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Background. Network pharmacology (NP) has become an increasingly important focus in the drug research field over the past decade. However, no study to date has mapped the current status of NP. Therefore, we performed a bibliometric study to evaluate the top 100 cited papers on NP. Methods. We searched the Web of Science Core Collection from its inception to February 25, 2019, using the terms "network pharmacology" and "systems pharmacology." Key data, including title, publication year, number of citations, authors, countries/regions, organizations, and journals, were retrieved and analyzed using Excel 2016 and VOSviewer 1.6.10. Results. The total number of citations for the 100 cited papers ranged from 21 to 1,238, published in 53 journals, from 2005 to 2017. The top three journals with the most publications on NP were Clinical Pharmacology & Therapeutics (n = 8, IF2017 = 6.544), Journal of Ethnopharmacology (n = 8, IF2017 = 3.115), and PLoS One (n = 7, IF2017 = 2.766). Most published articles were from the USA (n = 41) and China (n = 35). The most active author was Wang Yonghua from the Northwest A&F University, and of the 100 publications, 14 listing his name. The most frequently used substantive terms included "drug discovery," "traditional Chinese medicine (TCM)," "in-vitro," "cancer," and "cardiovascular disease." Conclusions. The USA and China made the greatest contribution to NP research. The current NP research mainly focused on NP methods (including experimental validation) and using them to explore the molecular mechanisms of TCM for some critical diseases such as cardiovascular diseases and cancers. Furthermore, we believe some guidelines should be developed to regulate NP studies. [ABSTRACT FROM AUTHOR]

The MYB transcription factor family is one of the largest families of plant transcription factors (TFs), and it plays a vital role in the entire process of a plant's growth and development. Well known in China, Eucommia ulmoides (E. ulmoides) produces a form of natural rubber called Eucommia ulmoides gum (EUG). Nevertheless, there is little research on the evolutionary history and expression patterns of its MYBs, as well as on the regulation of EUG by MYB TFs. This research provides a comprehensive description, classification, and potential functional analysis of the EuMYB gene family. A total of 119 MYB members of E. ulmoides were identified based on the whole genome sequencing data, and their gene structure, phylogenetics, chromosome location, conserved motifs, etc., were analyzed. Based on the phylogenetic tree results, EuMYBs could be divided into 35 sub-groups. In addition, chromosomal localization and collinearity analysis revealed the heterogeneous distribution of the MYB family in the E. ulmoides' genome, indicating the expansion of its gene family. Moreover, promoter cis-acting elements showed that the promoter contained abundant light-responsive elements, anaerobic-induction-responsive elements, and abscisic-acid-responsive elements. A co-expression regulatory network between the EUG biosynthesis genes and the EuMYBs was built. Meanwhile, regarding the six EuMYBs with high expression in the gum-forming tissues selected that correlated with the farnesyl diphosphate synthase (FPS1) structural gene, RT-qPCR experiments showed a possible regulatory relationship between EuMYBs and FPS1, which played an important role in EUG biosynthesis. In conclusion, this paper defines a research gap and lays a foundation for further studies on the biological functions of EuMYBs. [ABSTRACT FROM AUTHOR]

Aiming at the problem of depression recognition, this paper proposes a computer-aided recognition framework based on decision-level multimodal fusion. In Song Dynasty of China, the idea of multimodal fusion was contained in “one gets different impressions of a mountain when viewing it from the front or sideways, at a close range or from afar” poetry. Objective and comprehensive analysis of depression can more accurately restore its essence, and multimodal can represent more information about depression compared to single modal. Linear electroencephalography (EEG) features based on adaptive auto regression (AR) model and typical nonlinear EEG features are extracted. EEG features related to depression and graph metric features in depression related brain regions are selected as the data basis of multimodal fusion to ensure data diversity. Based on the theory of multi-agent cooperation, the computer-aided depression recognition model of decision-level is realized. The experimental data comes from 24 depressed patients and 29 healthy controls (HC). The results of multi-group controlled trials show that compared with single modal or independent classifiers, the decision-level multimodal fusion method has a stronger ability to recognize depression, and the highest accuracy rate 92.13% was obtained. In addition, our results suggest that improving the brain region associated with information processing can help alleviate and treat depression. In the field of classification and recognition, our results clarify that there is no universal classifier suitable for any condition. [ABSTRACT FROM AUTHOR]

Acupuncture is an important part of Chinese medicine that has been widely used in the treatment of inflammatory diseases. During the coronavirus disease 2019 (COVID-19) epidemic, acupuncture has been used as a complementary treatment for COVID-19 in China. However, the underlying mechanism of acupuncture treatment of COVID-19 remains unclear. Based on bioinformatics/topology, this paper systematically revealed the multi-target mechanisms of acupuncture therapy for COVID-19 through text mining, bioinformatics, network topology, etc. Two active compounds produced after acupuncture and 180 protein targets were identified. A total of 522 Gene Ontology terms related to acupuncture for COVID-19 were identified, and 61 pathways were screened based on the Kyoto Encyclopedia of Genes and Genomes. Our findings suggested that acupuncture treatment of COVID-19 was associated with suppression of inflammatory stress, improving immunity and regulating nervous system function, including activation of neuroactive ligand–receptor interaction, calcium signaling pathway, cancer pathway, viral carcinogenesis, Staphylococcus aureus infection, etc. The study also found that acupuncture may have additional benefits for COVID-19 patients with cancer, cardiovascular disease and obesity. Our study revealed for the first time the multiple synergistic mechanisms of acupuncture on COVID-19. Acupuncture may play an active role in the treatment of COVID-19 and deserves further promotion and application. These results may help to solve this pressing problem currently facing the world. [ABSTRACT FROM AUTHOR]

Sophora tonkinensis Gagnep. (ST) (Fabaceae) is distributed chiefly in south-central and southeast China and Vietnam. In traditional Chinese medicine theory, the root and rhizome of ST are toxic and mainly used in the treatment of pharyngeal and laryngeal diseases. Modern studies provide new insights into the pharmacological and toxicological aspects of ST. The pharmacological and toxicological properties of ST were reviewed in this paper based on the literature from Google Scholar and CNKI, and the bioinformatics platforms were applied to explore the pharmacological and toxicological potentials of ST. The results of the literature analysis showed that ST has hepatoprotective, immunomodulatory, and anticancer effects and produces obvious toxicity to the liver and nervous and cardiovascular system. The results of bioinformatics showed that the compounds from ST may be applied to the treatment of cancer and digestive and nervous system diseases and show the possibility to cause hematotoxicity, neurotoxicity, and immunotoxicity. The present review demonstrates that attention should be paid to the potential toxicity of ST in the treatment of diseases and provides the reference for the subsequent pharmacological toxicological studies on the mechanism and chemical basis of ST. [ABSTRACT FROM AUTHOR]

Background Newborn genetic screening (NBGS) is promising for early detection of genetic diseases in newborns. However, little is known about its clinical effectiveness in special groups like high-risk infants. To address this gap, we aimed to investigate the impact of NBGS on high-risk infants. Methods We screened 10 334 healthy newborns from the general maternity unit and 886 high-risk infants from the neonatal ward using both traditional newborn screening (tNBS) and NBGS, and collected clinical data from electronic medical records. Results We found that high-risk infants had a higher proportion of eutocia (P < 0.01) and prematurity (P < 0.01). For high-risk infants vs healthy newborns screened by tNBS, the primary screening positive rate was 3.84% vs 1.31%, the false positive rate (FPR) was 3.62% vs 1.18% (P < 0.001), and the positive predictive value (PPV) was 5.88% vs 8.27%. For NBGS vs tNBS in high-risk infants, the primary screening positive rate was 0.54% vs 3.68%, the FPR was 0.22% vs 3.47%, and the PPV was 60.00% vs 5.88%. Conclusions We found that combined newborn screening can effectively reduce the FPR caused by the high-risk symptoms and improve the PPV in high-risk infants, sufficient for more accurately showing the true status of the disease. [ABSTRACT FROM AUTHOR]

