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Abstract The management of papillary thyroid carcinoma (PTC) concurrent with Hashimoto’s thyroiditis (HT) lacks standardized guidelines, especially concerning surgical strategies. This study aimed to compare unilateral thyroidectomy (UT) with total thyroidectomy (TT) in PTC-HT patients to optimize clinical management and improve postoperative outcomes. This retrospective study included PTC-HT patients undergoing thyroid surgery at a tertiary academic medical institution from January 2018 to August 2023. The patients were grouped according to the quartiles of preoperative thyroid peroxidase antibody (TPOAB) levels at the last follow-up. Additionally, patients were divided into UT and TT groups, with propensity score matching (PSM) to ensure comparability. Patients were also stratified by TPOAB levels (L: 100–400, M: 400–1000, H: >1000). Patient-reported outcomes (PROMs), including quality of life and fatigue, were compared between UT and TT groups within each TPOAB subgroup (ΔPROMs = UT-TT). 246 patients were included. Those with higher TPOAB levels at the last follow-up reported increased physical fatigue scores. After PSM, there were no significant demographic differences between UT and TT groups. During a median follow-up of 16 months for UT and 20 months for TT, no recurrence or metastasis occurred. Compared to the UT group, the TT group exhibited lower TPOAB levels at the last follow-up (65.7 ± 78 vs. 374.6 ± 331.9, p

Abstract Youth soccer specialty schools are the primary project to strengthen the foundation of soccer talents, improve the level of soccer development, and achieve the dream of Chinese soccer. Taking 32,775 soccer specialty schools in China as the research sample, ArcGIS spatial analysis technology is used to explore the spatial distribution characteristics of soccer specialty schools and their influencing factors. The analysis shows that the overall distribution of the country forms five quantity concentration area and eight high-density core areas, with a high degree of spatial concentration and significant differences between the East and West. The factors influencing soccer specialty schools include nine factors in four dimensions: historical development, geographical environment, socio-economic, and educational resources. It was found that geographic environment and socio-economy provide the foundation and background for developing educational resources. However, the direct role of educational resources is more significant in a specific educational program, such as soccer specialty schools, followed by socio-economy and geographic environment. This study comprehensively analyzes and interprets soccer specialty schools’ spatial distribution characteristics and influencing factors. These results enrich the research on the spatial layout of sports, providing necessary theoretical support and practical references for the layout and high-quality development of related industries in China and other countries or regions.

Abstract Brucella spp. are facultative intracellular pathogens that cause zoonosis- brucellosis worldwide. There has been a trend of the re-emergence of brucellosis worldwide in recent years. The epidemic situation of brucellosis is serious in Xinjiang. To analyze the epidemic situation of Brucella spp. in Xinjiang among humans and animals, this study identified 144 Brucella isolates from Xinjiang using classical identification and 16 S rRNA sequencing. MLVA, drug resistance testing, and wgSNP detection were also performed. At the same time, analysis was conducted based on the published data of Brucella isolates worldwide. The results showed that the dominant species was B. melitensis biovar 3, which belonged to GT42 (MLVA-8 typing) and the East Mediterranean lineage. The correlation among isolates was high both in humans or animals. The isolates in Xinjiang exhibited higher polymorphism compared to other locations in China, with polymorphism increasing each year since 2010. No amikacin/kanamycin-resistant strains were detected, but six rifampicin-intermediate isolates were identified without rpoB gene variation. The NJ tree of the wgSNP results indicated that there were three main complexes of the B. melitensis epidemic in Xinjiang. Based on the results of this study, the prevention and control of brucellosis in Xinjiang should focus on B. melitensis, particularly strains belonging to B. melitensis bv.3 GT42 (MLVA-8 typing) and East Mediterranean lineage. Additionally, the rifampicin- and trimethoprim-sulfamethoxazole- resistance of isolates in Xinjiang should be closely monitored to avoid compromising the therapeutic efficacy and causing greater losses. These results provide essential data for the prevention and control of brucellosis in Xinjiang and China. Although the isolates from Xinjiang have significant characteristics among Chinese isolates and can reflect the epidemiological situation of brucellosis in China to some extent, this study cannot represent the characteristics of isolates from other regions.

Abstract There are no targeted rehabilitation training modalities and assessment tools for patients after transoral endoscopic thyroidectomy vestibular approach (TOETVA). Herein, we develop a new assessment questionnaire and rehabilitation training modality and evaluate its safety and effectiveness. The THYCA-QoL-TOETVA questionnaire was compiled, and reliability and validity analyses were performed. Patients were divided into the new rehabilitation training group (N) or the conventional rehabilitation training group (C), and 1:1 propensity score matching (PSM) was performed after administering questionnaires to patients in both groups. Cervical range of motion (CROM) data were also measured and collected for statistical analysis. The questionnaire used in this study showed good expert authority, coordination, internal consistency, and questionnaire reliability. A total of 476 patients were included after PSM, and the questionnaire results showed that recovery and quality of life were better in the N group than in the C group (124.55 ± 8.171 vs. 122.94 ± 8.366, p = 0.026). Analysis of cervical spine mobility showed that rehabilitation was better in the N group compared to the C group at postoperative one month (flexion: 1.762°, extension: 4.720°, left lateral bending: 3.912°, right lateral bending: 4.061°, left axial rotation: 5.180°, right axial rotation: 5.199°, p value all of these

