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Background: Metagenomic next-generation sequencing (mNGS) is an emerging technique for the clinical diagnosis of infectious disease that has rarely been used for the diagnosis of ascites infection in patients with cirrhosis. This study compared mNGS detection with conventional culture methods for the on etiological diagnosis of cirrhotic ascites and evaluated the clinical effect of mNGS. Methods: A total of 109 patients with ascites due to cirrhosis were included in the study. We compared mNGS with conventional culture detection by analyzing the diagnostic results, pathogen species and clinical effects. The influence of mNGS on the diagnosis and management of ascites infection in patients with cirrhosis was also evaluated. Results: Ascites cases were classified into three types: spontaneous bacterial peritonitis (SBP) (16/109, 14.7%), bacterascites (21/109, 19.3%) and sterile ascites (72/109, 66.1%). In addition, 109 patients were assigned to the ascites mNGS-positive group (80/109, 73.4%) or ascites mNGS-negative group (29/109, 26.6%). The percentage of positive mNGS results was significantly greater than that of traditional methods (73.4% vs. 28.4%, P < 0.001). mNGS detected 43 strains of bacteria, 9 strains of fungi and 8 strains of viruses. Fourteen bacterial strains and 3 fungal strains were detected via culture methods. Mycobacteria, viruses, and pneumocystis were detected only by the mNGS method. The mNGS assay produced a greater polymicrobial infection rate than the culture method (55% vs. 16%). Considering the polymorphonuclear neutrophil (PMN) counts, the overall percentage of pathogens detected by the two methods was comparable, with 87.5% (14/16) in the PMN ≥ 250/mm3 group and 72.0% (67/93) in the PMN < 250/mm3 group (P > 0.05). Based on the ascites PMN counts combined with the mNGS assay, 72 patients (66.1%) were diagnosed with ascitic fluid infection (AFI) (including SBP and bacterascites), whereas based on the ascites PMN counts combined with the culture assay, 37 patients (33.9%) were diagnosed with AFI (P < 0.05). In 60 (55.0%) patients, the mNGS assay produced positive clinical effects; 40 (85.7%) patients had their treatment regimen adjusted, and 48 patients were improved. The coincidence rate of the mNGS results and clinical findings was 75.0% (60/80). Conclusions: Compared with conventional culture methods, mNGS can improve the detection rate of ascites pathogens, including bacteria, viruses, and fungi, and has significant advantages in the diagnosis of rare pathogens and pathogens that are difficult to culture; moreover, mNGS may be an effective method for improving the diagnosis of ascites infection in patients with cirrhosis, guiding early antibiotic therapy, and for reducing complications related to abdominal infection. In addition, explaining mNGS results will be challenging, especially for guiding the treatment of infectious diseases. [ABSTRACT FROM AUTHOR]

Background: Autistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging perspectives. Methods: We used the Autism Spectrum Screening Questionnaire (ASSQ) to assess and define subjects with and without ATs. For behavioral analyses, 67 children with ADHD and ATs (ADHD + ATs), 105 children with ADHD but without ATs (ADHD − ATs), and 44 typically developing healthy controls without ATs (HC − ATs) were recruited. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the mean amplitude of low-frequency fluctuation (mALFF) values (an approach used to depict different spontaneous brain activities) in a sub-sample. The imaging features that were shared between ATs and ADHD symptoms or that were unique to one or the other set of symptoms were illustrated as a way to explore the "brain–behavior" relationship. Results: Compared to ADHD-ATs, the ADHD + ATs group showed more global impairment in all aspects of autistic symptoms and higher hyperactivity/impulsivity (HI). Partial-correlation analysis indicated that HI was significantly positively correlated with all aspects of ATs in ADHD. Imaging analyses indicated that mALFF values in the left middle occipital gyrus (MOG), left parietal lobe (PL)/precuneus, and left middle temporal gyrus (MTG) might be specifically related to ADHD, while those in the right MTG might be more closely associated with ATs. Furthermore, altered mALFF in the right PL/precuneus correlated with both ADHD and ATs, albeit in diverse directions. Conclusions: The co-occurrence of ATs in children with ADHD manifested as different behavioral characteristics and specific brain functional alterations. Assessing ATs in children with ADHD could help us understand the heterogeneity of ADHD, further explore its pathogenesis, and promote clinical interventions. [ABSTRACT FROM AUTHOR]

Background: Two types of non-invasive, radiation-free, and inexpensive imaging technologies that are widely employed in medical applications are ultrasound (US) and infrared thermography (IRT). The ultrasound image obtained by ultrasound imaging primarily expresses the size, shape, contour boundary, echo, and other morphological information of the lesion, while the infrared thermal image obtained by infrared thermography imaging primarily describes its thermodynamic function information. Although distinguishing between benign and malignant thyroid nodules requires both morphological and functional information, present deep learning models are only based on US images, making it possible that some malignant nodules with insignificant morphological changes but significant functional changes will go undetected. Results: Given the US and IRT images present thyroid nodules through distinct modalities, we proposed an Adaptive multi-modal Hybrid (AmmH) classification model that can leverage the amalgamation of these two image types to achieve superior classification performance. The AmmH approach involves the construction of a hybrid single-modal encoder module for each modal data, which facilitates the extraction of both local and global features by integrating a CNN module and a Transformer module. The extracted features from the two modalities are then weighted adaptively using an adaptive modality-weight generation network and fused using an adaptive cross-modal encoder module. The fused features are subsequently utilized for the classification of thyroid nodules through the use of MLP. On the collected dataset, our AmmH model respectively achieved 97.17% and 97.38% of F1 and F2 scores, which significantly outperformed the single-modal models. The results of four ablation experiments further show the superiority of our proposed method. Conclusions: The proposed multi-modal model extracts features from various modal images, thereby enhancing the comprehensiveness of thyroid nodules descriptions. The adaptive modality-weight generation network enables adaptive attention to different modalities, facilitating the fusion of features using adaptive weights through the adaptive cross-modal encoder. Consequently, the model has demonstrated promising classification performance, indicating its potential as a non-invasive, radiation-free, and cost-effective screening tool for distinguishing between benign and malignant thyroid nodules. The source code is available at https://github.com/wuliZN2020/AmmH. [ABSTRACT FROM AUTHOR]

Background: Two important flavonoids, kaempferol and quercetin possess remarkably potent biological impacts on human health. However, their structural complexity and low abundance in nature make both bulk chemical synthesis and extraction from native plants difficult. Therefore microbial production via heterologous expression of plant enzymes can be a safe and sustainable route for their production. Despite several attempts reported in microbial hosts, the production levels of kaempferol and quercetin still stay far behind compared to many other microbial-produced flavonoids. Results: In this study, Saccharomyces cerevisiae was engineered for high production of kaempferol and quercetin in minimal media from glucose. First, the kaempferol biosynthetic pathway was reconstructed via screening various F3H and FLS enzymes. In addition, we demonstrated that amplification of the rate-limiting enzyme AtFLS could reduce the dihydrokaempferol accumulation and improve kaempferol production. Increasing the availability of precursor malonyl-CoA further improved the production of kaempferol and quercetin. Furthermore, the highest amount of 956 mg L− 1 of kaempferol and 930 mg L− 1 of quercetin in yeast was reached in fed-batch fermentations. Conclusions: De novo biosynthesis of kaempferol and quercetin in yeast was improved through increasing the upstream naringenin biosynthesis and debugging the flux-limiting enzymes together with fed-batch fermentations, up to gram per liter level. Our work provides a promising platform for sustainable and scalable production of kaempferol, quercetin and compounds derived thereof. [ABSTRACT FROM AUTHOR]

Background: The antiphagocytic molecule CD47 is overexpressed in a wide variety of cancer cells, and antibodies targeting CD47 for cancer therapies are currently under intensive investigation. However, owing to the ubiquitous expression of CD47 on healthy cells, anti-CD47 therapies often achieve only weak therapeutic benefits and can induce severe side effects. Here, we report the generation of a pH-dependent anti-CD47 antibody (BC31M4) which selectively binds to tumors under the acidic solid tumor microenvironment. Methods: BC31M4 was generated using antibody phage display and a pH-dependent selection strategy. The pH-dependent binding and blocking activities of BC31M4 were verified using in vitro assays, and the structural basis of the pH-dependent binding property was characterized. BC31M4's antitumor effect was confirmed by both phagocytosis assays and studies in xenograft models. The tumor selectivity, mechanism of action, PK properties, side effects, and therapeutic efficacy were further evaluated in humanized (hCD47 and its receptor hSIRPα) immunocompetent syngeneic mouse models. Results: The crystal structure reveals that two histidines locate within the CDRs of the light chain directly contribute to the pH-dependent binding of BC31M4. BC31M4 promotes macrophage phagocytosis of tumor cells more potently at acidic-pH than at physiological-pH. Our hCD47/hSIRPα humanized syngeneic mouse model results demonstrated that BC31M4 selectively accumulates in tumors but not in normal tissues. BC31M4 causes minimal side effects and exhibits superior PK properties as compared to the other examined anti-CD47 antibodies. When combined with adoptive T cell transfer, BC31M4 efficiently promotes adaptive immune responses against tumors and also induces immune memory. Moreover, we show that BC31M4's antitumor effects rely on an Fc that mediates strong effector functions. Conclusions: Our study illustrates that the development of a tumor-selective, pH-dependent anti-CD47 antibody safely confers strong therapeutic effects against solid tumors, thus providing a promising therapeutic strategy to overcome the challenges of anti-CD47 therapy. [ABSTRACT FROM AUTHOR]

