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Acinetobacter baumannii, especially multidrug resistant Acinetobacter baumannii, is a notable source of pressure in the areas of public health and antibiotic development. To overcome this problem, attention has been focused on membrane proteins. Different digestion methods and extraction detergents were examined for membrane proteome sample preparation, and label-free quantitative and targeted proteome analyses of the polymyxin B-induced Acinetobacter baumannii ATCC 19606 membrane proteome were performed based on nano LC-MS/MS. Ultracentrifugation of proteins at a speed of 150,000×g, digestion by trypsin, filter-aided sample preparation, and detergents such as lauryldimethylamine-N-oxide were proved as a fast and effective way for identification of membrane proteome by nano LC-MS/MS. Upon treatment with polymyxin B, expression levels of 15 proteins related to membrane structure, transporters, cell surface, and periplasmic space were found to be significantly changed. Furthermore, targeted proteome was also used to confirm these changes. A relatively rapid membrane proteome preparation method was developed, and a more comprehensive view of changes in the Acinetobacter baumannii membrane proteome under polymyxin B pressure was obtained.

An accurate and reliable susceptibility testing method for polymyxins is urgently needed not only for the clinical laboratory but also for new polymyxin-like lipopeptide development. Reference broth microdilution (rBMD), which was the recommended method by CLSI-EUCAST in clinics, has been proven not to be ideal, while the agar dilution (AD) method that was widely used in new antibiotics discovery has been neglected. In the present study, the AD method was compared with rBMD and broth macrodilution (BMAD) in susceptibility testing of polymyxin B and colistin against >200 Gram-negative isolates. AD showed strong agreement with BMAD for colistin (except for Klebsiella aerogenes and Pseudomonas aeruginosa); however, its performance was poor for polymyxin B or compared to rBMD. MICs of AD method were not affected when different types of Petri dishes were used, while glass-bottom microtiter plates could lower the MIC of polymyxins 2–8 times compared to tissue-culture-treated polystyrene plates when using rBMD, which demonstrated that tissue-culture-treated plates were not suitable. It was then validated with non-tissue-culture-treated plates. The culture volume was another influencing factor of accuracy for rBMD, and 200 μL seemed to be the most suitable volume for MIC detection of polymyxins. Additionally, no lack of growth phenomenon (skipped well) was observed for AD when it frequently occurred for both BMAD and rBMD. As for strains carrying mcr-1 gene, 100% of AD results were in essential agreement (EA) and categorical agreement (CA) with both rBMD and BMAD. Overall, rBMD is convenient and widely accepted for susceptibility testing of polymyxins. Although it may be too early to say that AD is superior compared to rBMD and BMAD, it did show some advantages in repeatability and anti-interference ability.

Lactobacilli have been widely concerned for decades. Bacteria of the genus Lactobacillus have been commonly employed in fermented food to improve the appearance, smell, and taste of food or prolong its shelf-life. They comprise 261 species (by March 2020) that are highly diverse at the phenotypic, ecological, and genotypic levels. Some Lactobacilli strains have been documented to be essential probiotics, which are defined as a group of living microorganisms that are beneficial to the health of the host when ingested in sufficiency. However, the characterization, high-density fermentation, and the production of a directed vat set (DVS) starter of Lactobacilli strains used in the food industry have not been systematically reported. This paper mainly focuses on reviewing Lactobacilli as functional starter cultures in the food industry, including different molecular techniques for identification at the species and strain levels, methods for evaluating Lactobacilli properties, enhancing their performance and improving the cell density of Lactobacilli, and the production techniques of DVS starter of Lactobacilli strains. Moreover, this review further discussed the existing problems and future development prospects of Lactobacilli in the food industry. The viability and stability of Lactobacilli in the food industry and gastrointestinal environment are critical challenges at the industrial scale. The new production equipment and technology of DVS starter of Lactobacilli strains will have the potential for large-scale application, for example, developing low-temperature spray drying, freezing granulation drying, and spray freeze-drying.

Severe hyperdivergent skeletal Class II malocclusion may be ideally treated with orthognathic surgery in adult patients. Here, we report a camouflage treatment of a 23-year-old female patient. She was diagnosed with a skeletal Class II malocclusion with extreme high mandibular plane angle, retrusive mandible, steep posterior occlusal plane, anterior open bite, and severe overjet. The treatment plan included extraction of all second premolars and intrusion of the maxillary anterior teeth and mandibular posterior teeth using miniscrews. These contributed to an effective counterclockwise rotation of the mandible, decreased lower face height, and improvement in anterior overbite. This case report shows a vertical control strategy on severe hyperdivergent skeletal Class II malocclusions, which achieves well-controlled sagittal and vertical dimensions and a favorable facial appearance. The treatment and retention results were well balanced and aesthetically pleasing.

Cholangiocarcinoma (CCA) is a lethal malignancy in the hepatobiliary system, with dysregulated protein expression and phosphorylation signaling. However, the protein and phosphorylation signatures of CCAs are little-known. Here, we performed the proteomic and phosphoproteomic profiling of tumors and normal adjacent tissues (NATs) from patients with CCA and predicted eleven PKs high-potentially related to CCA with a comprehensive inference of the functional protein kinases (PKs) (CifPK) pipeline. Besides the two known CCA-associated PKs, we screened the remaining candidates and uncovered five PKs as novel regulators in CCA. Specifically, the protein kinase D (PKD) family members, including PRKD1, PRKD2, and PRKD3, were identified as critical regulators in CCA. Moreover, the pan-inhibitor of the PKD family, 1-naphthyl PP1 (1-NA-PP1), was validated as a potent agent for inhibiting the proliferation, migration, and invasion ability of CCA cells. This study reveals new PKs associated with CCA and suggests PRKD kinases as novel treatment targets for CCA.