Exercise and Physical Activity are important factors to improve the student's health and academic status. Student exercise should be continuously monitored to eliminate risk factors and health issues. The previous monitoring system faced difficulties while handling the vast amount of data obtained from multiple sensors because it was affected by uncertainty and noise issues. The research difficulties are addressed with the help of the Multi-Attribute Fuzzy Evaluation Model (MAFEM), which monitors student's health using sensor data. The MAFEM approach uses the fuzzy set and fuzzy logic to derive the relationship between the features. In addition, the method uses preprocessing, fuzzification, defuzzification and rule evaluation processes. These steps are adjusted according to the threshold value that maximizes the personalization and holistic assessment efficiency because the system uses multiple attributes. During the analysis, MM-Fit dataset information is utilized to evaluate the system efficiency in which the system ensures the minimum computation complexity $O\left ({{ r.m.n }}\right)$ and minimum latency value $\left ({{ \approx 70mAh }}\right)$ .. In addition, the accuracy metrics are also applied to evaluate the system's effectiveness, with 97.11% precision, 0.23 RMSE and 0.26 MSE values.

Abstract The process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.

The reactive power optimization of an active distribution network can effectively deal with the problem of voltage overflows at some nodes caused by the integration of a high proportion of distributed sources into the distribution network. Aiming to address the limitations in previous studies of dynamic reactive power optimization using the cluster partitioning method, a three-stage dynamic reactive power optimization decoupling strategy for active distribution networks considering carbon emissions is proposed in this paper. First, a carbon emission index is proposed based on the carbon emission intensity, and a dynamic reactive power optimization mathematical model of an active distribution network is established with the minimum active power network loss, voltage deviation, and carbon emissions as the satisfaction objective functions. Second, in order to satisfy the requirement for the all-day motion times of discrete devices, a three-stage dynamic reactive power optimization decoupling strategy based on the partitioning around a medoids clustering algorithm is proposed. Finally, taking the improved IEEE33 and PG&E69-node distribution network systems as examples, the proposed linear decreasing mutation particle swarm optimization algorithm was used to solve the mathematical model. The results show that all the indicators of the proposed strategy and algorithm throughout the day are lower than those of other methods, which verifies the effectiveness of the proposed strategy and algorithm.

BackgroundMounting evidence has demonstrated the associations between gut microbiota, gut microbiota-derived metabolites, and cerebrovascular diseases (CVDs). The major categories of CVD are ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). However, the causal relationship is still unclear.MethodsA two-sample Mendelian randomization (MR) study was conducted leveraging the summary data from genome-wide association studies. The inverse variance-weighted, maximum likelihood, weighted median, and MR.RAPS methods were performed to detect the causal relationship. Several sensitivity analyses were carried out to evaluate potential horizontal pleiotropy and heterogeneity. Finally, reverse MR analysis was conducted to examine the likelihood of reverse causality, and multivariable MR was performed to adjust the potential confounders.ResultsWe collected 1,505 host single nucleotide polymorphisms (SNPs) linked to 119 gut microbiota traits and 1,873 host SNPs associated with 81 gut metabolite traits as exposure data. Among these, three gut bacteria indicated an elevated risk of IS, two of ICH, and one of SAH. In contrast, five gut bacteria were associated with a reduced risk of IS, one with ICH, and one with SAH. Our study also demonstrated the potential causal associations between 11 gut microbiota-derived metabolites and CVD.ConclusionsThis study provided evidence of the causal relationship between gut microbiota, gut microbiota-derived metabolites, and CVD, thereby offering novel perspectives on gut biomarkers and targeted prevention and treatment for CVD.

As network technology advances, there is an increasing need for a trusted new-generation information management system. Blockchain technology provides a decentralized, transparent, and tamper-proof foundation. Meanwhile, data islands have become a significant obstacle for machine learning applications. Although federated learning (FL) ensures data privacy protection, server-side security concerns persist. Traditional methods have employed a blockchain system in FL frameworks to maintain a tamper-proof global model database. In this context, we propose a novel personalized federated learning (pFL) with blockchain-assisted semi-centralized framework, pFedBASC. This approach, tailored for the Internet of Things (IoT) scenarios, constructs a semi-centralized IoT structure and utilizes trusted network connections to support FL. We concentrate on designing the aggregation process and FL algorithm, as well as the block structure. To address data heterogeneity and communication costs, we propose a pFL method called FedHype. In this method, each client is assigned a compact hypernetwork (HN) alongside a normal target network (TN) whose parameters are generated by the HN. Clients pull together other clients’ HNs for local aggregation to personalize their TNs, reducing communication costs. Furthermore, FedHype can be integrated with other existing algorithms, enhancing its functionality. Experimental results reveal that pFedBASC effectively tackles data heterogeneity issues while maintaining positive accuracy, communication efficiency, and robustness.