Purpose: CT ventilation image (CTVI)-guided radiotherapy that selectively avoids irradiating highly-functional lung regions has potential to reduce pulmonary toxicity. Considering Helical TomoTherapy (HT) has higher modulation capabilities, we investigated the capability and characteristic of HT at sparing functional lungs for locally advanced lung cancer. Methods and materials: Pretreatment 4DCT scans were carried out for 17 patients. Local lung volume expansion (or contraction) during inspiration is related to the volume change at a given lung voxel and is used as a surrogate for ventilation. The ventilation maps were generated from two sets of CT images (peak-exhale and peak-inhale) by deformable registration and a Jacobian-based algorithm. Each ventilation map was normalized to percentile images. Six plans were designed for each patient: one anatomical plan without ventilation map and five functional plans incorporating ventilation map which designed to spare varying degrees of high-functional lungs that were defined as the top 10%, 20%, 30%, 40%, and 50% of the percentile ventilation ranges, respectively. The dosimetric and evaluation factors were recorded regarding planning target volume (PTV) and other organs at risk (OARs), with particular attention to the dose delivered to total lung and functional lungs. An established dose-function-based normal tissue complication probability (NTCP) model was used to estimate risk of radiation pneumonitis (RP) for each scenario. Results: Patients were divided into a benefit group (8 patients) and a non-benefit group (9 patients) based on whether the RP-risk of functional plan was lower than that of anatomical plan. The distance between high-ventilated region and PTV, as well as tumor volume had significant differences between the two groups (P < 0.05). For patients in the benefit group, the mean value of fV5, fV10, fV20, and fMLD (functional V5, V10, V20, and mean lung dose, respectively) were significantly lower starting from top 30% functional plan than in anatomical plan (P < 0.05). With expand of avoidance region in functional plans, the dose coverage of PTV is not sacrificed (P > 0.05) but at the cost of increased dose received by OARs. Conclusion: Ventilation image-guided HT plans can reduce the dose received by highly-functional lung regions with a range up to top 50% ventilated area. The spatial distribution of ventilation and tumor size were critical factors to better select patients who could benefit from the functional plan. [ABSTRACT FROM AUTHOR]

Background: Moral courage as part of the moral competence of nurses has received increasing attention. Determination of the factors affecting moral courage is important in improving the quality of care. The purpose of this study was to investigate moral courage and related factors among frontline nurses from an empowerment perspective. Methods: A cross-sectional study was conducted using data collection instruments comprising four main parts: the self-designed form of demographic characteristics, Conditions for Work Effectiveness II (CWEQ-II), Spreitzer's Psychological Empowerment Scale (PES) and Nurses' Moral Courage Scale (NMCS). Data were collected from 226 nurses in a tertiary hospital between February and March 2022 in Wuhan, the capital city of Hubei Province in central China. Descriptive statistics and multiple linear regression were used to analyze the data. Results: The means of the total scores for the CWEQ-II, PES and the NMCS were 3.52 (SD = 0.69), 3.85 (SD = 0.53) and 3.90 (SD = 0.67), respectively. All the dimensions and the total scores of the CWEQ-II and PES were significantly correlated with the NMCS (p < 0.001). According to the multivariate stepwise regression analysis, CWEQ-II and PES were determined to be factors affecting NMCS. These variables explained 35.9% of the total variance in the moral courage scores of nurses. Conclusion: The level of moral courage among nurses is above average. Structural empowerment and psychological empowerment were the key factors affecting the promotion of moral courage. Hospital and organizational administrations should be conscious of the role of attach structural empowerment and psychological empowerment in the nursing workplace in increasing moral courage. [ABSTRACT FROM AUTHOR]

Background: Making clear what kinds of metabolic pathways a drug compound involves in can help researchers understand how the drug is absorbed, distributed, metabolized, and excreted. The characteristics of a compound such as structure, composition and so on directly determine the metabolic pathways it participates in. Methods: We developed a novel hybrid framework based on the graph attention network (GAT) to predict the metabolic pathway classes that a compound involves in, named HFGAT, by making use of its global and local characteristics. The framework mainly consists of a two-branch feature extracting layer and a fully connected (FC) layer. In the two-branch feature extracting layer, one branch is responsible to extract global features of the compound; and the other branch introduces a GAT consisting of two graph attention layers to extract local structural features of the compound. Both the global and the local features of the compound are then integrated into the FC layer which outputs the predicted result of metabolic pathway categories that the compound belongs to. Results: We compared the multi-class classification performance of HFGAT with six other representative methods, including five classic machine learning methods and one graph convolutional network (GCN) based deep learning method, on the benchmark dataset containing 6999 compounds belonging to 11 pathway categories. The results showed that the deep learning-based methods (HFGAT, GCN-based method) outperformed the traditional machine learning methods in the prediction of metabolic pathways and our proposed HFGAT method performed better than the GCN-based method. Moreover, HFGAT achieved higher F 1 scores on 8 of 11 classes than the GCN-based method. Conclusions: Our proposed HFGAT makes use of both the global and local information of the compounds to predict their metabolic pathway categories and has achieved a significant performance. Compared with the GCN model, the introduction of the GAT can help our model pay more attention to substructures of the compound that are useful for the prediction task. The study provided a potential method for drug discovery with all types of metabolic reactions that may be involved in the decomposition and synthesis of pharmaceutical compounds in the organism. [ABSTRACT FROM AUTHOR]

Background: Retrosynthesis prediction is the task of deducing reactants from reaction products, which is of great importance for designing the synthesis routes of the target products. The product molecules are generally represented with some descriptors such as simplified molecular input line entry specification (SMILES) or molecular fingerprints in order to build the prediction models. However, most of the existing models utilize only one molecular descriptor and simply consider the molecular descriptors in a whole rather than further mining multi-scale features, which cannot fully and finely utilizes molecules and molecular descriptors features. Results: We propose a novel model to address the above concerns. Firstly, we build a new convolutional neural network (CNN) based feature extraction network to extract multi-scale features from the molecular descriptors by utilizing several filters with different sizes. Then, we utilize a two-branch feature extraction layer to fusion the multi-scale features of several molecular descriptors to perform the retrosynthesis prediction without expert knowledge. The comparing result with other models on the benchmark USPTO-50k chemical dataset shows that our model surpasses the state-of-the-art model by 7.4%, 10.8%, 11.7% and 12.2% in terms of the top-1, top-3, top-5 and top-10 accuracies. Since there is no related work in the field of bioretrosynthesis prediction due to the fact that compounds in metabolic reactions are much more difficult to be featured than those in chemical reactions, we further test the feasibility of our model in task of bioretrosynthesis prediction by using the well-known MetaNetX metabolic dataset, and achieve top-1, top-3, top-5 and top-10 accuracies of 45.2%, 67.0%, 73.6% and 82.2%, respectively. Conclusion: The comparison result on USPTO-50k indicates that our proposed model surpasses the existing state-of-the-art model. The evaluation result on MetaNetX dataset indicates that the models used for retrosynthesis prediction can also be used for bioretrosynthesis prediction. [ABSTRACT FROM AUTHOR]

Background: Via counting the different kinds of white blood cells (WBCs), a good quantitative description of a person's health status is obtained, thus forming the critical aspects for the early treatment of several diseases. Thereby, correct classification of WBCs is crucial. Unfortunately, the manual microscopic evaluation is complicated, time-consuming, and subjective, so its statistical reliability becomes limited. Hence, the automatic and accurate identification of WBCs is of great benefit. However, the similarity between WBC samples and the imbalance and insufficiency of samples in the field of medical computer vision bring challenges to intelligent and accurate classification of WBCs. To tackle these challenges, this study proposes a deep learning framework by coupling the pre-trained ResNet and DenseNet with SCAM (spatial and channel attention module) for accurately classifying WBCs. Results: In the proposed network, ResNet and DenseNet enables information reusage and new information exploration, respectively, which are both important and compatible for learning good representations. Meanwhile, the SCAM module sequentially infers attention maps from two separate dimensions of space and channel to emphasize important information or suppress unnecessary information, further enhancing the representation power of our model for WBCs to overcome the limitation of sample similarity. Moreover, the data augmentation and transfer learning techniques are used to handle the data of imbalance and insufficiency. In addition, the mixup approach is adopted for modeling the vicinity relation across training samples of different categories to increase the generalizability of the model. By comparing with five representative networks on our developed LDWBC dataset and the publicly available LISC, BCCD, and Raabin WBC datasets, our model achieves the best overall performance. We also implement the occlusion testing by the gradient-weighted class activation mapping (Grad-CAM) algorithm to improve the interpretability of our model. Conclusion: The proposed method has great potential for application in intelligent and accurate classification of WBCs. [ABSTRACT FROM AUTHOR]