Adequate alveolar bone volume is a prerequisite condition for successful orthodontic tooth movement and posttreatment stability. Mandibular anterior teeth are more likely to exhibit dehiscence and fenestration in adult patients, which make orthodontic treatment in adults challenging, especially when the amount of retraction of the anterior teeth is large. Herein, we report the treatment of augmented corticotomy only on the lingual side in the mandibular anterior region to increase the volume of soft and hard tissue assisting orthodontics in a Class I bialveolar protrusive malocclusion and propose management strategies of mandibular incisor retractions. A 22-year-old female with a chief complaint of protrusive mouth presented to the Department of Orthodontics for orthodontic treatment, diagnosed with Class I bialveolar protrusive. The orthodontic treatment plan involved the extraction of four premolars and extensive retraction of the anterior teeth using microimplant anchorage. In consideration of the fenestration and dehiscence in the mandibular anterior alveolar bone and the pattern of tooth movement, augmented corticotomy was performed on the lingual side combined with bone grafting. Clinical and radiographic evaluation after treatment revealed significant improvements in the facial profile and in periodontal phenotype. Augmented corticotomy assisting orthodontic treatment could be a promising treatment strategy for adult patients with alveolar protrusion to maintain periodontal health.

China’s construction industry is an important driving force for the development of society. Nevertheless, with the recent new normal of economic development, traditional construction approaches cannot meet the requirements of socialist modernization and sustainable construction. As such, the development of the construction industry needs to match the recent developmental concept of green environmental protection. Therefore, China’s construction industry needs to explore innovative development paths of transformation and upgrading. Recently, the Chinese government has been vigorously promoting building information modeling (BIM) applications. However, in the real-world construction process, BIM applications have not achieved their expected impacts. To satisfy the practical demands, this research uses the social network analysis method to analyze the key hindering factors in order to clarify the significance and influencing mechanism of each factor. The current study identified 12 key hindering factors that impede the development of BIM applications in China’s construction industry. The results show that a lack of policy guidance and the restriction of relevant laws are the most critical hindering factors. This research contributes to the research of the hindering factors of BIM applications in China and can assist decision makers in formulating appropriate strategies to promote the application and development of information BIM technology in China’s construction industry.

Iron is a vital element in nearly every living organism. During pregnancy, optimal iron concentration is essential for both maternal health and fetal development. As the barrier between the mother and fetus, placenta plays a pivotal role in mediating and regulating iron transport. Imbalances in iron metabolism correlate with severe adverse pregnancy outcomes. Like most other nutrients, iron exhibits a U-shaped risk curve. Apart from iron deficiency, iron overload is also dangerous since labile iron can generate reactive oxygen species, which leads to oxidative stress and activates ferroptosis. In this review, we summarized the molecular mechanism and regulation signals of placental iron trafficking under physiological conditions. In addition, we revealed the role of iron metabolism and ferroptosis in the view of preeclampsia and gestational diabetes mellitus, which may bring new insight to the pathogenesis and treatment of pregnancy-related diseases.

Summary: Tumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.

The brain is considered to be an extremely sensitive tissue to hypoxia, and the brain of fish plays an important role in regulating growth and adapting to environmental changes. As an important aquatic organism in northern China, the economic yield of Takifugu rubripes is deeply influenced by the oxygen content of seawater. In this regard, we performed RNA-seq analysis of T. rubripes brains under hypoxia and normoxia to reveal the expression patterns of genes involved in the hypoxic response and their enrichment of metabolic pathways. Studies have shown that carbohydrate, lipid and amino acid metabolism are significant pathways for the enrichment of differentially expressed genes (DEGs) and that DEGs are significantly upregulated in those pathways. In addition, some biological processes such as the immune system and signal transduction, where enrichment is not significant but important, are also discussed. Interestingly, the DEGs associated with those pathways were significantly downregulated or inhibited. The present study reveals the mechanism of hypoxia tolerance in T. rubripes at the transcriptional level and provides a useful resource for studying the energy metabolism mechanism of hypoxia response in this species.

Cobalt–chromium (Co-Cr) alloys have been widely used as dental-restoration materials for many years. This study sought to investigate whether selective laser melting (SLM) is a more appropriate process than traditional casting (CAST) for fabricating dental Co-Cr alloys. Metallurgical microscopy, X-ray photoelectron spectroscopy (XPS), Vickers hardness and nanoindentation tests, and friction and wear tests were used to evaluate the microstructure, surface compositions, mechanical properties, and wear resistance, respectively. Additionally, the biocompatibilities and cell adhesion of the alloys were evaluated with L-929 fibroblasts via CCK-8 assay, Live/Dead staining, flow cytometric analysis, scanning electron microscopy (SEM) observation and real-time PCR (RT-PCR) assay. The XPS results showed that the two alloys were all mainly comprised of Co, Cr, and O. The hardness in the CAST group equaled 7.15 ± 0.48 GPa, while in the SLM group, it equaled 9.06 ± 0.49 GPa. The friction coefficient of SLM alloys remained at approximately 0.46, but the CAST specimens fluctuated significantly. SLM alloys exhibited shallower wear scars and less wear debris compared with CAST alloys, simultaneously. Additionally, there were higher survival and expression of cell-adhesion-related genes on SLM alloys of L-929 cells, which meant that the deleterious effect on L-929 cells was significantly reduced compared with that for the CAST alloys. Overall, the wear resistances and biocompatibilities of the Co-Cr dental alloys were dramatically affected by the fabrication technique. The SLM technique is advantageous over the CAST technique for fabricating Co-Cr dental alloys.

Tumor budding is considered a sign of cancer cell activity and the first step of tumor metastasis. This study aimed to establish an automatic diagnostic platform for rectal cancer budding pathology by training a Faster region-based convolutional neural network (F-R-CNN) on the pathological images of rectal cancer budding. Postoperative pathological section images of 236 patients with rectal cancer from the Affiliated Hospital of Qingdao University, China, taken from January 2015 to January 2017 were used in the analysis. The tumor site was labeled in Label image software. The images of the learning set were trained using Faster R-CNN to establish an automatic diagnostic platform for tumor budding pathology analysis. The images of the test set were used to verify the learning outcome. The diagnostic platform was evaluated through the receiver operating characteristic (ROC) curve. Through training on pathological images of tumor budding, an automatic diagnostic platform for rectal cancer budding pathology was preliminarily established. The precision–recall curves were generated for the precision and recall of the nodule category in the training set. The area under the curve = 0.7414, which indicated that the training of Faster R-CNN was effective. The validation in the validation set yielded an area under the ROC curve of 0.88, indicating that the established artificial intelligence platform performed well at the pathological diagnosis of tumor budding. The established Faster R-CNN deep neural network platform for the pathological diagnosis of rectal cancer tumor budding can help pathologists make more efficient and accurate pathological diagnoses.