Abstract Background Baculoviruses act as effective biological control agents against the invasive pest Hyphantria cunea Drury. In this study, two Chinese Hyphantria cunea nucleopolyhedrovirus (HycuNPV) isolates, HycuNPV-BJ and HycuNPV-HB, were deep sequenced and compared with the Japanese isolate, HycuNPV-N9, to determine whole-genome level diversity and evolutionary history. Results The divergence of the phylogenetic tree and the K2P distances based on 38 core-gene concatenated alignment revealed that two Chinese HycuNPV isolates were a novel species of Alphabaculovirus that infected Hyphantria cunea in China. The gene contents indicated significant differences in the HycuNPV genomes between the Chinese and Japanese isolates. The differences included gene deletions, acquisitions and structural transversions, but the main difference was the high number of single nucleotide polymorphisms (SNPs). In total, 10,393 SNPs, corresponding to approximately 8% of the entire HycuNPV-N9 genome sequence, were detected in the aligned reads. By analyzing non-synonymous variants, we found that hotspot mutation-containing genes had mainly unknown functions and most were early expressing genes. We found that the hycu78 gene which had early and late promoter was under positive selection. Biological activity assays revealed that the infectivity of HycuNPV-HB was greater than that of HycuNPV-BJ, and the killing speed of HycuNPV-HB was faster than that of HycuNPV-BJ. A comparison of molecular genetic characteristics indicated that the virulence differences between the two isolates were affected by SNP and structural variants, especially the homologous repeat regions. Conclusions The genomes of the two Chinese HycuNPV isolates were characterized, they belonged to a novel species of Alphabaculovirus that infected Hyphantria cunea in China. We inferred that the loss or gain of genetic material in the HycuNPV-HB and HycuNPV-BJ genomes resulted in new important adaptive capabilities to the H. cunea host. These results extend the current understanding of the genetic diversity of HycuNPV and will be useful for improving the applicability of this virus as a biological control agent.

Polysaccharides including water-soluble fraction (W), 1,2-Cyclohexanediaminetetraacetic acid (CDTA)-soluble fraction (CA), sodium carbonate (Na2CO3)-soluble fraction (SC), 1 M potassium hydroxide (KOH)-soluble fractions (PH1), and 4 M KOH-soluble fraction (PH4) were successively extracted from Dendrocalamus brandisii bamboo shoot shells using water, CDTA, Na2CO3, and KOH solution. The analytical methods were employed to initially identify the structural characteristics of the five polysaccharide fractions, and their antioxidant capacities in vitro were determined. According to the data, the average molecular weight of the five polysaccharide fractions was between 4 816 and 993 935 Da. In all four types (CA, SC, PH1, and PH4), xylose was the most abundant monosaccharide, especially in PH1 and PH4. Both PH1 and PH4 were found to contain 1,4-β-d-Xylp as their main chain, as determined by nuclear magnetic resonance (NMR) spectroscopy. Additional research into CA and SC's antioxidant potential is required since they both showed potent in vitro antioxidant activities.

Hemicellulose is the second most abundant carbohydrate in lignocellulosic biomass and has extensive applications. In conventional biomass refinery, hemicellulose is easily converted to unwanted by-products in pretreatment and therefore can't be fully utilized. The present study aims to summarize the most recent development of lignocellulosic polysaccharide degradation and fully convert it to value-added bioproducts through microbial and enzymatic catalysis. Firstly, bioprocess and microbial metabolic engineering for enhanced utilization of lignocellulosic carbohydrates were discussed. The bioprocess for degradation and conversion of natural lignocellulose to monosaccharides and organic acids using anaerobic thermophilic bacteria and thermostable glycoside hydrolases were summarized. Xylose transmembrane transporting systems in natural microorganisms and the latest strategies for promoting the transporting capacity by metabolic engineering were summarized. The carbon catabolite repression effect restricting xylose utilization in microorganisms, and metabolic engineering strategies developed for co-utilization of glucose and xylose were discussed. Secondly, the metabolic pathways of xylose catabolism in microorganisms were comparatively analyzed. Microbial metabolic engineering for converting xylose to value-added bioproducts based on redox pathways, non-redox pathways, pentose phosphate pathway, and improving inhibitors resistance were summarized. Thirdly, strategies for degrading lignocellulosic polysaccharides and fully converting hemicellulose to value-added bioproducts through microbial metabolic engineering were proposed.

China has had explosive growth in ischemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to explore the possible combination effect between gut microbiota and traditional potentially modifiable risk factors for IS among two ethnic minorities (Tujia and Miao) and the Han population. Herein, we first used the 16 S rRNA sequencing to compare the gut microbial compositions of 82 patients with first-ever IS vs. 82 normal controls (NCs) among Han, Tujia, and Miao people between 1 May 2018 and 30 April 2019, from Xiangxi Tujia and Miao Autonomous Prefecture in China. An additive model was used to study the interaction between traditional risk factors and gut microbiota with R software. Linear discriminant analysis (LDA) and LDA effect size (LEfSe) results showed that the identified key gut microbiota's taxonomic composition varied in different ethnicity between the IS patients and NCs. Furthermore, families Lactobacillaceae, Enterococcaceae, Streptococcaceae, and Enterobacteriaceae were found to be positively correlated with high-risk factors and negatively correlated with preventive factors in the IS patients, but families Ruminococcaceae and Lachnospiraceae were just the opposite in the NCs. There were additive interactions between traditional risk factors (systolic blood pressure, diastolic blood pressure, and high-sensitive C-reactive protein) and family Enterococcaceae for first-ever IS with the attributable proportion due to the interaction was 0.74, 0.71, and 0.85, respectively; and the synergy index was 4.45, 3.78, and 7.01, respectively. This preliminary but promising study showed that the gut microbiota disturbances may potentially interact to IS with different ethnic host's traditional risk factors.