Background: Diabetes and impaired glucose regulation are very common in patients with coronary artery disease (CAD). In this study, we aim to investigate the prevalence of abnormal glucose regulation in men and women in Chinese CAD patients.Methods: In this retrospective study, 4100 patients (male, n = 2873; female, n = 1227)with CAD were enrolled. The mean age of these patients was 63 years. The demographic data, medical history, echocardiography findings and blood investigations were collected and analyzed.Results: In this population, 953 (24%) patients had definite diagnosis of type 2 diabetes mellitus, including 636 males (23%) and 317 females (27%). There was a higher prevalence of diabetes in females than men (p < 0.05). For the remaining patients, 48% (n = 959) undergone an oral glucose tolerance test (OGTT), which revealed that 83 male patients (12%) and 41 female patients (16%) suffered from the type 2 diabetes (p > 0.05). 283 men (40%) and 105 women (41%) had impaired glucose regulation (IGR) (p > 0.05). Only 338 men (25%) and 109 women (19%) showed the normal glucose regulation, implying a higher prevalence of abnormal glucose regulation in females (p < 0.01). The odd ratio (OR) showed that women were more prone to have diabetes mellitus or IGT than men and the OR was 1.44 and 1.43 respectively.Conclusion: Abnormal glucose regulation is highly prevalent in CAD patients. The women are more prone to have diabetes mellitus or IGT than men. [ABSTRACT FROM AUTHOR]

Background: Shortcoming of traditional Nuss operation on adults is gradually found in the clinical practice. A new kind of introducer-bar complex was introduced. However, there is limited evidence regarding its safety and efficacy. Therefore, a single center, retrospective study was conducted to address this issue.Methods: Patients with pectus excavatum who underwent surgery between January 2015 and June 2017 were consecutively enrolled in this study. In all, 52 patients underwent the modified procedure using the introducer-bar complex (new procedure group), whereas 48 underwent the traditional anti-Nuss procedure (traditional procedure group). Outcomes analysis of balanced baseline was performed to compare the intraoperative and postoperative short-term outcomes.Results: All patients in the new procedure group had shorter operation duration (51.54 ± 20.32 vs. 79.45 ± 13.88 min, p = 0.017), postoperative hospitalizations (4.77 ± 1.62 vs. 6.86 ± 2.18 days, p = 0.028), plate removal surgery durations (39.30 ± 8.97 vs. 60.30 ± 10.49 min, p < 0.001), and less blood loss during operation (6.25 ± 4.88 vs. 10.90 ± 5.75 ml, p = 0.003) than patients in the traditional procedure group. There was no significant difference in the length of incision, postoperative Haller index, cost, number of steel bars, postoperative surgical outcome and incidence of complications between the two groups.Conclusion: Through the main clinical outcome were similar, our results shown that modified procedure may have the shorter operation time, postoperative hospital stay, and operation time for plate removal and less blood loss, which may bring potential clinical benefits to patients. [ABSTRACT FROM AUTHOR]

Background: Intermittent or prolonged exposure to severe cold stress disturbs energy homeostasis and can lead to hypothermia, heart failure, Alzheimer's disease, and so on. As the typical "hot" traditional Chinese medicine, Aconite has been widely used to treat cold-associated diseases for thousands of years, but its critical mechanisms for the promotion of thermogenesis are not fully resolved. Gut microbiota and its metabolites play a crucial role in maintaining energy homeostasis. Here, we investigated whether the aqueous extracts of Aconite (AA) can enhance thermogenesis through modulation of the composition and metabolism of gut microbiota in hypothermic rats. Methods: The therapeutic effects of AA on body temperature, energy intake, and the histopathology of white adipose tissue and brown adipose tissue of hypothermic rats were assessed. Microbiota analysis based on 16 S rRNA and targeted metabolomics for bile acids (BAs) were used to evaluate the composition of gut microbiota and BAs pool. The antibiotic cocktail treatment was adopted to further confirm the relationship between the gut microbiota and the thermogenesis-promoting effects of AA. Results: Our results showed a sharp drop in rectal temperature and body surface temperature in hypothermic rats. Administration of AA can significantly increase core body temperature, surface body temperature, energy intake, browning of white adipose tissue, and thermogenesis of brown adipose tissue. Importantly, these ameliorative effects of AA were accompanied by the shift of the disturbed composition of gut microbiota toward a healthier profile and the increased levels of BAs. In addition, the depletion of gut microbiota and the reduction of BAs caused by antibiotic cocktails reduced the thermogenesis-promoting effect of AA. Conclusions: Our results demonstrated that AA promoted thermogenesis in rats with hypothermia via regulating gut microbiota and BAs metabolism. Our findings can also provide a novel solution for the treatment of thermogenesis-associated diseases such as rheumatoid arthritis, obesity, and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: The relationship between betatrophin/ANGPTL8 and obesity has been investigated using body mass index (BMI); however, since BMI reflects overall adiposity rather than body fat distribution, it remains unclear whether fat deposition in different areas of the body affects betatrophin expression. Here, we investigated the correlation between circulating betatrophin levels and body fat distribution in patients with different glucose tolerance. Methods: We performed a cross-sectional study in 128 participants with impaired glucose tolerance (IGT; n = 64) or normal glucose tolerance (NGT; n = 64). Circulating betatrophin levels were detected by enzyme-linked immunosorbent assay (ELISA). Body fat distribution (subcutaneous, visceral, and limb fat) was measured by magnetic resonance imaging (MRI) and a body fat meter. Results: After controlling for age, sex, and BMI, betatrophin was correlated positively with visceral adipose tissue-to-subcutaneous adipose tissue ratio (VAT/SAT ratio; r = 0.339, p = 0.009) and negatively with body fat ratio (BFR; r = − 0.275, p = 0.035), left lower limb fat ratio (LLR; r = − 0.330, p = 0.011), and right lower limb fat ratio (RLR; r = − 0.288, p = 0.027) in the NGT group, with these correlations remaining after controlling for triglycerides. VAT/SAT ratio (standardized β = 0.419, p = 0.001) was independently associated with serum betatrophin levels; however, betatrophin was not associated with body fat distribution variables in the IGT group. Conclusions: Circulating betatrophin levels correlated positively with VAT/SAT ratio and negatively with lower limb fat, but not with subcutaneous or upper limb fat, in individuals with normal glucose tolerance. Thus, betatrophin may be a potential biomarker for body fat distribution in individuals without glucose disorders. [ABSTRACT FROM AUTHOR]

Background: In the field of drug repositioning, it is assumed that similar drugs may treat similar diseases, therefore many existing computational methods need to compute the similarities of drugs and diseases. However, the calculation of similarity depends on the adopted measure and the available features, which may lead that the similarity scores vary dramatically from one to another, and it will not work when facing the incomplete data. Besides, supervised learning based methods usually need both positive and negative samples to train the prediction models, whereas in drug-disease pairs data there are only some verified interactions (positive samples) and a lot of unlabeled pairs. To train the models, many methods simply treat the unlabeled samples as negative ones, which may introduce artificial noises. Herein, we propose a method to predict drug-disease associations without the need of similarity information, and select more likely negative samples. Results: In the proposed EMP-SVD (Ensemble Meta Paths and Singular Value Decomposition), we introduce five meta paths corresponding to different kinds of interaction data, and for each meta path we generate a commuting matrix. Every matrix is factorized into two low rank matrices by SVD which are used for the latent features of drugs and diseases respectively. The features are combined to represent drug-disease pairs. We build a base classifier via Random Forest for each meta path and five base classifiers are combined as the final ensemble classifier. In order to train out a more reliable prediction model, we select more likely negative ones from unlabeled samples under the assumption that non-associated drug and disease pair have no common interacted proteins. The experiments have shown that the proposed EMP-SVD method outperforms several state-of-the-art approaches. Case studies by literature investigation have found that the proposed EMP-SVD can mine out many drug-disease associations, which implies the practicality of EMP-SVD. Conclusions: The proposed EMP-SVD can integrate the interaction data among drugs, proteins and diseases, and predict the drug-disease associations without the need of similarity information. At the same time, the strategy of selecting more reliable negative samples will benefit the prediction. [ABSTRACT FROM AUTHOR]

Background: Papain-like cysteine proteases (PLCPs), a large group of cysteine proteases structurally related to papain, play important roles in plant development, senescence, and defense responses. Papain, the first cysteine protease whose structure was determined by X-ray crystallography, plays a crucial role in protecting papaya from herbivorous insects. Except the four major PLCPs purified and characterized in papaya latex, the rest of the PLCPs in papaya genome are largely unknown. Results: We identified 33 PLCP genes in papaya genome. Phylogenetic analysis clearly separated plant PLCP genes into nine subfamilies. PLCP genes are not equally distributed among the nine subfamilies and the number of PLCPs in each subfamily does not increase or decrease proportionally among the seven selected plant species. Papaya showed clear lineage-specific gene expansion in the subfamily III. Interestingly, all four major PLCPs purified from papaya latex, including papain, chymopapain, glycyl endopeptidase and caricain, were grouped into the lineagespecific expansion branch in the subfamily III. Mapping PLCP genes on chromosomes of five plant species revealed that lineage-specific expansions of PLCP genes were mostly derived from tandem duplications. We estimated divergence time of papaya PLCP genes of subfamily III. The major duplication events leading to lineage-specific expansion of papaya PLCP genes in subfamily III were estimated at 48 MYA, 34 MYA, and 16 MYA. The gene expression patterns of the papaya PLCP genes in different tissues were assessed by transcriptome sequencing and qRT-PCR. Most of the papaya PLCP genes of subfamily III expressed at high levels in leaf and green fruit tissues. Conclusions: Tandem duplications played the dominant role in affecting copy number of PLCPs in plants. Significant variations in size of the PLCP subfamilies among species may reflect genetic adaptation of plant species to different environments. The lineage-specific expansion of papaya PLCPs of subfamily III might have been promoted by the continuous reciprocal selective effects of herbivore attack and plant defense. [ABSTRACT FROM AUTHOR]

Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease with high penetrance caused by a germline variant of TP53 gene. We report the first case of endometrial cancer after yolk sac tumor with LFS. Case presentation: The presented female patient underwent right adnexectomy at age 23 because of a yolk sac tumor of the ovary. At the age of 27, the patient was diagnosed with endometrial adenocarcinoma, received cytoreductive surgery and chemotherapy. Given that her personal cancer history along with a strong family history of cancer, her father passing away from lung cancer at age 48 and her grandmother dying of ovarian cancer at age 50, the patient was referred for genetic counseling and testing. Genetic screening revealed a heterozygous pathogenic TP53 c.844C > T, p.(R282 W) with NM_000546.5 variant, a class 5 (C5) variant. This is the first reported case of a yolk sac tumor accompanied by subsequent endometrial cancer that is associated with LFS. Conclusions: We reported a first case of an endometrial cancer after yolk sac tumor patient with a tumor family history of harboring the germline TP53 pathogenic variation which expanded types of tumor that can be presented in patients with LFS. This case highlights the importance of genetic testing for patients with malignant tumors, as well as patients with a family history of malignant tumors. And our case highlights the necessity of screening for gynecologic tumor in LFS patients. [ABSTRACT FROM AUTHOR]

Objectives: In 2014, Ontario's Point-of-Care (POC) test providers were advised to focus efforts on provincially defined priority populations who experience a greater risk of HIV. Our objective was to describe the POC program before, during and after this change, including tester characteristics, follow-up testing results, positive predictive value (PPV) over time, and trends and characteristics of those with reactive test results without a confirmatory serological specimen. Methods: Test-level data of POC screening and confirmatory results were extracted from the Public Health Ontario HIV Datamart. Final test results were defined based on results of the confirmatory blood sample, or the POC test for "non-reactive" tests. Testing volumes, percent of total tests, percent positivity and PPV were calculated overall, annually, and by exposure group. Results: Overall testing volumes decreased by 39.8% between 2014 and 2018. The majority of confirmed positive tests were in the men who have sex with men (MSM) exposure category, followed by HIV-endemic and heterosexual – no identified risk (heterosexual—NIR). Overall percent positivity decreased from 0.59% in 2011 to 0.42% in 2015 (change of 0.17%, 95% CI 0.03% to 0.31%), increasing to 0.69% in 2018 (change of 0.27%, 95% CI 0.20% to 0.34%). Increases in percent positivity corresponded with a decrease in the overall proportion of tests conducted in low-risk populations. When compared to the heterosexual-NIR category, PPV was significantly higher for men who have sex with men – people who use injection drugs (MSM-PWID) (52.7% compared to 100%, P <.001), MSM (52.7% compared to 95.4%, P <.001), HIV-endemic (52.7% compared to 91.5%, P <.001), heterosexual – partner with identified risk (heterosexual—PIR) (52.7% compared to 77.3%, P =.042), and people who use injection drugs (PWID) (52.7% compared to 81.3%, P = 0.007). A total of 13.5% of reactive POC results did not have a serological sample submitted. Conclusions: Targeted testing towards populations at higher risk of HIV improved the overall test performance characteristics of Ontario's POC testing program. While not unexpected, the large discrepancies between PPV in higher-risk, compared to lower-risk populations, suggests the need for greater awareness and messaging of the likelihood of false positive test results in different populations. [ABSTRACT FROM AUTHOR]

Background: Aberrant inflammatory responses drive the initiation and progression of various diseases, and hyperactivation of NLRP3 inflammasome is a key pathogenetic mechanism. Pharmacological inhibitors of NLRP3 represent a potential therapy for treating these diseases but are not yet clinically available. The natural product butein has excellent anti-inflammatory activity, but its potential mechanisms remain to be investigated. In this study, we aimed to evaluate the ability of butein to block NLRP3 inflammasome activation and the ameliorative effects of butein on NLRP3-driven diseases. Methods: Lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages were pretreated with butein and various inflammasome stimuli. Intracellular potassium levels, ASC oligomerization and reactive oxygen species production were also detected to evaluate the regulatory mechanisms of butein. Moreover, mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis were used to test whether butein has protective effects on these NLRP3-driven diseases. Results: Butein blocks NLRP3 inflammasome activation in mouse macrophages by inhibiting ASC oligomerization, suppressing reactive oxygen species production, and upregulating the expression of the antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Importantly, in vivo experiments demonstrated that butein administration has a significant protective effect on the mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis. Conclusion: Our study illustrates the connotation of homotherapy for heteropathy, i.e., the application of butein to broaden therapeutic approaches and treat multiple inflammatory diseases driven by NLRP3. [ABSTRACT FROM AUTHOR]

Gliomas are the most common primary intracranial tumor worldwide. The maintenance of telomeres serves as an important biomarker of some subtypes of glioma. In order to investigate the biological role of RTEL1 in glioma. Relative telomere length (RTL) and RTEL1 mRNA was explored and regression analysis was performed to further examine the relationship of the RTL and the expression of RTEL1 with clinicopathological characteristics of glioma patients. We observed that high expression of RTEL1 is positively correlated with telomere length in glioma tissue, and serve as a poor prognostic factor in TERT wild-type patients. Further in vitro studies demonstrate that RTEL1 promoted proliferation, formation, migration and invasion ability of glioma cells. In addition, in vivo studies also revealed the oncogene role of RTEL1 in glioma. Further study using RNA sequence and phospho-specific antibody microarray assays identified JNK/ELK1 signaling was up-regulated by RTEL1 in glioma cells through ROS. In conclusion, our results suggested that RTEL1 promotes glioma tumorigenesis through JNK/ELK1 cascade and indicate that RTEL1 may be a prognostic biomarker in gliomas. [ABSTRACT FROM AUTHOR]

Objective: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies. Methods: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs). Results: Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein–protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages. Conclusion: Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation. [ABSTRACT FROM AUTHOR]

Background: The pistil is an essential part of flowers that functions in the differentiation of the sexes and reproduction in plants. The stigma on the pistil can accept pollen to allow fertilization and seed development. Papaya (Carica papaya L.) is a dioecious plant, where female flowers exhibit normal pistil, while the male flowers exhibit aborted pistil at a late stage of pistil development. Results: The developmental stages of papaya pistil were analyzed after first dividing it into slices representing the primordium stage 1 (S1), the pre-meiotic stages S2, post-meiotic stage S3, and the mitotic stage S4. The SS scoring algorithm analysis of genes preferentially expressed at different stages revealed differentially expressed genes between male and female flowers. A transcription factor regulatory network for each stage based on the genes that are differentially expressed between male and female flowers was constructed. Some transcription factors related to pistil development were revealed based on the analysis of regulatory networks such as CpAGL11, CpHEC2, and CpSUPL. Based on the specific expression of genes, constructed a gene regulatory subnetwork with CpAGL11-CpSUPL-CpHEC2 functioning as the core. Analysis of the functionally enriched terms in this network reveals several differentially expressed genes related to auxin/ brassinosteroid signal transduction in the plant hormone signal transduction pathway. At the same time, significant differences in the expression of auxin and brassinosteroid synthesis-related genes between male and female flowers at different developmental stages were detected. Conclusions: The pistil abortion of papaya might be caused by the lack of expression or decreased expression of some transcription factors and hormone-related genes, affecting hormone signal transduction or hormone biosynthesis. Analysis of aborted and normally developing pistil in papaya provided new insights into the molecular mechanism of pistil development and sex differentiation in dioecious papaya. [ABSTRACT FROM AUTHOR]

Background: Since genes involved in the same biological modules usually present correlated expression profiles, lots of computational methods have been proposed to identify gene functional modules based on the expression profiles data. Recently, Sparse Singular Value Decomposition (SSVD) method has been proposed to bicluster gene expression data to identify gene modules. However, this model can only handle the gene expression data where no gene interaction information is integrated. Ignoring the prior gene interaction information may produce the identified gene modules hard to be biologically interpreted. Results: In this paper, we develop a Sparse Network-regularized SVD (SNSVD) method that integrates a prior gene interaction network from a protein protein interaction network and gene expression data to identify underlying gene functional modules. The results on a set of simulated data show that SNSVD is more effective than the traditional SVD-based methods. The further experiment results on real cancer genomic data show that most co-expressed modules are not only significantly enriched on GO/KEGG pathways, but also correspond to dense sub-networks in the prior gene interaction network. Besides, we also use our method to identify ten differentially co-expressed miRNA-gene modules by integrating matched miRNA and mRNA expression data of breast cancer from The Cancer Genome Atlas (TCGA). Several important breast cancer related miRNA-gene modules are discovered. Conclusions: All the results demonstrate that SNSVD can overcome the drawbacks of SSVD and capture more biologically relevant functional modules by incorporating a prior gene interaction network. These identified functional modules may provide a new perspective to understand the diagnostics, occurrence and progression of cancer. [ABSTRACT FROM AUTHOR]