Katz and colleagues examine glutamate spillover effects on C. elegans behaviour. They show that impaired synaptic glutamate clearance in glial glutamate transporter mutants, causes presynaptic mgl-2/mGluR5 activation, generating postsynaptic neural activity oscillations driving repetitive behaviour.

Abstract The adoptive transfer of human T cells or genetically-engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. The objective of this study was to develop a novel T cell biomanufacturing platform using stirred-tank bioreactor for large-scale and high-quality cellular production. First, various factors, such as bioreactor parameters, media, supplements, stimulation, seed age, and donors, were investigated. A serum-free fed-batch bioproduction process was developed to achieve 1000-fold expansion within 8 days after first stimulation and another 500-fold expansion with second stimulation. Second, this biomanufacturing process was successfully scaled up in bioreactor with dilution factor of 10, and the robustness and reproducibility of the process was confirmed by the inclusion of different donors’ T cells of various qualities. Finally, T cell quality was monitored using 12 surface markers and 3 intracellular cytokines as the critical quality assessment criteria in early, middle and late stages of cell production. In this study, a new biomanufacturing platform was created to produce reliable, reproducible, high-quality, and large-quantity (i.e. > 5 billion) human T cells in stirred-tank bioreactor. This platform is compatible with the production systems of monoclonal antibodies, vaccines, and other therapeutic cells, which provides not only the proof-of-concept but also the ready-to-use new approach of T cell expansion for clinical immune therapy.

Using Medicare claims data on prescriptions of oseltamivir dispensed to people 65 years old and older, we present a descriptive analysis of patterns of influenza activity in the United States for 579 core-based statistical areas (CBSAs) from the 2010–2011 through the 2015–2016 influenza seasons. During this time, 1,010,819 beneficiaries received a prescription of oseltamivir, ranging from 45,888 in 2011–2012 to 380,745 in 2014–2015. For each season, the peak weekly number of prescriptions correlated with the total number of prescriptions (Pearson’s r ≥ 0.88). The variance in peak timing decreased with increasing severity (p

Abstract. Background:. An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. Methods:. Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. Results:. Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. Conclusion:. Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. Trial Registration:. www.chictr.org.cn (No. ChiCTR-DDD-17013842)

Estimation of the noise power spectral density (PSD) plays a critical role in most existing single-channel speech enhancement algorithms. In this paper, we present a novel noise PSD tracking algorithm, which employs a log-spectral power minimum mean square error (MMSE) estimator. This method updates the noise PSD estimate by performing a temporal recursive averaging of log-spectral MMSE estimate of the current noise power to reduce the risk of speech leakage into noise estimate. A smoothing parameter used in the recursive operation is adjusted by speech presence probability (SPP). In this method, a spectral nonlinear weighting function is derived to estimate the noise spectral power which depends on the a priori and the a posteriori signal-to-noise ratio (SNR). An extensive performance comparison has been carried out with several state-of-the-art noise tracking algorithms, i.e., Minimum Statistics (MS), modified minima controlled recursive averaging algorithm (MCRA-2), MMSE-based method, and SPP-based method. It is clear from experimental results that the proposed algorithm exhibits more excellent noise tracking capability under various nonstationary noise environments and SNR levels. When employed in a speech enhancement framework, improved speech enhancement performance in terms of the segmental SNR (segSNR) improvements and three objective composite metrics is observed.

The 0-1 Multidimensional Knapsack Problem (MKP) is an NP-Hard problem that has many important applications in business and industry. However, business and industrial applications typically involve large problem instances that can be time consuming to solve for a guaranteed optimal solution. There are many approximate solution approaches, heuristics and metaheuristics, for the MKP published in the literature, but these typically require the fine-tuning of several parameters. Fine-tuning parameters is not only time-consuming (especially for operations research (OR) practitioners), but also implies that solution quality can be compromised if the problem instances being solved change in nature. In this paper, we demonstrate an efficient and effective implementation of a robust population-based metaheuristic that does not require parameter fine-tuning and can easily be used by OR practitioners to solve industrial size problems. Specifically, to solve the MKP, we provide an efficient adaptation of the two-phase Teaching-Learning Based Optimization (TLBO) approach that was originally designed to solve continuous nonlinear engineering design optimization problems. Empirical results using the 270 MKP test problems available in Beasley’s OR-Library demonstrate that our implementation of TLBO for the MKP is competitive with published solution approaches without the need for time-consuming parameter fine-tuning.

Abstract Background In this study, images of 2450 benign thyroid nodules and 2557 malignant thyroid nodules were collected and labeled, and an automatic image recognition and diagnosis system was established by deep learning using the YOLOv2 neural network. The performance of the system in the diagnosis of thyroid nodules was evaluated, and the application value of artificial intelligence in clinical practice was investigated. Methods The ultrasound images of 276 patients were retrospectively selected. The diagnoses of the radiologists were determined according to the Thyroid Imaging Reporting and Data System; the images were automatically recognized and diagnosed by the established artificial intelligence system. Pathological diagnosis was the gold standard for the final diagnosis. The performances of the established system and the radiologists in diagnosing the benign and malignant thyroid nodules were compared. Results The artificial intelligence diagnosis system correctly identified the lesion area, with an area under the receiver operating characteristic (ROC) curve of 0.902, which is higher than that of the radiologists (0.859). This finding indicates a higher diagnostic accuracy (p = 0.0434). The sensitivity, positive predictive value, negative predictive value, and accuracy of the artificial intelligence diagnosis system for the diagnosis of malignant thyroid nodules were 90.5%, 95.22%, 80.99%, and 90.31%, respectively, and the performance did not significantly differ from that of the radiologists (p > 0.05). The artificial intelligence diagnosis system had a higher specificity (89.91% vs 77.98%, p = 0.026). Conclusions Compared with the performance of experienced radiologists, the artificial intelligence system has comparable sensitivity and accuracy for the diagnosis of malignant thyroid nodules and better diagnostic ability for benign thyroid nodules. As an auxiliary tool, this artificial intelligence diagnosis system can provide radiologists with sufficient assistance in the diagnosis of benign and malignant thyroid nodules.