Camellia fascicularis is a unique plant rich in bioactive components. However, the isolation of the active substances in C. fascicularis leaves via sequential extraction with solvents of different polarity and the determination of their antioxidant and antitumor activities have not been reported. In this study, the total methanol extract of C. fascicularis leaves was sequentially extracted with different polar solvents, and the corresponding petroleum ether extract (PEE), ethyl acetate extract (EAE), and water extract (WE) were analyzed for their contents in active substances such as flavonoids, polyphenols, polysaccharides, and saponins. The antioxidant ability of the polar extracts was investigated by determining their reducing power and the radical scavenging rate on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radicals, and CCK-8 and Annexin-FITC/propidium iodide staining assays were conducted to investigate their inhibitory effects on HCCLM6 and HGC27 tumor cells. The results showed that PEE had a high saponin content of 197.35 ± 16.21 mg OAE/g, while EAE and WE exhibited a relatively higher polysaccharide content of 254.37 ± 1.99 and 373.27 ± 8.67 mg GE/g, respectively. The EAE demonstrated the greatest reducing power and the strongest clearing abilities on ABTS and DPPH radicals with respective EC50 values of 343.45 ± 20.12 and 14.07 ± 0.06 μg/ml. Moreover, the antitumor ability of the different polar extracts was dose-dependent, with WE showing the most potent inhibitory ability against HCCLM6 and HGC27 cells.

Brucellosis is a zoonotic disease caused by a number of bacteria in the genus Brucella. In animals, classical Brucella species naturally affiliate with mammals in which they cause epididymitis and orchitis in males and abortion storms in pregnant females. Because Brucella proliferates to a vast number of free organisms in the fetal organs and fluids, abortion plays a key mechanism in disease spread in nature. B. melitensis, B. suis, and B. abortus construct the three most severe zoonotic species and their role in human brucellosis stems from their association with domesticated farm animals in which they strive and transmit the disease. Here we review the relevant literature on genus Brucella, vaccination and diagnostic approaches. Meanwhile, the prevention and control programs based on the combination of vaccination coverage of the population with differentiating serological diagnosis of the infected from vaccinated animals (DIVA) and herd clearance by a test and cull strategy using validated serological tests were discussed.

Abstract Lignin, the most abundant renewable aromatic compound in nature, is an excellent feedstock for value-added bioproducts manufacturing; while the intrinsic heterogeneity and recalcitrance of which hindered the efficient lignin biorefinery and utilization. Compared with chemical processing, bioprocessing with microbial and enzymatic catalysis is a clean and efficient method for lignin depolymerization and conversion. Generally, lignin bioprocessing involves lignin decomposition to lignin-based aromatics via extracellular microbial enzymes and further converted to value-added bioproducts through microbial metabolism. In the review, the most recent advances in degradation and conversion of lignin to value-added bioproducts catalyzed by microbes and enzymes were summarized. The lignin-degrading microorganisms of white-rot fungi, brown-rot fungi, soft-rot fungi, and bacteria under aerobic and anaerobic conditions were comparatively analyzed. The catalytic metabolism of the microbial lignin-degrading enzymes of laccase, lignin peroxidase, manganese peroxidase, biphenyl bond cleavage enzyme, versatile peroxidase, and β-etherize was discussed. The microbial metabolic process of H-lignin, G-lignin, S-lignin based derivatives, protocatechuic acid, and catechol was reviewed. Lignin was depolymerized to lignin-derived aromatic compounds by the secreted enzymes of fungi and bacteria, and the aromatics were converted to value-added compounds through microbial catalysis and metabolic engineering. The review also proposes new insights for future work to overcome the recalcitrance of lignin and convert it to value-added bioproducts by microbial and enzymatic catalysis.

Purpose: Male cancer survivors represent an important at-risk population for COVID-19. The COVID-19 pandemic requires a global response for this most vulnerable population. This study purpose was to explore whether fear of COVID-19 and fear of cancer recurrence are related to the likelihood of remaining at work following treatment in male cancer survivors. Survivors and methods: A cross-sectional survey was used. Data were collected in China in May to June 2020. The Fear of COVID-19 Scale, Fear of Cancer Recurrence (FCR) Inventory-Short Form and work sustainability subscale of the Readiness for Return to Work Scale were completed by male cancer survivors. Results: A total of 121 employed male cancer survivors participated in this study. Fear of COVID-19 and fear of cancer recurrence were both negatively correlated with work sustainability (β = -0.11, and β = -0.19, respectively). Significant interaction effects between fear of COVID-19 and fear of cancer recurrence were observed (β = 0.46, P < 0.01). Advanced disease stage, undergoing radiation therapy and having recently completed cancer treatment were all factors related to lower work sustainability scores (β = -0.28, β = -0.15, and β = -0.17, respectively). The overall path model yielded a good fit: χ2/df = 1.12 (P = 0.24), RMSEA = 0.07, TLI = 0.98, CFI = 0.99, IFI = 0.92, and NFI = 0.96. Conclusion: Fear of COVID-19 is a mediator between fear of cancer recurrence and work sustainability among Chinese male cancer survivors. The findings also indicated that male cancer survivors with higher FCR levels reported less confidence in their ability to remain at work. This information can assist in the development of new interventions and educational programs for cancer survivors, healthcare providers and employers, to improve employees’ ability to remain at work.

Adolescence is the critical period of the formation for individual personality traits, which would be influenced by numerous factors such as the internal and external environment. In view of physical exercise as an important factor affecting the healthy development of adolescents, whether it would play an important role in the formation of adolescents’ personality traits and how it would work deserve further investigation. Based on the Ecological Systems Theory, this study has explored the relationship between physical exercise and adolescents’ personality traits, as well as the mediating effect of peer relationship and the moderating effect of parent–child relationship using 9,284 data samples. The regression results show that physical exercise has a significant positive impact on the development of personality traits such as neuroticism, conscientiousness, and agreeableness. Peer relationships exert the mediating effect between physical exercise and adolescents’ personality traits. However, parent–child relationship only moderates the effect of physical exercise on conscientiousness and agreeableness.

Abstract Background Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated. Methods The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein–protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR). Results In total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival. Conclusions SPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.