Background: Rabies virus (RABV) is reported to encode five phosphoproteins (P), which are involved in viral genomic replication, axonal transport, oxidative stress, interferon antagonism, and autophagy induction. However, the functions of the different P proteins are poorly understood. Methods: Immunofluorescence staining and western blot were performed to detect the autophagy activity, the form of ring-like structure, and the colocalization of BECN1 and P. Co-immunoprecipitation was performed to detect the interaction between P and BECN1. QRT-PCR and TCID50 assay were performed to detect the replication level of RABV. Small interfering RNA was used to detect the autophagy signaling pathway. Results: We found that P5 attaches to N-terminal residues 1–139 of BECN1 (beclin1) on the BECN1 ring-like structure through amino acid residues 173–222 of P5. Subsequently, we found that P5-induced autophagosomes did not fuse with lysosomes. Becn1 silencing did not recover P5 overexpression-induced promotion of RABV replication. Mechanistically, RABV protein PΔN82 (P5) induced incomplete autophagy via the BECN1-mediated signaling pathway. Conclusions: Our data indicate that P5 binding to the BECN1 ring benefits RABV replication by inducing BECN1 signaling pathway-dependent incomplete autophagy, which provides a potential target for antiviral drugs against RABV. 1BoHPEPoc4wqHnwcyFSWMb Video abstract [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy in women. Cancer driver gene-mediated alterations in the tumor microenvironment are critical factors affecting the biological behavior of breast cancer. The purpose of this study was to identify the expression characteristics and prognostic value of cancer driver genes in breast cancer. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets are used as the training and test sets. Classified according to cancer and paracancerous tissues, we identified differentially expressed cancer driver genes. We further screened prognosis-associated genes, and candidate genes were submitted for the construction of a risk signature. Functional enrichment analysis and transcriptional regulatory networks were performed to search for possible mechanisms by which cancer driver genes affect breast cancer prognosis. Results: We identified more than 200 differentially expressed driver genes and 27 prognosis-related genes. High-risk group patients had a lower survival rate compared to the low-risk group (P<0.05), and risk signature showed high specificity and sensitivity in predicting the patient prognosis (AUC 0.790). Multivariate regression analysis suggested that risk scores can independently predict patient prognosis. Further, we found differences in PD-1 expression, immune score, and stromal score among different risk groups. Conclusion: Our study confirms the critical prognosis role of cancer driver genes in breast cancer. The cancer driver gene risk signature may provide a novel biomarker for clinical treatment strategy and survival prediction of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that HBV pregenome RNA (HBV pgRNA) could predict HBeAg seroconversion among the chronic hapatitis B (CHB) patients treated with pegylated interferon (Peg-IFN) or nucleos(t)ide analogues (NAs). However, the data about the prediction of HBV pgRNA for spontaneous HBeAg seroconversion is limited. Methods: One hundred thirteen CHB patients with HBeAg-positive in the immune active phase were followed up for 76 weeks without antiviral treatment. Based on the laboratory test results of liver function, HBeAg, anti-HBe, and HBV DNA at week 76, patients were assigned to two groups: spontaneous HBeAg seroconversion (group A, n = 18) and non-spontaneous HBeAg seroconversion group. Among the latter group, 36 patients were selected as controls (group B, n = 36). Results: At week 12, between group A and group B, there was a significant difference in the level of HBV pgRNA (group A 6.35 ± 1.24 log10 copies/ml and group B 7.52 ± 0.79 log10 copies/ml, P = 0.001), and the difference enlarged at week 28. The receiver operating characteristic curves (AUROCs) of the HBV pgRNA level and the ∆HBV pgRNA at week 28 were 0.912 (P = 0.001, 95% CI: 0.830–0.994), and 0.934 (P = 0.001, 95% CI: 0.872–0.996), respectively. The optimal cutoffs of HBV pgRNA and the reduction from baseline (∆HBV pgRNA) at week 28 for spontaneous HBeAg seroconversion prediction were 5.63 log10 copies/ml and 1.85 log10 copies/ml, respectively. The positive predictive value and negative predictive value of HBV pgRNA and ∆HBV pgRNA at week 28 were 86.7% and 87.2%, 87.5% and 89.5%, respectively. And the combination of the HBV pgRNA level and the HBV pgRNA decreased could provide better prediction. Conclusions: HBV pgRNA is a sound predictor for spontaneous HBeAg seroconversion among the CHB patients in immune active phase. Dynamic monitoring of HBV pgRNA is helpful for clinical treatment decision. [ABSTRACT FROM AUTHOR]

Background: Hand, foot, and mouth disease (HFMD) is a viral disease caused by human enteroviruses. Although HFMD reinfection is common, studies investigating this phenomenon are insufficient.Methods: The present study focused on HFMD reinfection in Wuxi from 2008 to 2016 using surveillance system data.Results: Of 107,677 cases included in the study, 6470 cases were classified as reinfections. The overall reinfection rate was 6.01% (6.37% male and 5.48% female patients), which decreased with increasing age (χ2 = 1125.477, p < 0.001). The rate was 6.17 and 5.79% in urban and rural areas, respectively, and 7.83 and 5.98% of the cases were severe and mild, respectively. Multivariate logistic regression analysis showed that male sex, younger age, residence in an urban area, and severe disease were risk factors for HFMD reinfection. The case-severity rate in secondary infection cases was lower than that in non-reinfection cases (odds ratio 0.675, 95% confidence interval 0.526-0.866).Conclusions: Boys younger than 4 years of age living in urban areas were more prone to reinfection. Specific health education and intervention should be developed to protect these susceptible populations. [ABSTRACT FROM AUTHOR]

Background: Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms. Methods: Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity. Results: Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX. Conclusion: Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa. [ABSTRACT FROM AUTHOR]

Background: Previous in vitro studies demonstrated that suppression of microRNAs might protect cardiomyocytes and neurons against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell apoptosis. However, whether the protective effect of miR-153-inhibition on cardiomyocytes can be observed in the animal model is unknown. We aimed to address this question using a rat model of ischemia-reperfusion (I/R).Methods: Rats were received the intramyocardial injection of saline or adenovirus-carrying target or control gene, and the rats were subjected to ischemia/reperfusion (I/R) treatment. The effects of miR-153 on I/R-induced inflammatory response and oxidative stress in the rat model were assessed using various assays.Results: We found that suppression of miR-153 decreased cleaved caspase-3 and Bcl-2-associated X (Bax) expression, and increased B cell lymphoma 2 (Bcl-2) expression. We further confirmed that Nuclear transcription factor erythroid 2-like 2 (Nrf2) is a functional target of miR-153, and Nrf2/Heme oxygenase-1 (HO-1) signaling was involved in miR-153-regulated I/R-induced cardiomyocytes apoptosis. Inhibition of miR-153 reduced I/R-induced inflammatory response and oxidative stress in rat myocardium.Conclusion: Suppression of miR-153 exerts a cardioprotective effect against I/R-induced injury through the regulation of Nrf2/HO-1 signaling, suggesting that targeting miR-153, Nrf2, or both may serve as promising therapeutic targets for the alleviation of I/R-induced injury. [ABSTRACT FROM AUTHOR]

Background: Migratory birds play an important part in the spread of parasites, with more or less impact on resident birds. Previous studies focus on the prevalence of parasites, but changes in infection intensity over time have rarely been studied. As infection intensity can be quantified by qPCR, we measured infection intensity during different seasons, which is important for our understanding of parasite transmission mechanisms. Methods: Wild birds were captured at the Thousand Island Lake with mist nets and tested for avian hemosporidiosis infections using nested PCR. Parasites were identified using the MalAvi database. Then, we used qPCR to quantify the infection intensity. We analyzed the monthly trends of intensity for all species and for different migratory status, parasite genera and sexes. Results: Of 1101 individuals, 407 were infected (37.0%) of which 95 were newly identified and mainly from the genus Leucocytozoon. The total intensity trend shows peaks at the start of summer, during the breeding season of hosts and during the over-winter season. Different parasite genera show different monthly trends. Plasmodium causes high prevalence and infection intensity of winter visitors. Female hosts show significant seasonal trends of infection intensity. Conclusions: The seasonal changes of infection intensity is consistent with the prevalence. Peaks occur early and during the breeding season and then there is a downward trend. Spring relapses and avian immunity are possible reasons that could explain this phenomenon. In our study, winter visitors have a higher prevalence and infection intensity, but they rarely share parasites with resident birds. This shows that they were infected with Plasmodium during their departure or migration and rarely transmit the disease to resident birds. The different infection patterns of different parasite species may be due to vectors or other ecological properties. [ABSTRACT FROM AUTHOR]

Background: Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation. Methods: This multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred. Results: Overall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P < 0.001) and EOT hepatitis B core-related antigen (HBcrAg) (HR = 0.257, P = 0.001) were associated with HBsAg loss. The areas under the receiver operating characteristic curves for EOT HBsAg and HBcrAg levels were 0.952 (P < 0.001) and 0.765 (P < 0.001), respectively. Patients with EOT HBsAg ≤ 135 IU/mL (59.2% vs. 1.3%, P < 0.001) or HBcrAg ≤ 3.6 logU/mL (17% vs. 5.4%, P = 0.027) had a higher 24-month cumulative HBsAg loss rate. In Group B, none of the patients experienced virological relapse after NA cessation. Only 1 (5.3%) patient had HBsAg reversion. Conclusions: EOT HBsAg ≤ 135 IU/mL or HBcrAg ≤ 3.6 logU/mL can be used to identify patients with a higher likelihood of HBsAg loss after NA cessation. Patients with HBsAg negativity after NA cessation have favorable clinical outcomes, and HBsAg loss was durable in most cases. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMF) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear. Methods: NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF. Results: Exposure to EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. The EMF boosted CaMKKβ protein expression, activated AMPK phosphorylation and suppressed mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by PEMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage caused by oxidative stress in HFD-fed mice. Conclusions: EMF may activate the CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD. [ABSTRACT FROM AUTHOR]