To balance the supply and demand in China's beef market, beef consumption must be scientifically and effectively forecasted. Beef consumption is affected by many factors and is characterized by gray uncertainty. Therefore, gray theory can be used to forecast the beef consumption, In this paper, the structural defects and unreasonable parameter design of the traditional gray model are analyzed. Then, a new gray model termed, EGM(1,1,r), is built, and the modeling conditions and error checking methods of EGM(1,1,r) are studied. Then, EGM(1,1,r) is used to simulate and forecast China’s beef consumption. The results show that both the simulation and prediction precisions of the new model are better than those of other gray models. Finally, the new model is used to forecast China’s beef consumption for the period from 2019–2025. The findings will serve as an important reference for the Chinese government in formulating policies to ensure the balance between the supply and demand for Chinese beef. [ABSTRACT FROM AUTHOR]

Despite the outstanding technological advances achieved in the last few decades, infectious diseases remain a major societal challenge. From the variolation carried out in ancient China during the 15th century to the more advanced RNA and DNA vaccines presently available, vaccines have been proven as highly effective therapeutic tools to combat various infectious diseases. Vaccine research and development is now empowered with recent advances in Omics sciences and the developments of powerful bioinformatics tools. This Special Issue has gathered a total of nine original papers, including seven research papers and two reviews, illustrating the use of Omics data and bioinformatics in the research, design and development of vaccines against pathogens and cancer. The integration of knowledge from Omics and Bioinformatics will certainly boost vaccine research and development, leading to novel therapeutic tools against new and old pathogens and cancer in the near future. [ABSTRACT FROM AUTHOR]

Background: while most gut microbiota research has focused on term infants, the health outcomes of preterm infants are equally important. Very-low-birth-weight (VLBW) or extremely-low-birth-weight (ELBW) preterm infants have a unique gut microbiota structure, and probiotics have been reported to somewhat accelerate the maturation of the gut microbiota and reduce intestinal inflammation in very-low preterm infants, thereby improving their long-term outcomes. The aim of this study was to investigate the structure of gut microbiota in ELBW neonates to facilitate the early identification of different types of low-birth-weight (LBW) preterm infants. Methods: a total of 98 fecal samples from 39 low-birth-weight preterm infants were included in this study. Three groups were categorized according to different birth weights: ELBW (n = 39), VLBW (n = 39), and LBW (n = 20). The gut microbiota structure of neonates was obtained by 16S rRNA gene sequencing, and microbiome analysis was conducted. The community state type (CST) of the microbiota was predicted, and correlation analysis was conducted with clinical indicators. Differences in the gut microbiota composition among ELBW, VLBW, and LBW were compared. The value of gut microbiota composition in the diagnosis of extremely low birth weight was assessed via a random forest-machine learning approach. Results: we briefly analyzed the structure of the gut microbiota of preterm infants with low birth weight and found that the ELBW, VLBW, and LBW groups exhibited gut microbiota with heterogeneous compositions. Low-birth-weight preterm infants showed five CSTs dominated by Enterococcus, Staphylococcus, Klebsiella, Streptococcus, Pseudescherichia, and Acinetobacter. The birth weight and clinical indicators related to prematurity were associated with the CST. We found the composition of the gut microbiota was specific to the different types of low-birth-weight premature infants, namely, ELBW, VLBW, and LBW. The ELBW group exhibited significantly more of the potentially harmful intestinal bacteria Acinetobacter relative to the VLBW and LBW groups, as well as a significantly lower abundance of the intestinal probiotic Bifidobacterium. Based on the gut microbiota's composition and its correlation with low weight, we constructed random forest model classifiers to distinguish ELBW and VLBW/LBW infants. The area under the curve of the classifiers constructed with Enterococcus, Klebsiella, and Acinetobacter was found to reach 0.836 by machine learning evaluation, suggesting that gut microbiota composition may be a potential biomarker for ELBW preterm infants. Conclusions: the gut bacteria of preterm infants showed a CST with Enterococcus, Klebsiella, and Acinetobacter as the dominant genera. ELBW preterm infants exhibit an increase in the abundance of potentially harmful bacteria in the gut and a decrease in beneficial bacteria. These potentially harmful bacteria may be potential biomarkers for ELBW preterm infants. [ABSTRACT FROM AUTHOR]

The increasing importance of computational techniques in post-genomic life science research calls for new forms and combinations of expertise that cut across established disciplinary boundaries between computing and biology. These are most marked in large scale gene sequencing facilities. Here new ways of organising knowledge production, drawing on industrial models, have been perceived as pursuing efficiency and control to the potential detriment of academic autonomy and scientific quality. We explore how these issues are played out in the case of BGI (Beijing Genomics Institute prior to 2008). BGI (in Pinyin, Hua Da Jiyin– Big China Genome) is today the world's largest centre for gene sequencing research. Semi-detached from traditional academic institutions, BGI has developed distinctive models for organising research and for developing expertise, informed by practices in US Information Technology and Life Science Laboratories, that differ from existing models of interdisciplinary research in academic institutions. [ABSTRACT FROM AUTHOR]

Rainbow trout (Oncorhynchus mykiss) is a significant cold-water fish farmed in China. Currently, most molecular marker-assisted breeding applications in rainbow trout rely on SSR markers. Although many rainbow trout SSR markers have been developed, methods for mining many polymorphic SSR markers from the genome and identifying them efficiently and rapidly are still lacking. For this reason, this study used in silico simulation method to rapidly develop a large number of polymorphic SSR markers quickly. A total of 354,613 SSR loci with two to six nucleotide repeat motifs were mined from 32 chromosomes of the rainbow trout reference genome using GMATA. The chromosome sequences of the reference genome were then aligned to the whole genome sequencing data (10×) of 68 rainbow trout samples. In silico genotyping was performed using the HipSTR programme to compare and count the variation in the number of repeats of the motifs of the SSR loci in the samples. The loci with high deletion rates and monomorphism were discarded, while those with more than one nonreference allele were kept. The final set of polymorphic SSR loci screened was 78,828. Finally, 4,821 SSR loci were selected with more than 3 alleles and no deletion in all rainbow trout samples and were physically mapped. The average polymorphic information content of these loci was 0.692, indicating high levels of polymorphism. These SSRs were utilized to analyse the genetic diversity and population structure of the 68 rainbow trout samples. The results showed that these 68 samples were divided into two groups. These newly discovered polymorphic SSR markers will provide valuable information for evaluating the construction of rainbow trout family lines for genetic diversity and improvement. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is known to play a crucial role in diabetic osteopathy. However, key genes and molecular mechanisms remain largely unclear. This study aimed to identify a crucial ferroptosis-related differentially expressed gene (FR-DEG) in diabetic osteopathy and investigate its potential mechanism. Methods: We identified fibronectin type III domain-containing protein 5 (FNDC5)/irisin as an essential FR-DEG in diabetic osteopathy using the Ferroptosis Database (FerrDb) and GSE189112 dataset. Initially, a diabetic mouse model was induced by intraperitoneal injection of streptozotocin (STZ), followed by intraperitoneal injection of irisin. MC3T3-E1 cells treated with high glucose (HG) were used as an in vitro model. FNDC5 overexpression plasmid was used to explore underlying mechanisms in vitro experiments. Femurs were collected for micro-CT scan, histomorphometry, and immunohistochemical analysis. Peripheral serum was collected for ELISA analysis. Cell viability was assessed using a CCK-8 kit. The levels of glutathione (GSH), malondialdehyde (MDA), iron, reactive oxygen species (ROS), and lipid ROS were detected by the corresponding kits. Mitochondria ultrastructure was observed through transmission electron microscopy (TEM). Finally, mRNA and protein expressions were examined by quantitative real‐time PCR (qRT‐PCR) and western blot analysis. Results: The expression of FNDC5 was found to be significantly decreased in both in vivo and in vitro models. Treatment with irisin significantly suppressed ferroptosis and improved bone loss. This was demonstrated by reduced lipid peroxidation and iron overload, increased antioxidant capability, as well as the inhibition of the ferroptosis pathway in bone tissues. Furthermore, in vitro studies demonstrated that FNDC5 overexpression significantly improved HG-induced ferroptosis and promoted osteogenesis. Mechanistic investigations revealed that FNDC5 overexpression mitigated ferroptosis in osteoblasts by inhibiting the eukaryotic initiation factor 2 alpha (eIF2α)/activated transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) pathway. Conclusions: Collectively, our study uncovered the important role of FNDC5/irisin in regulating ferroptosis of diabetic osteopathy, which might be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