DNA damage repair and tumor hypoxia contribute to intratumoral cellular and molecular heterogeneity and affect radiation response. The goal of this study is to investigate anti-HER2-induced radiosensitization of the tumor microenvironment to enhance fractionated radiotherapy in models of HER2+ breast cancer. This is monitored through in vitro and in vivo studies of phosphorylated γ-H2AX, [18F]-fluoromisonidazole (FMISO)-PET, and transcriptomic analysis. In vitro, HER2+ breast cancer cell lines were treated with trastuzumab prior to radiation and DNA double-strand breaks (DSB) were quantified. In vivo, HER2+ human cell line or patient-derived xenograft models were treated with trastuzumab, fractionated radiation, or a combination and monitored longitudinally with [18F]-FMISO-PET. In vitro DSB analysis revealed that trastuzumab administered prior to fractionated radiation increased DSB. In vivo, trastuzumab prior to fractionated radiation significantly reduced hypoxia, as detected through decreased [18F]-FMISO SUV, synergistically improving long-term tumor response. Significant changes in IL-2, IFN-gamma, and THBS-4 were observed in combination-treated tumors. Trastuzumab prior to fractionated radiation synergistically increases radiotherapy in vitro and in vivo in HER2+ breast cancer which is independent of anti-HER2 response alone. Modulation of the tumor microenvironment, through increased tumor oxygenation and decreased DNA damage response, can be translated to other cancers with first-line radiation therapy.

Moisture content and shrinkage strain are essential parameters during the wood drying process. The accurate detection of these parameters has very important significance for controlling the drying process and minimizing drying defects. The presented study describes an electrochemical method to determine wood moisture content and shrinkage strain during drying, and the accuracy of this method is also evaluated. According to the results, the electrical resistance of the samples increased with the decrease in wood moisture content. As the moisture content changed from 42% to 12%, the resistance increased from 1.0 × 107 Ω to 1.2 × 108 Ω. A polynomial fitting curve was fitted with a determination coefficient of 0.937 to describe the relationship between moisture content and electrical resistance. In addition, both the shrinkage strain and resistance change rate increased with the decrease in wood moisture content, especially for the moisture content range of 23% to 8%, where the shrinkage strain and resistance change rate increased by 4% and 30%, respectively. The shrinkage strain increased exponentially with the increase in the resistance change rate; thereby, an exponential regression equation was proposed with a determination coefficient of 0.985, expressing the correlation between the two. This demonstrates the feasibility of the electrochemical method for measuring wood moisture content and shrinkage strain.

Magnesium alloys have gained great attention as biodegradable materials for stent applications. Cardiovascular stents are continuously exposed to different types of mechanical loadings simultaneously during service, including tensile, compressive and fluid shear stress. In this study, the in vitro degradation of WE43 wires was investigated under combined effect of tensile loading and fluid shear stress and compared with that experienced an individual loading condition. For the individual mechanical loading treatment, the degradation of magnesium wires was more severely affected by tensile loading than fluid shear stress. Under tensile loading, magnesium wires showed faster increment of corrosion rates, loss of mechanical properties and localized corrosion morphology with the increasing tensile loadings. With the combined stress, smaller variation of the corrosion rates as well as the slower strength degeneration was shown with increasing stress levels, in comparison with the individual treatment of tensile loading. This study could help to understand the effect of complex stress condition on the corrosion of magnesium for the optimization of biodegradable magnesium stents. Keywords: Magnesium alloys, Degradation, Stent, Stress

Summary: Animal nervous systems remodel following stress. Although global stress-dependent changes are well documented, contributions of individual neuron remodeling events to animal behavior modification are challenging to study. In response to environmental insults, C. elegans become stress-resistant dauers. Dauer entry induces amphid sensory organ remodeling in which bilateral AMsh glial cells expand and fuse, allowing embedded AWC chemosensory neurons to extend sensory receptive endings. We show that amphid remodeling correlates with accelerated dauer exit upon exposure to favorable conditions and identify a G protein-coupled receptor, REMO-1, driving AMsh glia fusion, AWC neuron remodeling, and dauer exit. REMO-1 is expressed in and localizes to AMsh glia tips, is dispensable for other remodeling events, and promotes stress-induced expression of the remodeling receptor tyrosine kinase VER-1. Our results demonstrate how single-neuron structural changes affect animal behavior, identify key glial roles in stress-induced nervous system plasticity, and demonstrate that remodeling primes animals to respond to favorable conditions.

Panax notoginseng, a perennial herb of the genus Panax in the family Araliaceae, has played an important role in clinical treatment in China for thousands of years because of its extensive pharmacological effects. Here, we report a high-quality reference genome of P. notoginseng, with a genome size up to 2.66 Gb and a contig N50 of 1.12 Mb, produced with third-generation PacBio sequencing technology. This is the first chromosome-level genome assembly for the genus Panax. Through genome evolution analysis, we explored phylogenetic and whole-genome duplication events and examined their impact on saponin biosynthesis. We performed a detailed transcriptional analysis of P. notoginseng and explored gene-level mechanisms that regulate the formation of characteristic tubercles. Next, we studied the biosynthesis and regulation of saponins at temporal and spatial levels. We combined multi-omics data to identify genes that encode key enzymes in the P. notoginseng terpenoid biosynthetic pathway. Finally, we identified five glycosyltransferase genes whose products catalyzed the formation of different ginsenosides in P. notoginseng. The genetic information obtained in this study provides a resource for further exploration of the growth characteristics, cultivation, breeding, and saponin biosynthesis of P. notoginseng.

Autophagy is an important bioprocess throughout the occurrence and development of cancer. However, the role of autophagy-related lncRNAs in pancreatic cancer (PC) remains obscure. In the study, we identified the autophagy-related lncRNAs (ARlncRNAs) and divided the PC patients from The Cancer Genome Atlas into training and validation set. Firstly, we constructed a signature in the training set by the least absolute shrinkage and selection operator penalized cox regression analysis and the multivariate cox regression analysis. Then, we validated the independent prognostic role of the risk signature in both training and validation set with survival analysis, receiver operating characteristic analysis, and Cox regression. The nomogram was established to demonstrate the predictive power of the signature. Moreover, high risk scores were significantly correlated to worse outcomes and severe clinical characteristics. The Pearson’s analysis between risk scores with immune cells infiltration, tumor mutation burden, and the expression level of chemotherapy target molecules indicated that the signature could predict efficacy of immunotherapy and targeted therapy. Next, we constructed an lncRNA–miRNA–mRNA regulatory network and identified several potential small molecule drugs in the Connectivity Map (CMap). What’s more, quantitative real-time PCR (qRT-PCR) analysis showed that serum LINC01559 could serve as a diagnostic biomarker. In vitro analysis showed inhibition of LINC01559 suppressed PC cell proliferation, migration, and invasion. Additionally, silencing LINC01559 suppressed gemcitabine-induced autophagy and promoted the sensitivity of PC cells to gemcitabine. In conclusion, we identified a novel ARlncRNAs signature with valuable clinical utility for reliable prognostic prediction and personalized treatment of PC patients. And inhibition of LINC01559 might be a novel strategy to overcome chemoresistance.