The transcriptional regulator MucR is related to normal growth, stress responses and Brucella virulence, and affects the expression of various virulence-related genes in smooth-type Brucella strains. However, the function of MucR in the rough-type Brucella canis remains unknown. In this study, we discovered that MucR protein was involved in resistance to heat stress, iron-limitation, and various antibiotics in B. canis. In addition, the expression level of various bacterial flagellum-related genes was altered in mucR mutant strain. Deletion of this transcriptional regulator in B. canis significantly affected Brucella virulence in RAW264.7 macrophage and mice infection model. To gain insight into the genetic basis for distinctive phenotypic properties exhibited by mucR mutant strain, RNA-seq was performed and the result showed that various genes involved in translation, ribosomal structure and biogenesis, signal transduction mechanisms, energy production, and conversion were significantly differently expressed in ΔmucR strain. Overall, these studies have not only discovered the phenotype of mucR mutant strain but also preliminarily uncovered the molecular mechanism between the transcriptional regulator MucR, stress response and bacterial virulence in B. canis.

Brucellosis, caused by Brucella spp., is an important zoonotic disease leading to enormous economic losses in livestock, posing a great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2, a safe and effective vaccine, is widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly humans. In this study, we used cynomolgus monkey as an animal model to evaluate the safety of the S2 vaccine strain on primates. In addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe for cynomolgus monkeys. The transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly upregulated and 315 were remarkably downregulated. The Gene Ontology (GO) classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DEGs were involved in various biological processes (BPs), including the chemokine signaling pathway, actin cytoskeleton regulation, the defense response, immune system processing, and the type-I interferon signaling pathway. The molecular functions of the DEGs were mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding, and actin-binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex, and blood microparticle. Our findings alleviate the concerns over the safety of the S2 vaccine on primates and provide a genetic basis for the response from a mammalian host following vaccination with the S2 vaccine.

Abstract Background Acetoin (3-hydroxy-2-butanone), the precursor of biofuel 2,3-butanediol, is an important bio-based platform chemical with wide applications. Fermenting the low-cost and renewable plant biomass is undoubtedly a promising strategy for acetoin production. Isothermal simultaneous saccharification and fermentation (SSF) is regarded as an efficient method for bioconversion of lignocellulosic biomass, in which the temperature optima fitting for both lignocellulose-degrading enzymes and microbial strains. Results A thermotolerant (up to 52 °C) acetoin producer Bacillus subtilis IPE5-4 which simultaneously consumed glucose and xylose was isolated and identified. By compound mutagenesis, the mutant IPE5-4-UD-4 with higher acetoin productivity was selected. When fermenting at 50 °C in a 5-L bioreactor using glucose as the feedstock by strain IPE5-4-UD-4, the acetoin concentration reached 28.83 ± 0.91 g L−1 with the acetoin yield and productivity of 0.34 g g−1 glucose and 0.60 g L−1 h−1, respectively. Furthermore, an optimized and thermophilic SSF process operating at 50 °C was conducted for acetoin production from alkali-pretreated corncob (APC). An acetoin concentration of 12.55 ± 0.28 g L−1 was achieved by strain IPE5-4-UD-4 in shake flask SSF, with the acetoin yield and productivity of 0.25 g g−1 APC and 0.17 g L−1 h−1. Meanwhile, the utilization of cellulose and hemicellulose in the SSF approach reached 96.34 and 93.29%, respectively. When further fermented at 50 °C in a 5-L bioreactor, the concentration of acetoin reached the maximum of 22.76 ± 1.16 g L−1, with the acetoin yield and productivity reaching, respectively, 0.46 g g−1 APC and 0.38 g L−1 h−1. This was by far the highest acetoin yield in SSF from lignocellulosic biomass. Conclusions This thermophilic SSF process provided an efficient and economical route for acetoin production from lignocellulosic biomass at ideal temperature for both enzymatic hydrolysis and microbial fermentation.

Brucellosis is one of the most common zoonotic epidemics with a serious threat to public health and livestock development in many countries across the world. Vaccination is a key control strategy toward preventing brucellosis in high-prevalence regions. Recently, a rough-type Brucella melitensis mutant strain (RM57) induced from a B. melitensis strain M1981 showed protective effects in guinea pigs indicating that it is a good vaccine candidate. In this study, stress response assays were performed to reveal the mechanisms underlying virulence attenuation of RM57. In addition, a genome-wide transcriptome profile of RM57 was analyzed relative to the parent strain M1981 in order to reveal genetic factors controlling the phenotypes. Our results indicated a similar sensitivity to various stress conditions in RM57 owing to a lack of significant differences from its parent strain. Transcriptome analysis showed that a total of 1,205 genes were differentially expressed between RM57 and M1981 with gene ontology terms revealing that these genes are involved in energy production and conversion, translation, ribosomal structure, and biogenesis. Pathway enrichment analysis revealed that genes involved in oxidative phosphorylation, ribosome, nitrogen metabolism, tyrosine metabolism, and two-component system were significantly affected. As a result of these differences at the molecular level, the function of type IV secretion system in RM57 was found to be affected leading to reduced virulence of the RM57 mutant strain in both macrophage and mice infection models.