aimen District People's Hospital, Nantong, Jiangsu Province, 226100, People's Republic of China Correspondence: Shangqi Chu, Department of Medical Oncology, Nantong Haimen District People's Hospital, Nantong, Jiangsu Province, 226100, People's Republic of China, Tel/Fax +86-513-82263620, Email [email protected] Background: This study aims to investigate the clinicopathological significance and prognostic value of Trichohyalin (TCHH) in gastric cancer patients through bioinformatics analysis. Materials and Methods: Data on TCHH expression and clinicopathological information were sourced from The Cancer Genome Atlas (TCGA). The Wilcoxon signed-rank test was used for evaluating the correlation between TCHH mRNA expression levels and clinicopathological features. The predictive significance of TCHH mRNA expression for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in patients with gastric cancer was assessed using Cox regression models. Furthermore, measures of immune cell infiltration in gastric cancer were made, and studies of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were also carried out to investigate the possible roles of TCHH in patients with gastric cancer. Results: Compared to normal tissues, gastric cancer had a considerably higher expression of TCHH mRNA (P < 0.05). Wilcoxon analysis revealed a significant association between TCHH mRNA expression and the pathologic M stage (P = 0.017). High TPMT mRNA levels were also correlated with worse OS, DFS, and PFI in gastric cancer patients (both P < 0.05). TCHH showed significant negative correlations with the levels of NK CD56dim infiltration (r = − 0.157, p = 0.002), Th17 cells infiltration (r = − 0.235, P < 0.001), and Th2 infiltration (r = − 0.195, P < 0.001). Furthermore, enrichment analysis indicated potential involvement in intermediate filament cytoskeleton organization, DNA methylation in gamete generation, cell-cell recognition, and G protein-coupled peptide receptor (GPCRs) activity. Conclusion: The level of TCHH mRNA may serve as a novel prognostic biomarker for gastric cancer patients. [ABSTRACT FROM AUTHOR]

Objective: This paper shall first investigate the informatics areas and applications of the four Traditional Medicine systems - Traditional Chinese Medicine (TCM), Ayurveda, Traditional Arabic and Islamic Medicine and Traditional Malay Medicine. Then, this paper shall examine the national informatics infrastructure initiatives in the four respective countries that support the Traditional Medicine systems. Challenges of implementing informatics in Traditional Medicine Systems shall also be discussed.Methods: The literature was sourced from four databases: Ebsco Host, IEEE Explore, Proquest and Google scholar. The search term used was "Traditional Medicine", "informatics", "informatics infrastructure", "traditional Chinese medicine", "Ayurveda", "traditional Arabic and Islamic medicine", and "traditional malay medicine". A combination of the search terms above was also executed to enhance the searching process. A search was also conducted in Google to identify miscellaneous books, publications, and organization websites using the same terms.Results: Amongst major advancements in TCM and Ayurveda are bioinformatics, development of Traditional Medicine databases for decision system support, data mining and image processing. Traditional Chinese Medicine differentiates itself from other Traditional Medicine systems with documented ISO Standards to support the standardization of TCM. Informatics applications in Traditional Arabic and Islamic Medicine are mostly ehealth applications that focus more on spiritual healing, Islamic obligations and prophetic traditions. Literature regarding development of health informatics to support Traditional Malay Medicine is still insufficient. Major informatics infrastructure that is common in China and India are automated insurance payment systems for Traditional Medicine treatment. National informatics infrastructure in Middle East and Malaysia mainly cater for modern medicine. Other infrastructure such as telemedicine and hospital information systems focus its implementation in modern medicine or are not implemented and strategized at a national level to support Traditional Medicine.Conclusion: Informatics may not be able to address all the emerging areas of Traditional Medicine because the concepts in Traditional Medicine system of medicine are different from modern system, though the aim may be same, i.e., to give relief to the patient. Thus, there is a need to synthesize Traditional Medicine systems and informatics with involvements from modern system of medicine. Future research works may include filling the gaps of informatics areas and integrate national informatics infrastructure with established Traditional Medicine systems. [ABSTRACT FROM AUTHOR]

BACKGROUND Catheter-based pulmonary vein isolation (PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation (PAF). Nevertheless, late recurrences of atrial fibrillation (LRAF) occurring during 3 to 12 months are common, and the underlying mechanisms remain elusive. Circular RNAs (circRNAs) in atrial tissue have been linked to the pathophysiological mechanisms and progression of PAF in a few studies. However, their expression patterns in peripheral blood and regulatory function in LRAF are not clear. METHODS In the present study, the expression profile of circulating circRNAs in three paired nonvalvular PAF patients with or without LRAF was investigated by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA/miRNA regulatory network, were performed to predict the functions and potential regulatory roles of differentially expressed (DE) circRNAs. RESULTS A total of 12,834 circRNAs, comprising 5,491 down-regulated and 7,343 up-regulated circRNAs, were found to be DE in blood smaples from the two groups in peripheral blood between LRAF and non-recurrence control individuals. The most enriched GO categories in terms of molecular function, biological process, and cellular component features were catalytic activity, cellular metabolic process, and intracellular part, respectively. The KEGG enrichment study revealed that the most important metabolic process controlled by DE circRNAs is endocytosis. In the circRNA/microRNAs interaction network, four up-regulated circRNAs (hsa_circ_0002665, hsa_circ_0001953, hsa_circ_0003831, and hsa_circ_0040533) and one down-regulated circRNA (hsa_circ_0041103) were predicted to play potential regulatory roles in the pathogenesis of LRAF. CONCLUSIONS This investigation discovered the expression pattern of circulating circRNAs that is indicative of PAF late recurrence, which may serve as risk markers or therapeutic targets for LRAF after PVI. [ABSTRACT FROM AUTHOR]