Bamboo is a natural fibre reinforced composite with excellent performance which is, to a certain extent, an alternative to the shortage of wood resources. The heterogeneous distribution and molecular structure of lignin is one of the factors that determines its performance, and it is the key and most difficult component in the basic research into the chemistry of bamboo and in bamboo processing and utilization. In this study, the distribution of lignin components and lignin content in micro-morphological regions were measured in semi-quantitative level by age and radial location by means of visible-light microspectrophotometry (VLMS) coupled with the Wiesner and Maule reaction. There as guaiacyl lignin and syringyl lignin in the cell wall of the fibre. Lignin content of the secondary cell wall and cell corner increased at about 10 days, reached a maximum at 1 year, and then decreased gradually. From 17 days to 4 years, the lignin content of the secondary cell wall in the outer part of bamboo is higher than that in the middle part (which is, in turn, higher than that in the inner part of the bamboo). VLSM results of the micro-morphological regions showed that bamboo lignification developed by aging. Guaiacyl and syringl lignin units can be found in the cell wall of the fibre, parenchyma, and vessel. There was a difference in lignin content among different ages, different radial location, and different micro-morphological regions of the cell wall. The fibre walls were rich in guaiacyl lignin in the early stage of lignification and rich in syringyl units in the later stage of lignification. The guaiacyl and syringyl lignin deposition of bamboo green was earlier than that of the middle part of bamboo culm, and that of the middle part of bamboo culm was earlier than that of bamboo yellow. The single molecule lignin content of the thin layer is higher than that of thick layers, while the primary wall is higher than the secondary cell wall, showing that lignin deposition is consistent with the rules of cell wall formation. The obtained cytological information is helpful to understand the origin of the anisotropic, physical, mechanical, chemical, and machining properties of bamboo.

Background: The accurate prediction of the tumor infiltration depth in the gastric wall based on enhanced CT images of gastric cancer is crucial for screening gastric cancer diseases and formulating treatment plans. Convolutional neural networks perform well in image segmentation. In this study, a convolutional neural network was used to construct a framework for automatic tumor recognition based on enhanced CT images of gastric cancer for the identification of lesion areas and the analysis and prediction of T staging of gastric cancer.Methods: Enhanced CT venous phase images of 225 patients with advanced gastric cancer from January 2017 to June 2018 were retrospectively collected. Ftable LabelImg software was used to identify the cancerous areas consistent with the postoperative pathological T stage. The training set images were enhanced to train the Faster RCNN detection model. Finally, the accuracy, specificity, recall rate, F1 index, ROC curve, and AUC were used to quantify the classification performance of T staging on this system.Results: The AUC of the Faster RCNN operating system was 0.93, and the recognition accuracies for T2, T3, and T4 were 90, 93, and 95%, respectively. The time required to automatically recognize a single image was 0.2 s, while the interpretation time of an imaging expert was ~10 s.Conclusion: In enhanced CT images of gastric cancer before treatment, the application of Faster RCNN to diagnosis the T stage of gastric cancer has high accuracy and feasibility.

The existence of residual lithium compounds (RLCs) on the surface of layered Ni-rich materials will deteriorate the electrochemical properties and cause safety problem. This work presents an effective surface washing method to remove the RLCs from LiNi0.90Co0.06Mn0.04O2 material surface, via ethyl alcohol solution that contains low concentration of boric acid. It is a low-cost process because the filter liquor can be recycled. The optimal parameters including washing time, boric acid concentration, and solid–liquid ratio were systematically studied. It has been determined by powder pH and Fourier transform infrared spectra results that the amount of RLCs was reduced effectively, and the storage performance was significantly enhanced for the washed samples. The 150th capacity retentions after storing had increased from 68.39% of pristine material to 85.46–94.84% of the washed materials. The performance enhancements should be ascribed to the surface washing process, which removed not only the RLCs, but also the loose primary particles effectively.

Electroencephalography (EEG) signal is an electrophysiological recording from electrodes placed on the scalp to reflect the electrical activities of the brain. Auditory brainstem response (ABR) is one type of EEG signals in response to an auditory stimulus, and it has been widely used to evaluate the potential disorders of the auditory function within the brain. Currently, the ABR measurements in the clinic usually adopt a fixed stimulation rate (FSR) technique in which the late evoked response could contaminate the ABR signals and deteriorate the waveform differentiation after averaging, thus compromising the overall auditory function assessment task. To resolve this issue, this study proposed a random stimulation rate (RSR) method by integrating a random interval between two adjacent stimuli. The results showed that the proposed RSR method was consistently repeatable and reliable in multiple trials of repeated measurements, and there was a large amplitude of successive late evoked response that would contaminate the ABR signals for conventional FSR methods. The ABR waveforms of the RSR method showed better wave I–V morphology across different stimulation rates and stimulus levels, and the improved ABR morphology played an important role in early diagnoses of auditory pathway abnormities. The correlation coefficients as functions of averaging time showed that the ABR waveform of the RSR method stabilizes significantly faster, and therefore, it could be used to speed up current ABR measurements with more reliable testing results. The study suggests that the proposed method would potentially aid the adequate reconstruction of ABR signals towards a more effective means of hearing loss screening, brain function diagnoses, and potential brain–computer interface.