With the problem of environmental pollution and energy shortage becoming more and more serious, the fuel efficiency of automobile engines has attracted much attention, and variable valve technology is one of the important technologies to solve this problem. A novel fully variable valve actuation (FVVA) system based on a brushless direct current motor (BLDCM) is designed to achieve fully variable valve adjustment. The system uses a crank-moving guide rod mechanism to convert the rotary motion of the BLDCM into the linear motion of the valve. The fully variable valve system can realize real-time continuous adjustment of valve operating parameters through the motion control of BLDCM, including variable valve timing, variable valve opening duration, and variable lift. A BLDCM and a transmission mechanism for the FVVA system is designed in this paper. In order to better analyze the performance of the system, a dynamic model is established. Then, a three closed-loop control method is adopted to realize position control of the valve. Finally, a complete system model is established to verify the theory conclusions. The results show that the system can realize fully variable valve adjustment.

Brucella spp. are intracellular pathogens that infect a wide variety of mammals including humans, posing threats to the livestock industry and human health in developing countries. A number of genes associated with the intracellular trafficking and multiplication have so far been identified in Brucella spp. However, the sophisticated post-transcriptional regulation and coordination of gene expression that enable Brucella spp. to adapt to changes in environment and to evade host cell defenses are not fully understood. Bacteria small RNAs (sRNAs) play a significant role in post-transcriptional regulation, which has already been confirmed in a number of bacteria but the role of sRNAs in Brucella remains elusive. In this study, we identified several different sRNAs in Brucella spp., and found that over-expression of a sRNA, tentatively termed BASI74, led to alternation in virulence of Brucella in macrophage infection model. The expression level of BASI74 increased while Brucella abortus 2308 was grown in acidic media. In addition, BASI74 affected the growth ratio of the Brucella cells in minimal media and iron limiting medium. Using a two-plasmid reporter system, we identified four genes as the target of BASI74. One target gene, BABI1154, was predicted to encode a cytosine-N4-specific DNA methyltransferase, which protects cellular DNA from the restriction endonuclease in Brucella. These results show that BASI74 plays an important role in Brucella survival in macrophage infection model, speculatively by its connection with stress response or impact on restriction-modification system. Our study promotes the understanding of Brucella sRNAs, as well as the mechanism by which sRNAs use to influence Brucella physiology and pathogenesis.

MicroRNAs (miRNAs) are a kind of small non-coding RNA molecules that could regulate multiple biological pathways at posttranscriptional level. Over 2,000 miRNAs have so far been discovered in humans, and many of them are found to be linked to various kinds of diseases. Thus, miRNAs are being considered as clinical diagnostic and therapeutic targets. With the discovery of high stability of circulating miRNAs in various kinds of mammalian body fluids, the potential of circulating miRNAs as diagnostic/prognostic biomarkers of infectious diseases aroused great interest among researchers. As far as human diseases are concerned, some biomarkers based on circulating miRNAs have been progressed to clinical application. In veterinary fields, however, this concept is only beginning to come into view. In this review, we summarize an update of preclinical studies on using circulating miRNAs as diagnostic biomarkers to combat infectious diseases that affect domestic animals.

Caldicellulosiruptor lactoaceticus 6A, an anaerobic and extremely thermophilic bacterium, uses natural xylan as carbon source. The encoded genes of C. lactoaceticus 6A for glycoside hydrolase (GH) provide a platform for xylan degradation. The GH family 10 xylanase (Xyn10A) and GH67 α-glucuronidase (Agu67A) from C. lactoaceticus 6A were heterologously expressed, purified and characterized. Both Xyn10A and Agu67A are predicted as intracellular enzymes as no signal peptides identified. Xyn10A and Agu67A had molecular weight of 47.0 kDa and 80.0 kDa respectively as determined by SDS-PAGE, while both appeared as homodimer when analyzed by gel filtration. Xyn10A displayed the highest activity at 80 °C and pH 6.5, as 75 °C and pH 6.5 for Agu67A. Xyn10A had good stability at 75 °C, 80 °C, and pH 4.5-8.5, respectively, and was sensitive to various metal ions and reagents. Xyn10A possessed hydrolytic activity towards xylo-oligosaccharides (XOs) and beechwood xylan. At optimum conditions, the specific activity of Xyn10A was 44.6 IU/mg with beechwood xylan as substrate, and liberated branched XOs, xylobiose, and xylose. Agu67A was active on branched XOs with methyl-glucuronic acids (MeGlcA) sub-chains, and primarily generated XOs equivalents and MeGlcA. The specific activity of Agu67A was 1.3 IU/mg with aldobiouronic acid as substrate. The synergistic action of Xyn10A and Agu67A was observed with MeGlcA branched XOs and xylan as substrates, both backbone and branched chain of substrates were degraded, and liberated xylose, xylobiose, and MeGlcA. The synergism of Xyn10A and Agu67A provided not only a thermophilic method for natural xylan degradation, but also insight into the mechanisms for xylan utilization of C. lactoaceticus.

The xylanolytic extremely thermophilic bacterium Caldicellulosiruptor owensensis provides a promising platform for xylan utilization. In the present study, two novel xylanolytic enzymes, GH10 endo-β-1,4-xylanase (Coxyn A) and GH39 β-1,4-xylosidase (Coxyl A) encoded in one gene cluster of C.owensensis were heterogeneously expressed and biochemically characterized. The optimum temperature of the two xylanlytic enzymes was 75°C, and the respective optimum pH for Coxyn A and Coxyl A was 7.0 and 5.0. The difference of Coxyn A and Coxyl A in solution was existing as monomer and homodimer respectively, it was also observed in predicted secondary structure. Under optimum condition, the catalytic efficiency (kcat/Km) of Coxyn A was 366 mg ml(-1) s(-1) on beechwood xylan, and the catalytic efficiency (kcat/Km) of Coxyl A was 2253 mM(-1) s(-1) on pNP-β-D-xylopyranoside. Coxyn A degraded xylan to oligosaccharides, which were converted to monomer by Coxyl A. The two intracellular enzymes might be responsible for xylooligosaccharides utilization in C.owensensis, also provide a potential way for xylan degradation in vitro.