The emergence of the COVID-19 pandemic in Wuhan in 2019 led to the discovery of a novel coronavirus. The World Health Organization (WHO) designated it as a global pandemic on 11 March 2020 due to its rapid and widespread transmission. Its impact has had profound implications, particularly in the realm of public health. Extensive scientific endeavors have been directed towards devising effective treatment strategies and vaccines. Within the healthcare and medical imaging domain, the application of artificial intelligence (AI) has brought significant advantages. This study delves into peer-reviewed research articles spanning the years 2020 to 2022, focusing on AI-driven methodologies for the analysis and screening of COVID-19 through chest CT scan data. We assess the efficacy of deep learning algorithms in facilitating decision making processes. Our exploration encompasses various facets, including data collection, systematic contributions, emerging techniques, and encountered challenges. However, the comparison of outcomes between 2020 and 2022 proves intricate due to shifts in dataset magnitudes over time. The initiatives aimed at developing AI-powered tools for the detection, localization, and segmentation of COVID-19 cases are primarily centered on educational and training contexts. We deliberate on their merits and constraints, particularly in the context of necessitating cross-population train/test models. Our analysis encompassed a review of 231 research publications, bolstered by a meta-analysis employing search keywords (COVID-19 OR Coronavirus) AND chest CT AND (deep learning OR artificial intelligence OR medical imaging) on both the PubMed Central Repository and Web of Science platforms. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Fructus Ligustri Lucidi (FLL) has been used for premature graying of hair since ancient China and is currently used to treat vitiligo. However, the key biomarkers and mechanisms underlying FLL in vitiligo remain unclear. This study aimed to identify the potential biomarkers and mechanisms of FLL in vitiligo using network pharmacology analysis.Methods: The expression profiles of GSE65127 and GSE75819 were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between the vitiligo and healthy samples. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs were performed using R analyses. We performed R to further understand the functions of the critical targets. Cytoscape tools have facilitated network topology analysis. Molecular docking was performed using Auto Dock Vina software.Results: The results showed that 13 DEGs were screened in vitiligo. Based on bioinformatics, network pharmacology and Western blot, we found that the critical targets of melanoma antigen recognized by 5,6-dihydroxyindole-2-carboxylic acid oxidase (TYRP1) may be related to the mechanism of action of FLL in the treatment of vitiligo.Conclusion: TYRP1, as a melanocyte molecular biomarker, may be closely related to the underlying mechanism of FLL in the treatment of vitiligo via the inhibition of melanocyte death. [ABSTRACT FROM AUTHOR]

Background: The mortality of cervical cancer (CC) is quite high and advanced CC is hard to cure. Accordingly, to find the mechanism of CC progression at molecular level is imminent. Methods: The mRNA expression data were acquired from The Cancer Genome Atlas database, and squalene epoxidase (SQLE) level in the tumor and adjuvant tissues of CC was analyzed. The pathway enrichment analysis of target mRNAs was performed based on the GSEA database. The cancerous tissues and para‐cancerous tissues of CC patients were collected for immunohistochemistry. SQLE and p53 mRNA expression was ensured by qRT‐polymerase chain reaction. SQLE and p53 protein levels were determined by western blot. Cell functional assays focused on evaluating the malignant behaviors of cancer cells in each treatment group. Nude mouse xenograft models were constructed for tumorigenicity analysis. Results: Bioinformatics analysis revealed that SQLE expression was high in CC tissues, which was linked to the poor prognosis. SQLE could affect the p53 signaling pathway. Cell functional assays demonstrated that SQLE expression was promoted in CC cell lines, and overexpressing SQLE facilitated the malignant phenotypes of CC cells, whereas silencing SQLE suppressed CC progression in vitro and in vivo. Besides, the repressed p53 signaling pathway could reverse the effect caused by silenced SQLE. Conclusion: SQLE could promote CC progression by modulating the p53 signaling pathway. [ABSTRACT FROM AUTHOR]

(1) Rhododendron is one of the top ten traditional flowers in China, with both high ornamental and economic values. However, with the change of the environment, Rhododendron suffers from various biological stresses. The WRKY transcription factor is a member of the most crucial transcription factor families, which plays an essential regulatory role in a variety of physiological processes and developmental stresses. (2) In this study, 57 RsWRKYs were identified using genome data and found to be randomly distributed on 13 chromosomes. Based on gene structure and phylogenetic relationships, 57 proteins were divided into three groups: I, II, and III. Multiple alignments of RsWRKYs with Arabidopsis thaliana homologous genes revealed that WRKY domains in different groups had different conserved sites. RsWRKYs have a highly conserved domain, WRKYGQK, with three variants, WRKYGKK, WRKYGEK, and WRKYGRK. Furthermore, cis-acting elements analysis revealed that all of the RsWRKYs had stress and plant hormone cis-elements, with figures varying by group. Finally, the expression patterns of nine WRKY genes treated with gibberellin acid (GA), methyl jasmonate (MeJA), heat, and drought in Rhododendron were also measured using quantitative real-time PCR (qRT-PCR). The results showed that the expression levels of the majority of RsWRKY genes changed in response to multiple phytohormones and abiotic stressors. (3) This current study establishes a theoretical basis for future studies on the response of RsWRKY transcription factors to various hormone and abiotic stresses as well as a significant foundation for the breeding of new stress-tolerant Rhododendron varieties. [ABSTRACT FROM AUTHOR]

Simple Summary: Inflammation has been recognized as one of the hallmarks of cancers. PYCARD, the adaptor protein of inflammasomes, plays an important role in pyroptosis and apoptosis. However, the function of PYCARD remains unclear in human cancers. Here, we systematically performed a comprehensive analysis of PYCARD expression and its relationship with immunotherapy response and prognosis. We found significant differences in PYCARD expression between tumor and normal tissue, particularly in clear cell renal cell carcinoma. We also found that PYCARD was an unfavorable prognostic factor and was confirmed by external validation cohorts. Exploration of the profound mechanisms of PYCARD might help to identify new therapeutic targets and improve the efficacy of immunotherapy. PYCARD is a protein engaged in inflammation, pyroptosis, and apoptosis. However, the function of PYCARD in human cancers remains unclear. The objective of our study was to explore PYCARD expression and prognostic value in human cancers. Public databases were used to assess PYCARD expression and prognostic value. The TISIDB database was used to explore the associations between PYCARD expression and different immune subtypes. The correlations between PYCARD expression and ICP genes, MMR genes, MSI, and TMB were also investigated. The immunotherapy response was assessed using the TIDE database. Single-cell RNA databases evaluated the PYCARD expression of immune cells. External datasets and immunohistochemical staining were conducted to validate PYCARD expression and prognostic value. The results showed that PYCARD expression varied in several cancers and was associated with prognosis, immune-related genes, published biomarkers, and immunotherapy response. Of note, PYCARD expression was upregulated in renal cancers with high diagnostic ability. Upregulation of PYCARD was correlated with worse prognosis in KIRC and external validation cohorts. In conclusion, PYCARD demonstrated strong correlations with prognosis, immune response, and disease progression in pan-cancer analysis. In ccRCC, PYCARD might serve as a biomarker for diagnosis and therapeutic target-boosting immunotherapy response. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the associations between traditional Chinese medicine (TCM) syndromes and driver gene mutations as well as the clinical characteristics of patients with lung adenocarcinoma. We performed a cross-sectional study in patients with lung adenocarcinoma between June 2020 and October 2021. The patient characteristics, such as age, sex, smoking history, clinical stage, metastasis, driver gene mutations, and the type of traditional Chinese medicine syndrome/element, were collected. The associations between each TCM syndrome and sex, smoking history, clinical stage, metastasis, and driver gene mutations were analyzed. The present study included 127 patients. The most frequent TCM syndromes were Qi and Yin deficiency (39, 30.7%) and lung-spleen Qi deficiency (32, 25.2%). Eighty-one (63.8%) patients had mutations in driver genes, especially in the EGFR gene (64, 79.0%). There was a statistically significant association between a driver gene mutation and TCM syndrome (P < 0.05). Genetic mutations presented more frequently in patients with Qi and Yin deficiency (37.0%), lung-spleen Qi deficiency (30.0%), or the cold element (59.3%). Male patients were more likely to have Qi stagnation and blood stasis, whereas female patients were more likely to have lung-spleen Qi deficiency or Qi and Yin deficiency. The patients with lung-spleen Qi deficiency were usually younger than those with Qi and Yin deficiency or Qi stagnation and blood stasis (P < 0.05). Compared with the patients with other TCM syndromes, the patients with Yin and Yang deficiency were more likely to have bone metastasis. TCM syndromes were associated with driver gene mutations, sex, age, and bone metastasis in patients with lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background. Chronic sinusitis (CRS) was a chronic inflammation that originated in the nasal mucosa and affected the health of most people around the world. Chronic rhinosinusitis with nasal polyps (CRSwNP) was one kind of chronic sinusitis. Emerging research had suggested that long noncoding RNAs (lncRNAs) played vital parts in inflammatories and inflammation development. Methods. We acquired GEO data to analyze the differential expression between the miRNA, immune genes, TF, and lncRNA data in CRSWNP and the corresponding control tissues. Bioinformatic analysis by coexpression of endogenous RNA network and competitive way enrichment, analysis, and forecasting functions of these noncoding RNA. The different pathway expressions in CRSwNP patients were confirmed using GSVA to analyze the differentially expressed immune genes and TF data sets in CRSwNP patients. The differential immune gene and transcription factor data set in CRSwNP perform functional notes and protein-protein interaction (PPI) network structure. We predicted the potential genes and RNAs related to CRSWNP by constructing a ceRNA network. In addition, we also used 19 hub immune genes to predict the potential drugs of CRSWNP. lncRNA biomarkers in CRSwNP were identified by lncRNAs LASSO regression. The CIBERSORT algorithm was used to contrast the divergence in immune infiltrations between CRSwNP and usual inferior turbinate organizations in 22 immunocyte subgroups. Results. We identified a total of 48 miRNAs, 304 lncRNAs, 92 TFs, and 525 immune genes as CRSwNP-specific RNAs. GO and KEGG pathways both analyzed differentially expressed immune genes and transcription factor data sets. We predicted the potential genes GNG7, TUSC8, LINC01198, and has-miR-6776-5p by constructing ceRNA and PPI networks. At the same time, we found that the above genes were involved in two important pathways: chemokine signal path and PI3K/AKT signal path. In addition, we predicted 5 small molecule drugs to treat CRSwNP by analyzing 19 central immune genes, namely, danazol, ikarugamycin, semustine, cefamandole, and molindone. Finally, we identified 5 biomarkers in CRSwNP, namely, LINC01198, LINC01094, LINC01798, LINC01829, and LINC01320. Conclusions. We had identified CRSwNP-related miRNAs, lncRNAs, TFs, and immune genes, which may be making use of latent therapeutic target for CRSwNP. At the same time, we identified 5 lncRNA biomarkers in CRSwNP. The results of this study showed that LINC01198 promoted the progression of CRSwNPs through spongy miR-6776-5p. Our studies provide a new way for further analyses of the pathogenesis of CRSwNP. [ABSTRACT FROM AUTHOR]