(E)-N,N-dimethyl-4-oxo-4-(4-(pyridin-4-yl)phenyl)but-2-enamide hydrochloride (IMB-YH-4py5-2H) is a novel Protein Kinase B (PknB) inhibitor with potent activity against Mycobacterium tuberculosis strains. In the present study, a sensitive and specific liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine IMB-YH-4py5-2H in rat plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and separation was performed on an XTerra MS C18 column (2.1×50 mm, 3.5 μm) with gradient elution (methanol and 0.1% formic acid) at a flow rate of 0.3 mL/min. Detection was performed in multiple reaction monitoring (MRM) mode. Linear calibration curves were obtained over a concentration range of 1-100 ng/mL. The intra-day and inter-day precisions were lower than 8.46%, and the accuracies ranged from -8.71% to 12.36% at all quality control levels. The extraction recoveries were approximately 70%, and the matrix effects were negligible. All quality control samples were stable under different storage conditions. The validated method was successfully applied to a preclinical pharmacokinetic study in Sprague-Dawley rats. IMB-YH-4py5-2H demonstrated improved pharmacokinetic properties (higher exposure level) compared with its leading compound. IMB-YH-4py5-2H was also distributed throughout the lung pronouncedly, especially inside alveolar macrophages, indicating its effectiveness against lower respiratory infections.

ObjectiveThe aim of this study is to assess network-based weight loss interventions in the Chinese setting using agent-based simulation.MethodsAn agent-based model incorporating social, environmental and personal influence is developed to simulate the obesity epidemic through an interconnected social network among a population of 2197 individuals from the nationally representative survey. Model parameters are collected from literature and existing database. To ensure the robustness of our findings, the model is validated against empirical observations and sensitivity analyses are performed on calibrated parameters.ResultsWhen compared with the baseline model, significant weight difference is detected using paired samples t tests for network-based intervention strategies (p0.05). Targeting the most connected individuals minimizes the average population weight, average BMI, and generates a reduction of 2.70% and 1.38% in overweight and obesity prevalence.ConclusionsThe simulations shows that targeting individuals on the basis of their social network attributes outperforms conventional targeting strategies. Future work needs to focus on how to further leverage social networks to curb obesity prevalence and enhance interventions for other chronic conditions using agent-based simulation.

Measures of predictability in physiological signals based on entropy metrics have been widely used in the application domain of medical assessment and clinical diagnosis. In this paper, we propose a new entropy-based pattern learning by a combination of singular spectrum analysis (SSA) and entropy measures for assessment of physiological signals. Physiological signals are first represented as a series of SSA components, and then well-established entropy measures are extracted from the resulting SSA components that can help to facilitate the features extraction from physiological signals. The entropy measures of notable SSA components are used to form input features and fed into pattern classifier. To demonstrate its validity, applicability, and versatility, the proposed entropy-based pattern learning is used to perform medical assessments with three kinds of classical physiological signals, that is, electroencephalogram (EEG), electromyogram (EMG), and RR-interval signals. Experiments demonstrate that in all cases, the proposed entropy-based pattern learning can effectively capture specific biosignal patterns of physiological signals and achieve excellent identification performances for the assessments of EEG, EMG, and RR-interval signals. Besides, through the comparison of the identification performances for entropy-based pattern learning based on the physiological signals themselves and the SSA components, it is concluded that the discriminating power of entropy-based pattern learning based on the SSA components is much stronger than that based on the physiological signals themselves. Since it can be easily extended to any other physiological signal analysis, the proposed entropy-based pattern learning may use as an efficient approach to reveal biosignal patterns for medical assessment of physiological signals.

In the study, in order to completely utilize the advantages of graphene monolayer, nano-fibrillated cellulose with cations from polyethyleneimine (PEI) was used as the intercalator to efficiently exfoliate the reduced graphene oxide into a single layer with a thickness about 0.47 nm by means of ionic attraction. After the high-temperature treatment (800 °C), the carbon aerogel (NC-GO@NFC) with an architectural structure was manufactured by combining 2D monolayer graphene with 1D nano-fibrillated cellulose. The pore volume (0.55 cm3/g) and specific surface area (441 m2/g) of NC-GO@NFC were about two times higher than those of GO carbon aerogel. Particularly, the buoyant porous aerogel showed superhydrophobicity with a large water contact angle (155.5°) due to the increase of -NH- and CC as well as the pyrolysis of hydrophilic groups. The superhydrophobicity endows the aerogel with an exceptional oil/water separation performance. The carbon aerogels exhibited the adsorption capability towards many organic phases (including lubricating oil and some organic solvents). In addition, the efficient continuous removal and collection of organic solvents (methylbenzene) from water surface was achieved by a designed water/oil pump device. Therefore, the recyclable 3D porous composite aerogel had the application potential as organic solvent adsorbents and oil/water separation agents. Keywords: Exfoliated graphene, Superhydrophobic, Sorbent, Carbonization, Nano-fibrillated cellulose, Graphene

Establishing biosensors to map a comprehensive picture of potential estrogen-active chemicals remains challenging and must be addressed. Herein, we describe an estrogen receptor (ER)-based evanescent wave fluorescent biosensor by using a triple functional small-molecule–protein conjugate as a signal probe for the determination of estrogenic activities in water samples. The signal probe, consisting of a Cy5.5-labelled streptavidin (STV) moiety and a 17β-estradiol (E2) moiety, acts simultaneously as signal conversion, signal recognition and signal report elements. When xenoestrogens compete with the E2 moiety of conjugate in binding to the ER, the unbound conjugates are released, and their STV moiety binds with desthiobiotin (DTB) modified on the optical fiber via the STV–DTB affinity interactions. Signal probe detection is accomplished by fluorescence emission induced by an evanescent field, which positively relates with the estrogenic activities in samples. Quantification of estrogenic activity expressed as E2 equivalent concentration (EEQ) can be achieved with a detection limit of 1.05 μg/L EEQ by using three times standard deviation of the mean blank values and a linear calibration range from 20.8 to 476.7 μg/L EEQ. The optical fiber system is robust enough for hundreds of sensing cycles. The biosensor-based determination of estrogenic activities in wastewater samples obtained from a full-scale wastewater treatment plant is consistent with that measured by the two-hybrid recombinant yeast bioassay. Keywords: Estrogen receptor, Small-molecule–protein conjugate, Optical fiber biosensor, 17β-estradiol equivalent concentration, Wastewater sample