Background: The interaction between tumor cells and immune or non-immune stromal cells creates a unique tumor microenvironment, which plays an important role in the growth, invasion and metastasis of gastric cancer (GC). Methods: The candidate genes were selected to construct risk-score by univariate and multivariate Cox regression analysis. Nomograms were constructed by combining clinical pathological factors, and the model performance was evaluated by receiver operating characteristic curve, decision curve analysis, net reclassification improvement and integrated discrimination improvement. The functional enrichment between high-risk group (HRisk) and low-risk group (LRisk) was explored through GO, KEGG, GSVA and ssGSEA. CIBERSORT, quanTIseq and xCell were used to explore the immune cell infiltration between HRisk and LRisk. The relevant EMT scores, macrophage infiltration scores and various metabolic scores were calculated through the "IOBR" package and analyzed visually. Results: Through univariate and multivariate Cox regression analysis, we obtained the risk-score of fittings six lipid metabolism related genes (LMAGs). Through survival analysis, we found that risk-score has significant prognostic significance and can accurately reflect the metabolic level of patients. The AUCs of the nomogram model incorporating risk-score 1, 3 and 5 years were 0.725, 0.729 and 0.749 respectively. In addition, it was found that the inclusion of risk-score could significantly improve the prediction performance of the model. It was found that the arachidonic acid metabolism and prostaglandin synthesis were up-regulated in HRisk, and more tumor metastasis related markers and immune related pathways were also enriched. Further study found that HRisk had higher immune score and M2 macrophage infiltration. More importantly, the immune checkpoints of tumor associated macrophages involved in tumor antigen recognition disorders increased significantly. We also found that ST6GALNAC3 can promote arachidonic acid metabolism and up-regulate prostaglandin synthesis, increase M2 macrophage infiltration, induce epithelial mesenchymal transformation, and affect the prognosis of patients. Conclusions: Our research found a novel and powerful LMAGs signature. Six-LMAGs features can effectively evaluate the prognosis of GC patients and reflect the metabolic and immune status. ST6GALNAC3 may be a potential prognostic marker to improve the survival rate and prognostic accuracy of GC patients, and may even be a potential biomarker of GC patients, indicating the response to immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial peptides (AMPs) are essential components of the innate immune system and can protect the host from various pathogenic bacteria. The marine environment is known to be one of the richest sources for AMPs. Effective usage of AMPs and their derivatives can greatly improve the immunity and breeding survival rate of aquatic products. It is highly desirable to develop computational tools for rapidly and accurately identifying AMPs and their functional types, for the purpose of helping design new and more effective antimicrobial agents. Results: In this study, we made an attempt to develop an advanced machine learning based computational approach, MAMPs-Pred, for identification of AMPs and its function types. Initially, SVM-prot 188-D features were extracted that were subsequently used as input to a two-layer multi-label classifier. In specific, the first layer is to identify whether it is an AMP by applying RF classifier, and the second layer addresses the multi-type problem by identifying the activites or function types of AMPs by applying PS-RF and LC-RF classifiers. To benchmark the methods,the MAMPs-Pred method is also compared with existing best-performing methods in literature and has shown an improved identification accuracy. Conclusions: The results reported in this study indicate that the MAMP-Pred method achieves high performance for identifying AMPs and its functional types.The proposed approach is believed to supplement the tools and techniques that have been developed in the past for predicting AMPs and their function types. [ABSTRACT FROM AUTHOR]

Background: Aligning protein-protein interaction (PPI) networks is very important to discover the functionally conserved sub-structures between different species. In recent years, the global PPI network alignment problem has been extensively studied aiming at finding the one-to-one alignment with the maximum matching score. However, finding large conserved components remains challenging due to its NP-hardness. Results: We propose a new graph matching method GMAlign for global PPI network alignment. It first selects some pairs of important proteins as seeds, followed by a gradual expansion to obtain an initial matching, and then it refines the current result to obtain an optimal alignment result iteratively based on the vertex cover. We compare GMAlign with the state-of-the-art methods on the PPI network pairs obtained from the largest BioGRID dataset and validate its performance. The results show that our algorithm can produce larger size of alignment, and can find bigger and denser common connected subgraphs as well for the first time. Meanwhile, GMAlign can achieve high quality biological results, as measured by functional consistency and semantic similarity of the Gene Ontology terms. Moreover, we also show that GMAlign can achieve better results which are structurally and biologically meaningful in the detection of large conserved biological pathways between species. Conclusions: GMAlign is a novel global network alignment tool to discover large conserved functional components between PPI networks. It also has many potential biological applications such as conserved pathway and protein complex discovery across species. The GMAlign software and datasets are avaialbile at https://github.com/yzlwhu/GMAlign. [ABSTRACT FROM AUTHOR]

Background: Trigger thumb is a pathologic condition of the digital pulleys and flexor tendons. To find a cutoff value of the cross-sectional area ratio of specific parts of the flexor pollicis longus tendon to diagnosis trigger thumb in the high-frequency ultrasound examination. Methods: We evaluated 271 healthy volunteers and 57 patients with clinical diagnosis of trigger thumb. The cross-sectional area of the metacarpophalangeal joint of flexor pollicis longus tendon (C1) and the cross-sectional area of the midpoint of the first metacarpal of flexor pollicis longus tendon (C2) were analyzed. Results: There is no difference between gender, age and left and right hands in the ratio of C1 to C2 (C1/ C2). The mean of C1/ C2 in the healthy thumb was 0.983 ± 0.103, which was significantly smaller in comparison to the diseased thumb (P < 0.05). Based on the receiver operating characteristic curve, we chose the diagnostic cut-off value for the C1/ C2 to be 1.362 and 1.153 in order to differ a trigger thumb from children and adults. Conclusions: The C1/ C2 of the healthy thumb was relatively stable, with a mean value of 0.983 ± 0.103. The cutoff value of C1/C2 to distinguish healthy thumb from diseased thumb in children and adults were 1.362 and 1.153, respectively. [ABSTRACT FROM AUTHOR]

Straw biorefinery offers economical and sustainable production of chemicals. The merits of cell immobilization technology have become the key technology to meet d-lactic acid production from non- detoxified corn stover. In this paper, Low acyl gellan gum (LA-GAGR) was employed first time for Lactobacillus bulgaricus T15 immobilization and applied in d-lactic acid (D-LA) production from non-detoxified corn stover hydrolysate. Compared with the conventional calcium alginate (E404), LA-GAGR has a hencky stress of 82.09 kPa and excellent tolerance to 5-hydroxymethylfurfural (5-HMF), ferulic acid (FA), and vanillin. These features make LA-GAGR immobilized T15 work for 50 days via cell-recycle fermentation with D-LA yield of 2.77 ± 0.27 g/L h, while E404 immobilized T15 can only work for 30 days. The production of D-LA from non-detoxified corn stover hydrolysate with LA-GAGR immobilized T15 was also higher than that of free T15 fermentation and E404 immobilized T15 fermentation. In conclusion, LA-GAGR is an excellent cell immobilization material with great potential for industrial application in straw biorefinery industry. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SZ) arises from a complex interplay involving genetic and molecular factors. Early intervention of SZ hinges upon understanding its vulnerability and resiliency factors in study of SZ and genetic high risk for SZ (GHR). Methods: Herein, using integrative and multimodal strategies, we first performed a longitudinal study of neural function as measured by amplitude of low frequency function (ALFF) in 21 SZ, 26 GHR, and 39 healthy controls to characterize neurodevelopmental trajectories of SZ and GHR. Then, we examined the relationship between polygenic risk score for SZ (SZ-PRS), lipid metabolism, and ALFF in 78 SZ, and 75 GHR in cross-sectional design to understand its genetic and molecular substrates. Results: Across time, SZ and GHR diverge in ALFF alterations of the left medial orbital frontal cortex (MOF). At baseline, both SZ and GHR had increased left MOF ALFF compared to HC (P < 0.05). At follow-up, increased ALFF persisted in SZ, yet normalized in GHR. Further, membrane genes and lipid species for cell membranes predicted left MOF ALFF in SZ; whereas in GHR, fatty acids best predicted and were negatively correlated (r = -0.302, P < 0.05) with left MOF. Conclusions: Our findings implicate divergence in ALFF alteration in left MOF between SZ and GHR with disease progression, reflecting vulnerability and resiliency to SZ. They also indicate different influences of membrane genes and lipid metabolism on left MOF ALFF in SZ and GHR, which have important implications for understanding mechanisms underlying vulnerability and resiliency in SZ and contribute to translational efforts for early intervention. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignancy with poor patient prognosis. Current treatment for ESCC, including immunotherapy, is only beneficial for a small subset of patients. Better characterization of the tumor microenvironment (TME) and the development of novel therapeutic targets are urgently needed. Methods: In the present study, we hypothesized that integration of single-cell transcriptomic sequencing and large microarray sequencing of ESCC biopsies would reveal the key cell subtypes and therapeutic targets that determine the prognostic and tumorigenesis of ESCC. We characterized the gene expression profiles, gene sets enrichment, and the TME landscape of a microarray cohort including 84 ESCC tumors and their paired peritumor samples. We integrated single-cell transcriptomic sequencing and bulk microarray sequencing of ESCC to reveal key cell subtypes and druggable targets that determine the prognostic and tumorigenesis of ESCC. We then designed and screened a blocking peptide targeting Chemokine C–C motif ligand 18 (CCL18) derived from tumor associated macrophages and validated its potency by MTT assay. The antitumor activity of CCL18 blocking peptide was validated in vivo by using 4-nitroquinoline-1-oxide (4-NQO) induced spontaneous ESCC mouse model. Results: Comparative gene expression and cell–cell interaction analyses revealed dysregulated chemokine and cytokine pathways during ESCC carcinogenesis. TME deconvolution and cell interaction analyses allow us to identify the chemokine CCL18 secreted by tumor associated macrophages could promote tumor cell proliferation via JAK2/STAT3 signaling pathway and lead to poor prognosis of ESCC. The peptide Pep3 could inhibit the proliferation of EC-109 cells promoted by CCL18 and significantly restrain the tumor progression in 4-NQO-induced spontaneous ESCC mouse model. Conclusions: For the first time, we discovered and validated that CCL18 blockade could significantly prevent ESCC progression. Our study revealed the comprehensive cell–cell interaction network in the TME of ESCC and provided novel therapeutic targets and strategies to ESCC treatment. [ABSTRACT FROM AUTHOR]