Background. Brugada syndrome is a hereditary cardiac disease associated with mutations in ion channel genes. The clinical features include ventricular fibrillation, syncope, and sudden cardiac death. A family with Brugada syndrome with sudden cardiac death was analyzed to locate the associated mutation in the SCN5A gene. Methods and Results. Three generations of a Han Chinese family with Brugada syndrome were recruited in the study; their clinical phenotype data were collected and DNA samples extracted from the peripheral blood. Next-generation sequencing was carried out in the proband, and candidate genes and mutations were screened using the full exon capture technique. The family members who participated in the survey were tested for possible mutations using Sanger sequencing. Six family members were diagnosed with Brugada syndrome, including four asymptomatic patients. A newly discovered heterozygous mutation in the proband was located in exon 25 of SCN5A (NM_000335.5) at c.4313dup(p.Trp1439ValfsTer32). Among the surviving family members, only those with a Brugada wave on their electrocardiogram carried the c.4313dup(p.Trp1439ValfsTer32) variant. Bioinformatics prediction revealed that the frameshift of the c.4313dup (p.Trp1439ValfsTer32) mutant led to a coding change of 32 amino acids, followed by a stop codon, resulting in a truncated protein product. Conclusion. The newly discovered mutation site c.4313dup(p.Trp1439ValfsTer32) in exon 25 of SCN5A may be the molecular genetic basis of the family with Brugada syndrome. [ABSTRACT FROM AUTHOR]

Objectives: Recurrent aphthous ulcer (RAU) is a common oral disease with unclear mechanism. This study aimed to explore the serum signatures of RAU patients via proteomic and transcriptomic analysis. Methods: This study was based on clinical observation. Part of serum was used for clinical tests, while the rest was processed for isobaric tags for relative and absolute quantitation (ITRAQ) labeling coupled with two‐dimensional liquid chromatography–tandem mass spectrometry (2D LC‐MS/MS) combined with microRNA (miRNA) microarrays. Bioinformatic analysis was then used to obtain significant signatures, which was verified by ELISA, qRT‐PCR, and dual‐luciferase reporter gene assays. Results: Clinical data showed that triglyceride level, white blood cell count, and neutrophils percentage were increased in RAU group, while lymphocytes percentage was decreased. ITRAQ‐2D LC‐MS/MS identified 22 upregulated and 33 downregulated proteins in RAU group. Simultaneously, miRNA microarrays identified 64 upregulated and 31 downregulated miRNAs. After integrative bioinformatic analysis and verification, three miRNA‐protein pairs, mainly involved in oxidative stress and inflammation responses, were obtained. Additionally, the interaction network indicated the crucial role of complement and coagulation cascade pathway in RAU. Conclusions: Our study revealed that complement and coagulation cascade pathway, oxidative stress, and inflammation responses may act as vital factors in pathogenesis of RAU. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) participate in the comprehensive biological process of several cancer types. In our former study, we found that hsa-microRNA- (miR-)28-5p was downregulated, but tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activating protein zeta (14-3-3ζ or YWHAZ) was upregulated in diffuse large B-cell lymphoma (DLBCL) tissues. We predicted that YWHAZ was a target gene for hsa-miR- 28-5p using bioinformatics analysis. Our goal was to reveal the role of hsa-miR-28-5p in DLBCL. YWHAZ was tested by immunohistochemistry (IHC) in formalin-fixed paraffin-embedded (FFPE) tissues of 137 DLBCL tissues, and the expression of hsa-miR-28-5p and YWHAZ was examined by quantitative real-time polymerase chain reaction (qRT-PCR) in 15 fresh and frozen DLBCL tissues. To study the functional roles of the downregulated hsa-miR-28-5p in DLBCL, a Cell Counting Kit-8 assay was conducted to estimate cell proliferation. Transient transfection of miRNA mimics was performed to overexpress hsa-miR-28-5p, and flow cytometry was performed to examine cell apoptosis and cell cycle progression. A dual-luciferase reporter assay was employed to explore the relationship between hsa-miR-28-5p and YWHAZ. Western blotting and qRT-PCR were used to investigate the function of hsa-miR-28-5p in YWHAZ expression. hsa-miR-28-5p was found to be significantly downregulated in DLBCL tissues and cell lines. Functional studies showed that hsa-miR-28-5p overexpression inhibited cell viability and proliferation, and YWHAZ was predicted to be a target of hsa-miR-28-5p. Dual-luciferase reporter assay, Western blotting, and qRT-PCR verified that hsa-miR-28-5p negatively regulated YWHAZ expression by directly targeting its 3′ untranslated regions in DLBCL cells. hsa-miR-28-5p may suppress the growth of DLBCL cells by inhibiting YWHAZ expression. These findings could provide novel targets for DLBCL diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Background. With the advent of ageing population, osteoporosis (OP) has already become a global challenge. Jintiange capsule is extensively applied to treat OP in China. Although recent studies demonstrate that it generates significant effects on strengthening bone, the exact mechanism of the jintiange capsule for treating OP remains unknown. Purpose. To understand the main ingredients of the jintiange capsule, predict the possible targets and the relevant signal transduction pathways, and explore the mechanism of the jintiange capsule for the treatment of OP. Methods. Main ingredients of the jintiange capsule, drug targets, and potential disease targets for OP were obtained from public databases. Molecular biological processes and signaling pathways were determined via bioinformatic analysis, containing protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the disease-drug-ingredient-targets-pathways networks were constructed using Cytoscape. According to CytoNCA, core targets were acquired. Finally, the present study conducted molecular docking for better testing the abovementioned results. Results. In the current work, we found that 4 main ingredients of the jintiange capsule, 33 drug targets, 4745 potential disease targets for OP, and 12 overlapping targets were identified. PPI network containing 12 nodes and 25 edges proved that there existed a complex relationship. As revealed by GO functional annotation, the intersected targets were mostly associated with BP, CC, and MF. The targets were enriched to 368 items in BP, 27 items in CC, and 42 items in MF. They mainly included calcium ion homeostasis, calcium channel complex, and calcium channel regulator activity. According to KEGG pathway analysis, the intersected targets were mostly associated with Rap 1, cGMP-PKG, Ras, cAMP, calcium pathways, and so on. Based on the analysis with CytoNCA, we acquired 4 core targets, respectively—CALR, SPARC, CALM1, and CALM2. Besides, 2 core targets, CALR and CALM1, were selected for molecular docking experiments. Molecular docking revealed that the main ingredient, calcium phosphate, had good binding with the CALR protein and CALM1 protein. Conclusion. To conclude, the main ingredient of the jintiange capsule, particularly calcium phosphate, may interact with 2 targets, CALR and CALM1, and regulate multiple signaling pathways to treat OP. Additionally, this also benefits us in further understanding the mechanism of the jintiange capsule for treating OP. [ABSTRACT FROM AUTHOR]