Fatty acids and their derivatives are indispensable biomolecules in all organisms, and can be used as intermediates in the synthesis of pharmaceuticals, biofuels and pesticides, and thus their demand has increased dramatically in recent years. In addition to serving as structural components of cell membranes and metabolic energy, fatty acids and their derivatives can also be used as signal transduction and regulatory bioactive molecules to regulate cell functions. Biosynthesis of fatty acids and their derivatives through microbial catalysis provides green and alternative options to meet the goal. However, the low biosynthetic titer of fatty acids and their derivatives limits their industrial production and application. In this review, we first summarize the metabolic pathways and related enzymes of fatty acids and their derivatives biosynthesis. Then, the strategies and research progress of biosynthesis of fatty acids and derivatives through metabolic and enzyme engineering were reviewed. The biosynthesis of saturated fatty acids (medium chain fatty acids and long chain fatty acids), bioactive fatty acids (PUFAs, oxylipins, ether lipids), and their derivatives with microbial and enzymatic catalysis were respectively summarized. Finally, synthetic biology strategies to improve fatty acids and their derivatives production through enzyme rational design, carbon metabolism flux, cofactors balance, and metabolic pathways design were discussed. The review provides references and prospects for fatty acids and their derivatives biosynthesis and industrial production. [ABSTRACT FROM AUTHOR]

Objective: Conventional cervical lymph node dissection often leaves large surgical scars, which seriously compromises the postoperative aesthetic effect and can affect the quality of life of patients. In this study, the safety and feasibility of robotic-assisted endoscopic thyroidectomy with central neck dissection (CND) and lateral neck dissection (LND) via a combined transoral and breast approach are discussed in detail. Materials and methods: A retrospective analysis wasmade of the data of 26 patients with stage cN1b papillary thyroid carcinoma who were admitted to the Thyroid Surgery Department of the Hunan Cancer Hospital fromMarch 2021 to September 2022 and who underwent roboticassisted endoscopic thyroidectomy with LND via a combined transoral and breast approach. The demographic data, surgical indicators, postoperative data, and the postoperative complication rate of the patients were analyzed, and the learning curve was analyzed by cumulative summation. Results: All the patients underwent endoscopic surgery without any conversion to open surgery. The mean operation time was 313.7±50.3min and the mean number of total positive/retrieved lymph nodes was 11.2±8.1/36.8±13.7. Two patients developed temporary laryngeal recurrent nerve palsy and three patients developed temporary hypoparathyroidism, all of whom recovered within 3 months postoperatively. No tumor recurrence occurred during follow-ups that ranged from 6 to 24 months. The mean postoperative quality of life (QOL) score was 189.1±118.2, test results ranging from 0 to 1300 with a lower score indicating a higher QOL, and the aesthetic satisfaction score was 4.2±0.7, test scores ranging from 0 to 5 with higher scores indicate higher satisfaction. The turning point of the learning curve was in the 11th case. Conclusions: The robotic-assisted endoscopic thyroidectomy with CND and LND via a combined transoral and breast approach is safe and feasible, and the improved cosmetic effect is remarkable, which is conducive to improving the postoperative QOL of patients. It provides a new surgical option for patients. [ABSTRACT FROM AUTHOR]

Methane is abundant in nature, and excessive emissions will cause the greenhouse effect. Methane is also an ideal carbon and energy feedstock for biosynthesis. In the review, the microorganisms, metabolism, and enzymes for methane utilization, and the advances of conversion to value-added bioproducts were summarized. First, the physiological characteristics, classification, and methane oxidation process of methanotrophs were introduced. The metabolic pathways for methane utilization and key intermediate metabolites of native and synthetic methanotrophs were summarized. Second, the enzymatic properties, crystal structures, and catalytic mechanisms of methane-oxidizing and metabolizing enzymes in methanotrophs were described. Third, challenges and prospects in metabolic pathways and enzymatic catalysis for methane utilization and conversion to value-added bioproducts were discussed. Finally, metabolic engineering of microorganisms for methane biooxidation and bioproducts synthesis based on different pathways were summarized. Understanding the metabolism and challenges of microbial methane utilization will provide insights into possible strategies for efficient methane-based synthesis. [ABSTRACT FROM AUTHOR]