Background: Female sex workers (FSWs) are at risk for sexually transmitted infections (STIs), including HIV. We implemented an HIV/STI preventive intervention among FSWs in Shanghai that aimed to increase condom use, improve HIV knowledge, and reduce STI and HIV incidence.Methods: From six districts in Shanghai, 750 randomly selected venue-based FSWs were allocated to either a behavioural intervention or control group. In the intervention and control groups, 221 and 278 participants, respectively, had at least one follow-up at three or six months. In analysis, we randomly selected 57 lost to follow-up cases in the intervention group and imputed baseline values to equalize the arms at n = 278 (74.1% follow-up rate in each group). The impacts of the intervention on condom use, HIV/STI risk perception and knowledge, and STI incidence were assessed using either a logistic or linear model, adjusting for the baseline measure of the outcome and venue type.Results: The intervention improved consistent condom use with any partner type in the previous month (AOR = 2.09, 95% CI, 1.43-3.04, p = 0.0001). Consistent condom use with clients in the three most recent sex acts increased in both arms, and with primary partners in the intervention arm, but there was no difference between groups after adjusting for baseline condom use and venue type. There were no differences in cumulative incidence of any STI (i.e., chlamydia, gonorrhoea, syphilis) between groups. HIV transmission knowledge (p = 0.0001), condom use skill (p = 0.0421), and self-efficacy for using condoms (p = 0.0071) were improved by the intervention. HIV-related stigma declined (p = 0.0119) and HIV and STI risk perception were improved (4.6 to 13.9%, and 9.4 to 20.0%, respectively). The intervention was associated with these improvements after adjusting for the baseline measure and venue type.Conclusion: Following a preventive intervention among Shanghai FSWs, our findings demonstrate that a simple, community-based educational intervention improved overall condom use, HIV and STI knowledge, and attitudes in relation to HIV/AIDS. The intervention should be implemented widely after tailoring educational materials regarding condom negotiation with different partner types (i.e., commercial sex clients and primary partners). [ABSTRACT FROM AUTHOR]

Background: Fear of childbirth (FOC) is a common psychological problem in Chinese pregnant women. FOC can influence both maternal health and infants' wellness. Special assessment tools for FOC in Mandarin Chinese are currently lacking. The aim of this study was to evaluate the psychometric properties of the Mandarin Chinese of the Wijma Delivery Expectancy/Experience Questionnaire Version A (W-DEQ-A). Methods: We recruited 364 Chinese pregnant women from April 2021 to July 2021. Translation and cultural adaptation, as well as reliability and validity testing were conducted. Analyses included the content validity, structural validity, criterion-related validity, convergent validity and reliability. The content validity indices were used to assess the content validity of the tool. The structural validity was tested through exploratory factor analysis and confirmatory factor analysis. The Cronbach's alpha coefficient was used to evaluate the reliability of the W-DEQ-A Chinese version. Results: The Chinese translation showed excellent similarities and equivalence to the original version, with the satisfactory content validity. Factor analysis indicated 5 factors, accounting for 57% of the total variance. Both criterion-related validity and convergent validity proved to be acceptable. The reliability was tested with a Cronbach's alpha coefficient of 0.911 for the total scale. Conclusion: The W-DEQ-A Chinese version is a reliable and valid tool to identify FOC in Mandarin Chinese-speaking populations. [ABSTRACT FROM AUTHOR]

Background: Time in range (TIR), a novel proxy measure of glucose control, is found closely related to diabetic microangiopathy and some other chronic complications, but the correlation between TIR and lower limb angiopathy has not been studied yet. Our purpose is to explore the relationship between TIR and abnormal ankle-brachial index(ABI) in type 2 diabetes. Methods: We retrospectively collected patients' information from the database and performed cross-sectional analysis. A total of 405 type 2 diabetes patients were enrolled in this study. ABI was measured and patients were stratified into low, normal, and high groups according to ≤ 0.9, > 0.9 and < 1.3, ≥ 1.3 ABI values. All patients underwent continuous glucose monitoring(CGM), and TIR was defined as the percentage of time in which glucose was in the range of 3.9–10 mmol/L during a 24-h period. Correlations between TIR and abnormal ABI were analyzed using Spearman analysis. And logistic regression was used to explore whether TIR is an independent risk factor for abnormal ABI. Results: The overall prevalence of abnormal ABI was 20.2% (low 4.9% and high 15.3%). TIR was lower in patients with abnormal ABI values (P = 0.009). The prevalence of abnormal ABI decreased with increasing quartiles of TIR (P = 0.026). Abnormal ABI was negatively correlated with TIR and positively correlated with hypertension, age, diabetes duration, UREA, Scr, ACR, TAR, MBG, and M values (P < 0.05). The logistic regression revealed a significant association between TIR and abnormal ABI, while HbA1C and blood glucose variability measures had no explicit correlation with abnormal ABI. Additionally, there was a significant difference in LDL between the low and high ABI groups (P = 0.009), and in Scr between normal and low groups (P = 0.007). And there were significant differences in TIR (P = 0.003), age (P = 0.023), UREA (P = 0.006), ACR (P = 0.004), TAR (P = 0.015), and MBG (P = 0.014) between normal and high ABI groups, and in diabetes duration between both normal and low (P = 0.023) and normal and high (P = 0.006) groups. Conclusions: In type 2 diabetes patients, abnormal ABI is associated with lower TIR, and the correlation is stronger than that with HbA1C. Therefore, the role of TIR should be emphasized in the evaluation of lower limb vascular diseases. [ABSTRACT FROM AUTHOR]

Background: Fear of childbirth (FOC) is a common psychological problem in Chinese pregnant women. FOC can influence both maternal health and infants' wellness. Special assessment tools for FOC in Mandarin Chinese are currently lacking. The aim of this study was to evaluate the psychometric properties of the Mandarin Chinese of the Wijma Delivery Expectancy/Experience Questionnaire Version A (W-DEQ-A). Methods: We recruited 364 Chinese pregnant women from April 2021 to July 2021. Translation and cultural adaptation, as well as reliability and validity testing were conducted. Analyses included the content validity, structural validity, criterion-related validity, convergent validity and reliability. The content validity indices were used to assess the content validity of the tool. The structural validity was tested through exploratory factor analysis and confirmatory factor analysis. The Cronbach's alpha coefficient was used to evaluate the reliability of the W-DEQ-A Chinese version. Results: The Chinese translation showed excellent similarities and equivalence to the original version, with the satisfactory content validity. Factor analysis indicated 5 factors, accounting for 57% of the total variance. Both criterion-related validity and convergent validity proved to be acceptable. The reliability was tested with a Cronbach's alpha coefficient of 0.911 for the total scale. Conclusion: The W-DEQ-A Chinese version is a reliable and valid tool to identify FOC in Mandarin Chinese-speaking populations. [ABSTRACT FROM AUTHOR]

Background: Infection with Trichomonas vaginalis can lead to cervicitis, urethritis, pelvic inflammatory disease, prostatitis and perinatal complications and increased risk of HIV transmission. Here, we used an RPA-based CRISPR-Cas12a assay system in combination with a lateral flow strip (LFS) (referred to as RPA-CRISPR-Cas12a) to establish a highly sensitive and field-ready assay and evaluated its ability to detect clinical samples. Methods: We developed a one-pot CRISPR-Cas12a combined with RPA-based field detection technology for T. vaginalis, chose actin as the target gene to design crRNA and designed RPA primers based on the crRNA binding site. The specificity of the method was demonstrated by detecting genomes from nine pathogens. To improve the usability and visualize the RPA-CRISPR-Cas12a assay results, both fluorescence detection and LFS readouts were devised. Results: The RPA-CRISPR-Cas12a assay platform was completed within 60 min and had a maximum detection limit of 1 copy/µl and no cross-reactivity with Candida albicans, Mycoplasma hominis, Neisseria gonorrhoeae, Escherichia coli, Cryptosporidium parvum, G. duodenalis or Toxoplasma gondii after specificity validation. Thirty human vaginal secretions were tested by RPA-CRISPR-Cas12a assays, and the results were read by a fluorescent reporter and LFS biosensors and then compared to the results from nested PCR detection of these samples. Both RPA-CRISPR-Cas12a assays showed 26.7% (8/30) T. vaginalis-positive samples and a consistency of 100% (8/8). The RPA-CRISPR-Cas12a assays had a higher sensitivity than nested PCR (only seven T. vaginalis-positive samples were detected). Conclusions: The T. vaginalis RPA-CRISPR-Cas12a assay platform in this study can be used for large-scale field testing and on-site tests without the need for trained technicians or costly ancillary equipment. [ABSTRACT FROM AUTHOR]