Recently, circular RNAs have been shown to function as critical regulators of many human cancers. However, the circRNA mechanism in laryngeal squamous cell carcinoma (LSCC) remains elusive. Recent investigations using bioinformatics analysis revealed high expression of hsa_circ_0023305 in LSCC tissues compared to normal tissues. Furthermore, we discovered that hsa_circ_0023305 expression level was positively correlated to tumor/node/metastasis (TNM) stage as well as lymph node metastasis in LSCC. Moreover, higher hsa_circ_0023305 levels were correlated to poorer LSCC patient outcomes. Knockdown of hsa_circ_0023305 significantly inhibited LSCC cell proliferation, invasion, and migration abilities. Our team validated that hsa_circ_0023305 functioned as a miR-218-5p sponge from a mechanistic perspective, targeting the melastatin-related transient receptor potential 7 (TRPM7) in LSCC cells. TRPM7 regulates a nonselective cation channel and promotes cancer proliferation and metastasis. Our data demonstrated that miR-218-5p was downregulated in LSCC and that miR-218-5p upregulation repressed LSCC proliferation and invasion both in vivo and in vitro. Additionally, we found that hsa_circ_0023305-mediated upregulation of TRPM7 inhibited miR-218-5p and contributed to LSCC migration, proliferation, and invasion. In summary, these data propose a new mechanism by which the hsa_circ_0023305/miR-218-5p/TRPM7 network enhances LSCC progression. [ABSTRACT FROM AUTHOR]

Larix olgensis is one of the main coniferous tree species in northeastern China and has excellent timber properties and strong tolerance to stress. Thirteen HD-Zip family genes with a complete CDS region were identified on the basis of cambium transcriptome data from Larix olgensis. All 13 genes were analyzed via bioinformatics by their conserved domain protein sequence and amino acid composition, including their physicochemical properties and protein structure. The spatiotemporal expression and abiotic stress responses of these genes were analyzed by real-time quantitative PCR. The results showed that the 13 HD-Zip genes of Larix olgensis were expressed in the roots, stems, and leaves at different stages. The expression of three of these genes (LoHDZ2, LoHDZ11, LoHDZ13) was highest in nonlignified roots, indicating that they might be related to the secondary growth of Larix olgensis; in addition, three genes (LoHDZ5, LoHDZ9, LoHDZ10) were highly expressed in partially and completely lignified stems and leaves. These 13 genes were expressed specifically under drought stress. The expression of two of them (LoHDZ1, LoHDZ5) was obviously upregulated, and the expression of 6 genes (LoHDZ2, LoHDZ3, LoHDZ4, LoHDZ8, LoHDZ10, LoHDZ13) was significantly downregulated. The expression trends indicate that these genes could be involved in drought stress. The expression of all 13 genes was downregulated when the plants were treated with 0.2 M NaCl for 96 h, indicating that these genes are inhibited by salt stress. Overall, the results have significant implications for the study of the gene function of members of the LoHD-Zip transcription factor family. [ABSTRACT FROM AUTHOR]

Italy is the first western country suffering heavy severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission and disease impact after coronavirus disease‐2019 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS‐CoV‐2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three nonsynonymous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bioinformatics tools. Amino acid analysis and changes in three‐dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favor virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation. Highlights: ‐two highly prevalent mutation have been developed by SARS‐CoV‐2, one on the Spike glycoprotein and one on the Nucleocapsid protein‐The enhanced torsional ability of Spike protein could favor virus binding to human cell receptors‐mutations on the Nucleocapsid region could influence the modulation of a number of virus properties, including cell signaling‐the study of SARS‐CoV‐2 mutations could be important for vaccines developmen [ABSTRACT FROM AUTHOR]

Pomacea canaliculata, known as an invasive freshwater snail, is also called a golden apple snail; its survival and expansion are greatly affected by temperature. In this study, high-throughput sequencing (RNA-seq) was used to perform comparative transcriptome analysis on the muscular tissue (G_M) of snails in Guangdong and Hunan. Differential gene screening was performed with FDR <0.05 and |log2FoldChange| >1 as the threshold, and a total of 1,368 differential genes were obtained (671 genes showed upregulation in snails from Guangdong, and 697 genes displayed upregulation in snails from Hunan). Fifteen genes were identified as candidate genes for the cold hardiness of Pomacea canaliculata. Among them, three genes were involved in energy metabolism (glycogen synthase, 1; DGK, 1; G6PD, 1); seven genes were involved in homeostasis regulation (HSP70, 2; BIP, 1; GPX, 1; GSTO 1, G6PD, 1; caspase-9, 1); two genes were involved in amino acid metabolism (glutamine synthetase, 1; PDK, 1); and four genes were involved in membrane metabolism (inositol-3-phosphate synthase, 1; Na+/K+-ATPase, 1; calcium-binding protein, 2). This study presents the molecular mechanisms for the cold hardiness of Pomacea canaliculata, which could provide a scientific basis for the forecast and prevention of harm from Pomacea canaliculata. [ABSTRACT FROM AUTHOR]

Compound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment. [ABSTRACT FROM AUTHOR]

Purpose. To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. Material and Methods. A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function. Results. The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of WFS1 p.C505S and CRYGD p.P24T changed markedly and may contribute significantly to iris coloboma and congenital cataract, respectively. Conclusions. We report a novel mutation, WFS1 p.C505S, and a known mutation, CRYGD p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of WFS1 p.C505S with iris coloboma has been demonstrated, although CRYGD p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract. [ABSTRACT FROM AUTHOR]

