but also over shorter periods. However, few studies have investigated rapid HDL remodeling. In this study, we analyzed HDL samples from patients undergoing orthopedic surgery inducing acute inflammation. We enrolled 13 otherwise healthy patients who underwent orthopedic surgery. Plasma samples were obtained on preoperative day and postoperative days (POD) 1-7. SAA, apolipoprotein A-I (apoA-I), and apolipoprotein A-II (apoA-II) levels in the isolated HDL were determined. HDL particle size, surface charge, and SAA and apoA-I distributions were also analyzed. In every patient, plasma SAA levels peaked on POD3. Consistently, the HDL apoA-I : apoA-II ratio markedly decreased at this timepoint. Native-polyacrylamide gel electrophoresis and high-performance liquid chromatography revealed the loss of small HDL particles during acute inflammation. Furthermore, HDL had a decreased negative surface charge on POD3 compared to the other timepoints. All changes observed were SAA-dependent. SAA-dependent rapid changes in HDL size and surface charge were observed after orthopedic surgery. These changes might affect the atheroprotective functions of HDL, and its analysis can be available for the qualitative HDL assessment., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 Shitsuko Shimano et al.)

Ketosis is a common metabolic disease in dairy cows during early lactation. However, information about the metabolomic and proteomic profiles associated with the incidence and progression of ketosis is still limited. In this study, an integrated metabolomics and proteomics approach was performed on blood serum sampled from cows diagnosed with clinical ketosis (case, ≥ 2.60 mmol/L plasma β-hydroxybutyrate; BHBA) and healthy controls (control, < 1.0 mmol/L BHBA). Samples were taken 2 weeks before parturition and 2 weeks after parturition from 19 animals (nine cases, 10 controls). All serum samples ( n = 38) were subjected to Liquid Chromatography-Mass Spectrometry (LC-MS) based metabolomic analysis, and 20 samples underwent Data-Independent Acquisition (DIA) LC-MS based proteomic analysis. A total of 97 metabolites and 540 proteins were successfully identified, and multivariate analysis revealed significant differences in both metabolomic and proteomic profiles between cases and controls. We investigated clinical ketosis-associated metabolomic and proteomic changes using statistical analyses. Correlation analysis of statistically significant metabolites and proteins showed 78 strong correlations (correlation coefficient, R ≥ 0.7) between 38 metabolites and 25 proteins, which were then mapped to pathways using IMPaLA. Results showed that ketosis altered a wide range of metabolic pathways, such as metabolism, metabolism of proteins, gene expression and post-translational protein modification, vitamin metabolism, signaling, and disease related pathways. Findings presented here are relevant for identifying molecular targets for ketosis and biomarkers for ketosis detection during the transition period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wu, Chen, Hu, Jia, Wang and Lai.)

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1 +/+ and Abca1 -/- mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article.

Acinetobacter baumannii is a prevalent pathogen that can rapidly acquire resistance to antibiotics. Indeed, multidrug-resistant A. baumannii is a major cause of hospital-acquired infections and has been recognised by the World Health Organization as one of the most threatening bacteria to our society. Resistance-nodulation-division (RND) type multidrug efflux pumps have been demonstrated to convey antibiotic resistance to a wide range of pathogens and are the primary resistance mechanism employed by A. baumannii. A component of an RND pump in A. baumannii, AdeT1, was previously demonstrated to enhance the antimicrobial resistance of Escherichia coli. Here, we report the results of experiments which demonstrate that wild-type AdeT1 does not confer antimicrobial resistance in E. coli, highlighting the importance of verifying protein production when determining minimum inhibitory concentrations (MICs) especially by broth dilution. Nevertheless, using an agar-based MIC assay, we found that propionylation of Lys280 on AdeT1 renders E. coli cells more resistant to erythromycin.

This paper reviews the limitations of current infectious disease surveillance and early warning system in China, analyzes the concepts and countermeasures of the establishment of an intelligent early warning platform of infectious diseases based on multi-point trigger mechanism and multi-channel surveillance mechanism and proposes the realization routes for the purpose of facilitating capacity building and improvement of surveillance and early warning of infectious diseases in China.

Background and Objective: Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice., Methods: Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively., Results: A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition., Conclusions: In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.