Background: Infection with Trichomonas vaginalis can lead to cervicitis, urethritis, pelvic inflammatory disease, prostatitis and perinatal complications and increased risk of HIV transmission. Here, we used an RPA-based CRISPR-Cas12a assay system in combination with a lateral flow strip (LFS) (referred to as RPA-CRISPR-Cas12a) to establish a highly sensitive and field-ready assay and evaluated its ability to detect clinical samples. Methods: We developed a one-pot CRISPR-Cas12a combined with RPA-based field detection technology for T. vaginalis, chose actin as the target gene to design crRNA and designed RPA primers based on the crRNA binding site. The specificity of the method was demonstrated by detecting genomes from nine pathogens. To improve the usability and visualize the RPA-CRISPR-Cas12a assay results, both fluorescence detection and LFS readouts were devised. Results: The RPA-CRISPR-Cas12a assay platform was completed within 60 min and had a maximum detection limit of 1 copy/µl and no cross-reactivity with Candida albicans, Mycoplasma hominis, Neisseria gonorrhoeae, Escherichia coli, Cryptosporidium parvum, G. duodenalis or Toxoplasma gondii after specificity validation. Thirty human vaginal secretions were tested by RPA-CRISPR-Cas12a assays, and the results were read by a fluorescent reporter and LFS biosensors and then compared to the results from nested PCR detection of these samples. Both RPA-CRISPR-Cas12a assays showed 26.7% (8/30) T. vaginalis-positive samples and a consistency of 100% (8/8). The RPA-CRISPR-Cas12a assays had a higher sensitivity than nested PCR (only seven T. vaginalis-positive samples were detected). Conclusions: The T. vaginalis RPA-CRISPR-Cas12a assay platform in this study can be used for large-scale field testing and on-site tests without the need for trained technicians or costly ancillary equipment. [ABSTRACT FROM AUTHOR]

Background: Although there are a lot of researches focusing on cancer prognosis or prediction of cancer metastases, it is still a big challenge to predict the risks of cancer metastasizing to a specific organ such as bone. In fact, little work has been published for such a purpose nowadays.Methods: In this work, we propose a Dysregulated Pathway Based prediction Model (DPBM) built on a merged data set with 855 samples. First, we use bootstrapping strategy to select bone metastasis related genes. Based on the selected genes, we then detect out the dysregulated pathways involved in the process of bone metastasis via enrichment analysis. And then we use the discriminative genes in each dysregulated pathway, called as dysregulated genes, to construct a sub-model to forecast the risk of bone metastasis. Finally we combine all sub-models as an ensemble model (DPBM) to predict the risk of bone metastasis.Results: We have validated DPBM on the training, test and independent sets separately, and the results show that DPBM can significantly distinguish the bone metastases risks of patients (with p-values of 3.82E-10, 0.00007 and 0.0003 on three sets respectively). Moreover, the dysregulated genes are generally with higher topological coefficients (degree and betweenness centrality) in the PPI network, which means that they may play critical roles in the biological functions. Further functional analysis of these genes demonstrates that the immune system seems to play an important role in bone-specific metastasis of breast cancer.Conclusions: Each of the dysregulated pathways that are enriched with bone metastasis related genes may uncover one critical aspect of influencing the bone metastasis of breast cancer, thus the ensemble strategy can help to describe the comprehensive view of bone metastasis mechanism. Therefore, the constructed DPBM is robust and able to significantly distinguish the bone metastases risks of patients in both test set and independent set. Moreover, the dysregulated genes in the dysregulated pathways tend to play critical roles in the biological process of bone metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China. Methods: We retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes. Results: Among the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years (P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%). Conclusion: The diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors. [ABSTRACT FROM AUTHOR]

Background: HIV disproportionately affects African-Caribbean women in Canada but the frequency and distribution of sexually transmitted infections in this community have not been previously studied.Methods: We recruited women based on HIV status through a Toronto community health centre. Participants completed a socio-behavioural questionnaire using Audio Computer Assisted Self-Interview (ACASI) and provided blood for syphilis, HIV, hepatitis B and C, herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and human cytomegalovirus (CMV) serology, urine for chlamydia and gonorrhea molecular testing and vaginal secretions for bacterial vaginosis (BV) and human papillomavirus (HPV). Differences in prevalence were assessed for statistical significance using chi-square.Results: We recruited 126 HIV-positive and 291 HIV-negative women, with a median age of 40 and 31 years, respectively (p < 0.001). Active HBV infection and lifetime exposure to HBV infection were more common in HIV-positive women (4.8% vs. 0.34%, p = 0.004; and 47.6% vs. 21.2%, p < 0.0001), as was a self-reported history of HBV vaccination (66.1% vs. 44.0%, p = 0.0001). Classical STIs were rare in both groups; BV prevalence was low and did not vary by HIV status. HSV-2 infection was markedly more frequent in HIV-positive (86.3%) than HIV-negative (46.6%) women (p < 0.0001). Vaginal HPV infection was also more common in HIV-positive than in HIV-negative women (50.8% vs. 22.6%, p < 0.0001) as was infection with high-risk oncogenic HPV types (48.4% vs. 17.3%, p < 0.0001).Conclusions: Classical STIs were infrequent in this clinic-based population of African-Caribbean women in Toronto. However, HSV-2 prevalence was higher than that reported in previous studies in the general Canadian population and was strongly associated with HIV infection, as was infection with hepatitis B and HPV. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC), as one of the commonest malignancies showing poor prognosis, has been increasingly suggested to be modulated by circular RNAs (circRNAs). Through GEO (Gene Expression Omnibus) database, a circRNA derived from ZDBF2 (circZDBF2) was uncovered to be with high expression in OSCC tissues, while how it may function in OSCC remains unclear.Methods: CircZDBF2 expression was firstly verified in OSCC cells via qRT-PCR. CCK-8, along with colony formation, wound healing, transwell and western blot assays was performed to assess the malignant cell behaviors in OSCC cells. Further, RNA pull down assay, RIP assay, as well as luciferase reporter assay was performed to testify the interaction between circZDBF2 and RNAs.Results: CircZDBF2 expressed at a high level in OSCC cells and it accelerated OSCC cell proliferation, migration, invasion as well as EMT (epithelial-mesenchymal transition) process. Further, circZDBF2 sponged miR-362-5p and miR-500b-5p in OSCC cells to release their target ring finger protein 145 (RNF145). RNF145 expressed at a high level in OSCC cells and circZDBF2 facilitated RNF145 transcription by recruiting the transcription factor CCAAT enhancer binding protein beta (CEBPB). Moreover, RNF145 activated NFκB (nuclear factor kappa B) signaling pathway and regulated IL-8 (C-X-C motif chemokine ligand 8) transcription.Conclusion: CircZDBF2 up-regulated RNF145 expression by sponging miR-362-5p and miR-500b-5p and recruiting CEBPB, thereby promoting OSCC progression via NFκB signaling pathway. The findings recommend circZDBF2 as a probable therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

Background: Syringa pinnatifolia Hemsl. is a shrub belonging to the Oleaceae family. The peeled woody stems and roots of S. pinnatifolia are used in Chinese traditional medicine. This plant has been used for centuries, and modern pharmacological research has revealed its medicinal value. However, the wild populations of S. pinnatifolia have been decreasing, and it has been listed as an endangered plant in China. To elucidate the molecular mechanism leading to the synthesis of the major components of S. pinnatifolia for its further development and sustainable use, this study compared peeled stems and twigs at the metabolic and molecular levels. Results: Peeled stems with the purple substance visible (SSP) and peeled twigs without the purple substance (TSP) were compared at different levels. Microscopic observation showed resin-like fillers in SSP and wood fiber cell walls approximately 1.0 μm thicker than those in TSP (wood fiber cell thickness approximately 2.7 μm). In addition, 104 volatile organic compounds and 870 non-volatile metabolites were detected in the non-targeted and widely-targeted metabolome analyses, respectively. Among the 76 differentially accumulated metabolites (DAMs) detected, 62 were up-accumulated in SSP. Most of these DAMs were terpenes, of which 90% were identified as sesquiterpenes in the volatile organic compound analysis. In the analysis of the non-volatile metabolites, 21 differentially accumulated lignans were identified, of which 18, including five subtypes, were accumulated in SSP. RNA sequencing revealed 4,421 upregulated differentially expressed genes (DEGs) and 5,522 downregulated DEGs in SSP compared with TSP, as well as 33,452 genes that were not differentially expressed. Analysis of the DEGs suggested that sesquiterpenes and lignans were mostly biosynthesized via the mevalonate and phenylpropanoid pathways, respectively. Additionally, in SSP, the enriched Gene Ontology terms included response to biotic stimulus and defense response, while the enriched Kyoto Encyclopedia of Genes and Genomes pathways included plant–pathogen interaction and many other pathways related to plant immunity. Conclusions: This study provides metabolome and transcriptome information for S. pinnatifolia, suggesting that biotic stimuli, including pathogens, are potential and valuable approaches to promoting the biosynthesis of the metabolites linked to the medicinal properties of this plant. [ABSTRACT FROM AUTHOR]