An accurate and efficient Large-for-Gestational-Age (LGA) classification system is developed to classify a fetus as LGA or non-LGA, which has the potential to assist paediatricians and experts in establishing a state-of-the-art LGA prognosis process. The performance of the proposed scheme is validated by using LGA dataset collected from the National Pre-Pregnancy and Examination Program of China (2010–2013). A master feature vector is created to establish primarily data pre-processing, which includes a features' discretization process and the entertainment of missing values and data imbalance issues. A principal feature vector is formed using GridSearch-based Recursive Feature Elimination with Cross-Validation (RFECV) + Information Gain (IG) feature selection scheme followed by stacking to select, rank, and extract significant features from the LGA dataset. Based on the proposed scheme, different features subset are identified and provided to four different machine learning (ML) classifiers. The proposed GridSearch-based RFECV+IG feature selection scheme with stacking using SVM (linear kernel) best suits the said classification process followed by SVM (RBF kernel) and LR classifiers. The Decision Tree (DT) classifier is not suggested because of its low performance. The highest prediction precision, recall, accuracy, Area Under the Curve (AUC), specificity, and F1 scores of 0.92, 0.87, 0.92, 0.95, 0.95, and 0.89 are achieved with SVM (linear kernel) classifier using top ten principal features subset, which is, in fact higher than the baselines methods. Moreover, almost every classification scheme best performed with ten principal feature subsets. Therefore, the proposed scheme has the potential to establish an efficient LGA prognosis process using gestational parameters, which can assist paediatricians and experts to improve the health of a newborn using computer aided-diagnostic system. [ABSTRACT FROM AUTHOR]

The bamboo snout beetle Cyrtotrachelus buqueti is a widely distributed wood-boring pest found in China, and its larvae cause significant economic losses because this beetle targets a wide range of host plants. A potential pest management measure of this beetle involves regulating olfactory chemoreceptors. In the process of olfactory recognition, pheromone-binding proteins (PBPs) play an important role. Homology modeling and molecular docking were conducted in this study for the interaction between CbuqPBP1 and dibutyl phthalate to better understand the relationship between PBP structures and their ligands. Site-directed mutagenesis and binding experiments were combined to identify the binding sites of CbuqPBP1 and to explore its ligand-binding mechanism. The 3D structural model of CbuqPBP1 has six a-helices. Five of these a-helices adopt an antiparallel arrangement to form an internal ligand-binding pocket. When docking dibutyl phthalate within the active site of CbuqPBP1, a CH-π interaction between the benzene ring of dibutyl phthalate and Phe69 was observed, and a weak hydrogen bond formed between the ester carbonyl oxygen and His53. Thus, Phe69 and His53 are predicted to be important residues of CbuqPBP1 involved in ligand recognition. Site-directed mutagenesis and fluorescence assays with a His53Ala CbuqPBP1 mutant showed no affinity toward ligands. Mutation of Phe69 only affected binding of CbuqPBP1 to cedar camphor. Thus, His53 (Between α2 and α3) of CbuqPBP1 appears to be a key binding site residue, and Phe69 (Located at α3) is a very important binding site for particular ligand interactions. [ABSTRACT FROM AUTHOR]

Objectives: To identify the molecular basis of Papillon–Lefèvre syndrome in two Chinese families. Methods: Peripheral blood and mouth swab samples were obtained, from which genomic DNA and RNA were isolated. Sanger sequencing was employed to identify the mutations. mRNA expression was tested by real‐time quantitative PCR. Evolutionary conservation, pathogenicity prediction and impact of protein structures of the mutations were conducted with bioinformatics tools and homology modelling. HEK293 cells were transfected with plasmids expressing wild‐type or mutated CTSC. CTSC protein expression level and enzyme activity were explored. Results: Mutation analysis revealed two novel compound heterozygous mutations, the c.190‐191insA and c.1211‐1212delA in patient 1 and the c.716A>G and c.757+1G>A in patient 2. In both patients, the levels of CTSC mRNA were significantly lower than in their relatives. Homology modelling analysis predicted that the mutations affect the structure and stability of the protein, and in vitro study showed that the CTSC proteins containing the mutations c.190‐191insA and c.1211‐1212delA, which result in truncated versions of protein, display impaired enzyme activity. The protein containing c.716A>G mutation showed quite similar enzyme activity compared to wild‐type CTSC. Conclusion: Our data support the molecular mechanism of PLS and enlarge the scope of CTSC gene mutations related to PLS. [ABSTRACT FROM AUTHOR]

Populus tomentosa, of section Populus, is distributed mainly in northern China. This species has high resistance to many diseases and insects, and it plays key roles in shelterbelts and urban afforestation in northern China. It has long been suspected to be a hybrid, but its parents remain unknown. In the present study, we report four newly sequenced complete cp genomes from section Populus and comparative genomic analyses of these new sequences and three published cp genome sequences. The seven cp genomes ranged from 155,853 bp (P. tremula var. davidiana) to 156,746 bp (P. adenopoda) in length, and their gene orders, gene numbers and GC contents were similar. We analyzed SNPs, indels, SSRs and repeats among the seven cp genomes, and eight small inversions were detected in the ndhC-trnV, rbcL-accD, petA-psbJ, trnW-trnP, rpl16-rps3, trnL-ycf15, ycf15-trnL, and ndhF-trnL intergenic regions. Furthermore, seven divergent regions (trnH-psbA, matK, psbM-psbD, ndhC-trnV, ycf1, ndhF-ccsA and ccsA-ndhD) were found in more highly variable regions. The phylogenetic tree reveals that P. tomentosa is closely related to P. alba and P. alba var. pyramidalis. Hence, P. alba was involved in the formation of P. tomentosa. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) is well recognized as one of the major threats to children's health globally. The increasing complexity of the etiology of HFMD still challenges disease control in China. There is little surveillance of the molecular epidemiological characteristics of the enteroviruses (EVs) that cause HFMD in Neijiang city or the Sichuan Basin area in Southwest China. In this study, demographic and epidemiological information for 14,928 probable HFMD cases was extracted and analyzed to describe the epidemic features of HFMD in Neijiang city from Jan 2010 to Dec 2017. The swab samples of select probable HFMD cases from 2012 to 2017 were tested by reverse transcription (RT) real-time PCR to identify the serotype distribution of EVs, and 110 randomly selected RT-real-time PCR positive samples were then amplified and analyzed for the VP1 or VP4 regions of EVs to further analyze the phylogenetic characteristics of the circulating strains in this area. The eight-year average annual incidence was 49.82 per 100,000 in Neijiang. The incidence rates varied between 19.51 and 70.73 per 100,000, demonstrating peaks of incidence in even-number years (2012, 2014 and 2016). The median age of the probable cases was 27 months and the interquartile range (25th to 75th percentile) of ages for the probable HFMD cases was between 14 and 42 months. The male-to-female ratio of the probable HFMD cases was 1.47:1, and scattered children were the major population classification (81.7%). Two epidemic peaks were observed: one major peak between April and July and the other lesser peak between October and December. Of 6513 probable cases tested with RT-real-time PCR, 4015 (61.6%) were positive for enterovirus with the serotype distribution as follows: EV71+, 30.1% (n = 1210); CV-A16+, 28.7% (n = 1154) and a sole pan-enterovirus+, 41.1% (n = 1651). A total of 91 cases (82.7%, 91/110) were successfully amplified and underwent phylogenetic analysis: all EV71+ cases were C4a serotype (n = 23/30); all CV-A16+ cases were B2b serotype (n = 24/30); of 42 sole pan-enterovirus+ samples, 20 were CV-A6, 14 were CV-A10 and the rest within this group were CV-A4 (n = 4), CV-A8 (n = 2), CV-A9 (n = 1) and CV-B3 (n = 1). Our findings provide important evidence that aids the improvement of strategies for vaccination against HFMD and comprehensive disease control in China. [ABSTRACT FROM AUTHOR]