Cupriavidus necator H16 is an ideal strain for polyhydroxybutyrate (PHB) production from CO2. Low-oxygen stress can induce PHB synthesis in C. necator H16 while reducing bacterial growth under chemoautotrophic culture. The optimum growth and PHB synthesis of C. necator H16 cannot be achieved simultaneously, which restricts PHB production. The present study was initiated to address the issue through comparative transcriptome and gene function analysis. First, the comparative transcriptome of C. necator H16 chemoautotrophically cultured under low-oxygen stress and nonstress conditions was studied. Three types of genes were discovered to have differential levels of transcription: those involving PHB enzymatic synthesis, PHB granulation, and regulators. Under low-oxygen stress conditions, acetoacetyl-coenzyme A (CoA) reductase gene phaB2, PHB synthase gene phaC2, phasins genes phaP1 and phaP2, and regulator genes uspA and rpoN were upregulated 3.0-, 2.5-, 1.8-, 2.7-, 3.5-, and 1.6-fold, respectively. Second, the functions of upregulated genes and their applications in PHB synthesis were further studied. It was found that the overexpression of phaP1, phaP2, uspA, and rpoN can induce PHB synthesis under nonstress conditions, while phaB2 and phaC2 have no significant effect. Under the optimum conditions, the PHB percentage content in C. necator H16 was increased by 37.2%, 28.4%, 15.8%, and 41.0%, respectively, with overexpression of phaP1, phaP2, uspA, and rpoN, and the corresponding PHB production increased by 49.8%, 42.9%, 47.0%, and 77.5%, respectively, under nonstress chemoautotrophic conditions. Similar promotion by phaP1, phaP2, uspA, and rpoN was observed in heterotrophically cultured C. necator H16. The PHB percentage content and PHB production were increased by 54.4% and 103.1%, respectively, with the overexpression of rpoN under nonstress heterotrophic conditions. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have been reported to be dysregulated and play a crucial role in the progression of cancer. LncRNA DANCR has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including osteosarcoma, gastric cancer, breast cancer, hepatocellular carcinoma, and colorectal cancer. However, the expression profiles and biological relevance of DANCR in papillary thyroid cancer (PTC) have not yet been reported. In the present study, the expression level of DANCR in PTC tissues and adjacent normal tissues was detected by reverse transcription-quantitative PCR in PTC patients, and then we analyzed the association with clinical pathological characteristics of patients and DANCR expressions. These results demonstrated that the expression of DANCR was notably decreased in tumor tissues in comparison with adjacent normal tissues (P<0.001). Furthermore, the present study found that DANCR expression level was correlated to T grade (P<0.01) and TNM stage (P=0.017). The present study demonstrated that DANCR was associated with PTC aggressive clinical features and may serve as a diagnostic biomarker for detecting PTC patients. [ABSTRACT FROM AUTHOR]

MiR-140-5p is low expression and acts as a tumor suppressor in various types of human cancers. However, the potential role of miR-140-5p in retinoblastoma (RB) remains unknown. In the present study, we performed the miRNA microarray analysis to investigate whether miRNAs expression are associated with RB tumorigenesis in RB tissues. We found that a large set of miRNAs were ectopic expressions and miR-140-5p is most significantly down-regulated in human RB tissues compared with normal retinas. In addition, low miR-140-5p expression is associated with clinicopathological features (differentiation, invasion, T classification, N classification, cTNM stage, and largest tumor base) and poor survival in RB patients. Furthermore, our results showed that overexpression of miR-140-5p suppresses proliferation and induces apoptosis and cell cycle arrest in RB cell. Meanwhile, we confirmed that c-Met is the functional target of miR-140-5p in RB cell, and miR-140-5p expression is negatively correlated with c-Met in RB tissues. We also found that inhibition of c-Met also suppresses proliferation and induces apoptosis and cell cycle arrest in RB cell. Interestingly, c-Met can rescue the suppressive effects ofmiR-140-5p on RB cell growth and cell cycle arrest. More importantly, our findings indicated that miR-140-5p may inhibit cell growth via blocking c-Met/AKT/mTOR signaling pathway. Collectively, these results suggested that miR-140-5p might be a potential biomarker and target in the diagnosis and treatment of RB. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the occurrence and clinical features of cases of multiple primary cancers including colorectal cancer (MPCC). The medical records of patients with colorectal cancer (CRC) who underwent surgery at the Third Xiangya Hospital of Central South University (Changsha, China) between August 2007 and August 2014 were retrospectively analyzed. Patients with MPCCs were identified and mutation analyses were performed on colon specimens. The results revealed that among 1,311 patients with CRC, 59 had MPCC (including 35 cases of =1 CRC with =1 other cancer type, and 24 cases with multiple CRCs and no other primary cancers). Foci occurred on the right side of the colon (n=32), in the rectum (n=28), and on the left side of the colon (n=24). MPCCs were synchronous in 24 patients, metachronous in 32 patients, and both in 3 patients. Age of onset and presence of polyps were identified as significantly different between MPCC and CRC overall (P<0.05); however, sex or adenoma incidence were not observed to differ significantly between groups. Mutation incidence rates in 26 specimens were 11.54% for KRAS proto-oncogene GTPase (KRAS) G13D, 3.85% for KRAS Q61R and 3.85% B-Raf proto-oncogene serine/threonine kinase V600E. Mutations of exon 21 of the epithelial growth factor receptor gene, including L858R and L861Q, and of KRAS G12V were not detected. In conclusion, the likelihood of occurrence of MPCC is closely associated with the age of onset and the presence of polyp(s). Routine examination of multiple systems is necessary for patients with CRC to avoid missed diagnosis and misdiagnosis. Further study is required to demonstrate the molecular mechanism of CRC in cases of multiple primary cancers. [ABSTRACT FROM AUTHOR]

Pollutant emission characteristics and the synergistic interaction during low-temperature oxidation of blended coal were investigated. Two kinds of bituminous coals, high volatile bituminous coal (HC) and low volatile bituminous coal (LC), and their blends were heated from room temperature to 300 °C by 2 °C/min under air atmosphere, controlled and measured with the TGA-FTIR. The results showed that CO2 emission was affected by both moisture content and pore structure of coal. The blended ratio of 60HC40LC inhibited CO2 emission for the coupling effect of moisture content and pore structure. The minerals like sodium and potassium contributed to SO2 generation, while calcium and magnesium inhibited SO2 generation, thus the blended ratio of 40HC60LC inhibited SO2 emission with the synergistic interaction. What's more, the blended coal could reduce HCN and HCl emission in different blended ratio. Thereby, blended coal technology was an effective way to reduce pollutant emission during lowtemperature oxidation. [ABSTRACT FROM AUTHOR]