ObjectivesExamination of the prevalence and patterns of multimorbidity among the elderly in China.DesignCross-sectional study.SettingMore than 10 000 households in 28 of the 34 provinces of mainland China.Participants11 707 Chinese adults aged 60 and over.Primary outcome measuresPrevalence and patterns of multimorbidity among the participants. Relative risks were calculated to estimate the probability of up to 14 chronic conditions coexisting with each other. Observed-to-expected (O/E) ratios were used to analyse the patterns of multimorbidity.ResultsMultimorbidity was present in 43.6% of respondents from the sample population, with women having the greater prevalence compared with men. There were 804 different comorbidity combinations identified, including 76 dyad combinations and 169 triad combinations. The top 10 morbidity dyads and triads accounted for 69.01% and 47.05% of the total dyad and triad combinations observed, respectively. Among the 14 chronic conditions included in the study, asthma, stroke, heart attack and six other chronic conditions were the main components of multimorbidity due to their high relative risk ratios. The most frequently occurring clusters with higher O/E ratios were stroke along with emotional, nervous, or psychiatric problems; memory-related diseases together emotional, nervous, or psychiatric problems; and memory-related diseases and asthma accompanied by chronic lung diseases and asthma.ConclusionsThe results of this study highlight the high prevalence of multimorbidity in the elderly population in China. Further studies are required to understand the aetiology of multimorbidity, and future primary healthcare policies should be made while taking multimorbidity into consideration.

Abstract Background The correlation between the atherogenic index of plasma (AIP) and waist circumference (WC) remains unknown. Methods A total of 5351 middle-aged men living in Southeastern China were surveyed using the random stratified cluster sampling method. A WC of 90 cm or greater was indicative of abdominal obesity, and AIP was calculated as follows: log [triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C)]. Results (1) A significantly higher AIP was observed in subjects with abdominal obesity than in those without abdominal obesity (P 0·21), WC was >90 cm. Conclusions AIP of 0·12–0·21 or >0·21 indicates a likelihood of borderline abdominal obesity or abdominal obesity, respectively, and the combination of WC and AIP may increase the specificity and sensitivity for detection of abdominal obesity in clinical practice. The results suggest that AIP may be used as a reference to estimate abdominal obesity.

It is well known that there may be significant individual differences in physiological signal patterns for emotional responses. Emotion recognition based on electroencephalogram (EEG) signals is still a challenging task in the context of developing an individual-independent recognition method. In our paper, from the perspective of spatial topology and temporal information of brain emotional patterns in an EEG, we exploit complex networks to characterize EEG signals to effectively extract EEG information for emotion recognition. First, we exploit visibility graphs to construct complex networks from EEG signals. Then, two kinds of network entropy measures (nodal degree entropy and clustering coefficient entropy) are calculated. By applying the AUC method, the effective features are input into the SVM classifier to perform emotion recognition across subjects. The experiment results showed that, for the EEG signals of 62 channels, the features of 18 channels selected by AUC were significant (p < 0.005). For the classification of positive and negative emotions, the average recognition rate was 87.26%; for the classification of positive, negative, and neutral emotions, the average recognition rate was 68.44%. Our method improves mean accuracy by an average of 2.28% compared with other existing methods. Our results fully demonstrate that a more accurate recognition of emotional EEG signals can be achieved relative to the available relevant studies, indicating that our method can provide more generalizability in practical use.

Since its founding in 2013, the Kutztown University Association for Women in Mathematics student chapter has built a supportive community of women students and faculty on campus and beyond. This article aims to share our successful experiences with the broader community by presenting our pre- and mid-pandemic AWM activities including Mathematics Day for Girls, Women's Empowerment Day, Beyond Pink-Collar Jobs, and our Kutztown University AWM Virtual Lecture Series. Feedback from past and current participants of our AWM student chapter is also included.

In the conventional straw returning operation, the maize straw is broken into pieces of about 10 cm and degraded naturally in the farmland. Under the conventional straw returning mode, maize straw does not easily decompose quickly in cold climate conditions, which can cause a significant decrease in the dry matter accumulation rate of next maize seedlings. Therefore, it is difficult to popularize conventional straw returning in the maize-growing regions of Northeast China. In order to solve the above-mentioned problems, a new agronomic technology of straw returning is proposed in this study, and a corresponding Bionic Straw Fine Crusher is developed to match the agronomic requirements. The key function of fine-crush straw returning is to significantly increase the contact area between the straw pith and the external environment by significantly shortening the crushing length, thus accelerating the rate of straw decomposition. In this study, the differences in operational effects between fine-crush straw returning, conventional straw returning, and no returning are clarified through 6 consecutive years of field experiments. At the same time, statistical analysis of the experimental data reveals the influence of fine-crush straw returning on the dry matter accumulation of maize at the seedling stage under the conditions of different returning modes, and determines the optimal agronomic parameter combination. The results of this study show that fine-crush straw returning significantly increased the decomposition rate, soil organic matter content, and soil accumulated temperature, thus creating a seedbed more favorable for maize seedling development. The experimental results showed that the optimal crushing length values of fine-crush straw returning were 1.5 cm, 3 cm, and 1.5 cm under mulching returning, shallow burial returning, and deep tillage returning conditions, respectively. Compared with conventional straw returning and no returning operations, the fine-crush straw returning operation can increase the maximum seedling dry matter accumulation of the maize crop by 5.1 g/plant and 2.8 g/plant (shallow burial), 4.2 g/plant and 1.8 g/plant (deep tillage), and 4.3 g/plant and 1.9 g/plant (mulching returning). The findings of this study may provide a viable new agronomic technology to accelerate the spread of straw returning in maize-growing areas of Northeast China.

Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [89Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [18F]-fluorodeoxyglucose ([18F]-FDG) PET/CT imaging. Spearman’s correlation, Kendall’s tau, Kolmogorov–Smirnov test, and ANOVA were used for statistical analysis. [89Zr]-pertuzumab mean standard uptake values (SUVmean) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2−) tumors were 1.1 ± 0.4. [18F]-FDG SUVmean changes were negatively correlated with [89Zr]-pertuzumab SUVmean (r = −0.5887, p = 0.0030). The baseline [18F]-FDG SUVmean was negatively correlated with initial [89Zr]-pertuzumab SUVmean (r = −0.6852, p = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.

Abstract Nanofibrillated chitin/Ag2O aerogels were fabricated for radioiodine removal. Chitin was first fabricated into nanofibers with abundant acetyl amino groups (–NHCOCH3) on the surface. Then, highly porous chitin nanofiber (ChNF) aerogels were obtained via freeze-drying. The ChNF aerogels exhibited a low bulk density of 2.19 mg/cm3 and a high specific surface area of 179.71 m2/g. Ag2O nanoparticles were evenly anchored on the surfaces of ChNF scaffolds via strong interactions with –NHCOCH3 groups, subsequently yielding Ag2O@ChNF heterostructured aerogels. The composites were used as efficient absorbents to remove radioiodine anions from water and capture a high amount of I2 vapor in the forms of AgI and iodine molecules. The adsorption capacity of the composite monoliths can reach up to 2.81 mmol/g of I− anions. The high adsorbability of the composite monolithic aerogel signifies its potential applications in radioactive waste disposal.

Background/Aims: Circulating tumor cells (CTCs) are valuable in both basic research and clinical application for cancer management. In the current study, we evaluated the diagnostic value of CTCs in pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 143 blood samples from 95 consecutively diagnosed PDAC patients and 48 healthy donors were collected. Combined data from immunostaining of CD45, DAPI and fluorescence in situ hybridization (FISH) with chromosome 8 centromere (CEP8) probe were used to identify CTCs. Cells with features of CD45-/DAPI+/CEP8>2 were detected as CTCs. Results: CTCs were classified as triploid, tetraploid and multiploid based on chromosome 8 copy number. CTC subtype composition was significantly different among groups. Both subtype number and total CTC number were significantly increased in PDAC patients, compared to healthy controls. Total CTC number had 75.8% sensitivity and 68.7% specificity at a cutoff value of 2 cells/3.2 mL. This study is the first to report that CTC subtype number is also useful in cancer diagnosis. Sensitivity was 53.7% and specificity was 85.4% at a cutoff point of 2 CTC subtypes. The diagnostic value of both total CTC number and CTC subtype number was a little poorer than CA199. Conclusions: Both CTC subtype and total CTC number may serve as potential biomarkers for PDAC.

Osteoclasts are bone resorptive cells and an attractive target to treat diseases characterized by excessive bone loss, but little is known about osteoclast inhibition. Here the authors identify Gα13 as an intracellular inhibitor of osteoclastogenesis that can prevent bone loss in mice via Akt activation and inhibition of RhoA signalling.

Background: Chronic intermittent hypoxia is the most remarkable feature of obstructive sleep apnea/hypopnea syndrome and it can induce the change of hypoxia-inducible factor-1α (HIF-1α) expression and contractile properties in the genioglossus. To clarify the role of HIF-1α in contractile properties of the genioglossus, this study generated and compared high-throughput RNA-sequencing data from genioglossus between HIF-1α conditional knockout (KO) mice and littermate wild-type (WT) mice. Methods: KO mice were generated with cre-loxP strategy. Gene expression profile analysis was performed using gene enrichment analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differently expressed messenger RNAs were performed to identify the related pathways and biological functions. Six differentially expressed genes (DEGs) were validated by qualitative reverse transcription polymerase chain reaction. Results: A total of 142 (77 upregulated and 65 downregulated) transcripts were found to exhibit statistically significant difference between the HIF-1α-KO and WT mice. GO and KEGG analyses indicated that DEGs included genes involved in “skeletal muscle cell differentiation,” “muscle organ development,” “glucose metabolic process,” “glycogen biosynthetic and metabolic process,” etc. Conclusion: This study might provide evidence that HIF-1α affects the expression of multiple genes involved in the myogenesis, muscle development, and carbohydrate metabolism through transcriptome analysis in conditional HIF-1α-KO mice.

Hot tearing is often a major casting defect in magnesium alloys and has a significant impact on the quality of their casting products. Hot tearing of magnesium alloys is a complex solidification phenomenon which is still not fully understood, it is of great importance to investigate the hot tearing behaviour of magnesium alloys. This review attempts to summarize the investigations on hot tearing of magnesium alloys over the past decades. The hot tearing criteria including recently developed Kou's criterion are summarized and compared. The numeric simulation and assessing methods of hot tearing, factors influencing hot tearing, and hot tearing susceptibility (HTS) of magnesium alloys are discussed.

Rheumatoid arthritis (RA) is a common autoimmune disease linked to chronic inflammation. Dysbiosis of the gut microbiota has been proposed to contribute to the risk of RA, and a large number of researchers have investigated the gut-joint axis hypothesis using the collagen-induced arthritis (CIA) rats. However, previous studies mainly involved short-term experiments; very few used the CIA model to investigate changes in gut microbiota over time. Moreover, previous research failed to use the CIA model to carry out detailed investigations of the effects of drug treatments upon inflammation in the joints, hyperplasia of the synovium, imbalance in the ratios of Th1/Th2 and Th17/Treg cells, intestinal cytokines and the gut microbiota following long-term intervention. In the present study, we carried out a 16-week experiment to investigate changes in the gut microbiota of CIA rats, and evaluated the modulatory effect of total glucosides of paeony (TGP), an immunomodulatory agent widely used in the treatment of RA, after 12 weeks of administration. We found that taxonomic differences developed in the microbial structure between the CIA group and the Control group. Furthermore, the administration of TGP was able to correct 78% of these taxonomic differences, while also increase the relative abundance of certain forms of beneficial symbiotic bacteria. By the end of the experiment, TGP had reduced body weight, thymus index and inflammatory cell infiltration in the ankle joint of CIA rats. Furthermore, the administration of TGP had down-regulated the synovial content of VEGF and the levels of Th1 cells and Th17 cells in CIA rats, and up-regulated the levels of Th2 cells and Treg cells. The administration of TGP also inhibited the levels of intestinal cytokines, secretory immunoglobulin A (SIgA) and Interferon-γ (IFN-γ). In conclusion, the influence of TGP on dynamic changes in gut microbiota, along with the observed improvement of indicators related to CIA symptoms during 12 weeks of administration, supported the hypothesis that the microbiome may play a role in TGP-mediated therapeutic effects in CIA rats. The present study also indicated that the mechanism underlying these effects may be related to the regulation of intestinal mucosal immunity remains unknown and deserves further research attention.