Background: Enterocytozoon bieneusi is the most common microsporidian species causing diarrhea and other intestinal disorders in humans and animals. Like other infectious diseases, microsporidiosis usually disproportionately affects poor populations. In China, some ethnic minority areas remain poor. Currently, no information of E. bieneusi infection is available in minority populations. The present aims were to understand occurrence and genetic characterizations of E. bieneusi in ethnic minority groups from a poverty-stricken ethnic township in Yunnan Province, and to assess risk factors for E. bieneusi infection. Methodology/Principal findings: 289 fecal specimens were collected from Yao people (one specimen each) with and without diarrhea, in Yunnan Province. E. bieneusi was identified and genotyped by PCR and sequence analysis of the ITS region of the rRNA gene. An average prevalence of 8.30% (24/289) was observed and four genotypes were identified—genotype Peru6 (n = 21) and three novel genotypes (one each). Genotype Peru6 was detected in two family members in each of three families. In a phylogenetic analysis, all of four genotypes fell into group 1 with zoonotic potential. The people owning individual pit toilets had a statistically higher prevalence of E. bieneusi (16.67%, 12/72) than those using public pit toilets (6.06%, 12/198). Conclusions/Significance: This is the first report on occurrence and genetic characteristics of E. bieneusi in ethnic minority groups in China. Genotype Peru6 was found in humans in China for the first time and showed dominance in Yao people. The same genotype was found in some family members and all the genotypes fell into group 1, suggesting the possibility of anthroponotic and zoonotic transmissions. The majority (83.33%, 20/24) of E. bieneusi positive individuals did not present diarrhea. In any case, it is important to recognize their existence and the importance that asymptomatic individuals to E. bieneusi may have from an epidemiological point of view, as transmitters of this pathogen. The analysis of risk factors provides scientific evidence for the development of effective strategies for prevention and control of E. bieneusi infection. [ABSTRACT FROM AUTHOR]

Objective: To investigate a novel gene mutation in a Chinese patient with non‐syndromic hypodontia. Subjects and Methods: Mutation analysis was carried out by whole exome sequencing. Bioinformatics tools were used for the biophysical predictions of the mutative protein. Luciferase reporter assay was performed to analyse the effects of mutation on protein function. PAX9 and BMP4 gene expression from mutant cells was detected by qRT‐PCR. Results: A novel heterozygous mutation (c.G1057A) was detected in the patient but was not found in the controls. The novel missense mutation led to a Val111Met substitution in the paired box domain which was completely conserved evolutionarily, as analysed by dbNSFP. The mutation was predicted to be disease‐causing and harmful using MutationTaster and CADD, respectively. Protean of Lasergene showed that this mutation may lead to β‐region shortening in the mutant protein compared to the wild type. Luciferase reporter assay indicated that the mutated protein reduced the transactivation activity of PAX9. This mutation led to increased levels of PAX9 transcript and reduced levels of BMP4 transcript, likely due to compensatory activation and lower transactivation activity of mutant PAX9. Conclusion: This novel mutation (c.G1057A) in PAX9 caused hypodontia by altering PAX9 gene function and downregulating BMP4 gene expression. [ABSTRACT FROM AUTHOR]

The oriental river prawn, Macrobrachium nipponense, is an important commercial aquaculture resource in China. In order to overwinter, M. nipponense displays decreased physiological activity and less consumption of energy. Sudden warming would trigger molting and cause an extensive death, resulting in huge economic losses. Therefore, it is of great practical significance to study the molting mechanism of oriental river prawns. Molt-inhibiting hormone gene (MIH) plays a major role in regulating molting in crustaceans. In this study, a full length MIH cDNA of M. nipponense (Mn-MIH) was cloned from the eyestalk. The total length of the Mn-MIH was 925 bp, encoding a protein of 119 amino acids. Tissue distribution analysis showed that Mn-MIH was highly expressed in the eyestalk, and that it had relatively low expression in gill, ovary, and abdominal ganglion. Mn-MIH was detected in all developmental stages, and changed regularly in line with the molting cycle of the embryo and larva. Mn-MIH varied in response to the molting cycle, suggesting that Mn-MIH negatively regulates ecdysteroidogenesis. Mn-MIH inhibition by RNAi resulted in a significant acceleration of molting cycles in both males and females, confirming the inhibitory role of MIH in molting. After long-term RNAi males, but not females had significant weight gain, confirming that Mn-MIH plays an important role in growth of M. nipponense. Our work contributes to a better understanding of the role of Mn-MIH in crustacean molting and growth. [ABSTRACT FROM AUTHOR]

Flowering Chinese cabbage is one of the most important vegetable crops in southern China. Genetic improvement of various agronomic traits in this crop is underway to meet high market demand in the region, but the progress is hampered by limited number of molecular markers available in this crop. This study aimed to develop EST-SSR markers from transcriptome sequences generated by next-generation sequencing. RNA-seq of eight cabbage samples identified 48,975 unigenes. Of these unigenes, 23,267 were annotated in 56 gene ontology (GO) categories, 6,033 were mapped to 131 KEGG pathways, and 7,825 were assigned to clusters of orthologous groups (COGs). From the unigenes, 8,165 EST-SSR loci were identified and 98.57% of them were 1–3 nucleotide repeats with 14.32%, 41.08% and 43.17% of mono-, di- and tri-nucleotide repeats, respectively. Fifty-eight types of motifs were identified with , , , , and the most abundant. The lengths of repeated nucleotide sequences in all SSR loci ranged from 12 to 60 bp, with most (88.51%) under 20 bp. Among 170 primer pairs were randomly selected from a total of 4,912 SSR primers we designed, 48 yielded unambiguously polymorphic bands with high reproducibility. Cluster analysis using 48 SSRs classified 34 flowering Chinese cabbage cultivars into three groups. A large number of EST-SSR markers identified in this study will facilitate marker-assisted selection in the breeding programs of flowering Chinese cabbage. [ABSTRACT FROM AUTHOR]

Background: Barth syndrome (BTHS) is a rare X-linked recessive disease characterized by cardiomyopathy, neutropenia, skeletal myopathy and growth delay. Early diagnosis and appropriate treatment may improve the prognosis of this disease. The purpose of this study is to determine the role of targeted next-generation sequencing (NGS) in the early diagnosis of BTHS in children with cardiomyopathy.Methods: During the period between 2012 and 2015, a gene panel-based NGS approach was used to search for potentially disease-causing genetic variants in all patients referred to our institution with a clinical diagnosis of primary cardiomyopathy. NGS was performed using the Illumina sequencing system.Results: A total of 180 Chinese pediatric patients (114 males and 66 females) diagnosed with primary cardiomyopathy were enrolled in this study. TAZ mutations were identified in four of the male index patients, including two novel mutations (c.527A > G, p.H176R and c.134_136delinsCC, p.H45PfsX38). All four probands and two additional affected male family members were born at full term with a median birth weight of 2350 g (range, 2000-2850 g). The median age at diagnosis of cardiomyopathy was 3.0 months (range, 1.0-20.0 months). The baseline echocardiography revealed prominent dilation and trabeculations of the left ventricle with impaired systolic function in the six patients, four of which fulfilled the diagnostic criteria of left ventricular noncompaction. Other aspects of their clinical presentations included hypotonia (6/6), growth delay (6/6), neutropenia (3/6) and 3-methylglutaconic aciduria (4/5). Five patients died at a median age of 7.5 months (range, 7.0-12.0 months). The cause of death was heart failure associated with infection in three patients and cardiac arrhythmia in two patients. The remaining one patient survived beyond infancy but had fallen into a persistent vegetative state after suffering from cardiac arrest.Conclusions: This is the first report of systematic mutation screening of TAZ in a large cohort of pediatric patients with primary cardiomyopathy using the NGS approach. TAZ mutations were found in 4/114 (3.5%) male patients with primary cardiomyopathy. Our findings indicate that the inclusion of TAZ gene testing in cardiomyopathy genetic testing panels may contribute to the early diagnosis of BTHS. [ABSTRACT FROM AUTHOR]

To investigate the biodiversity of Trichoderma (Hypocreaceae) and their relation to sediment physical and chemical properties, we collected a total of 491 sediment samples from coastal wetlands (tidal flat and wetland) in Southeast China. Further, we applied two types of molecular approaches such as culture dependent and independent methods for identification of Trichoderma spp. A total of 254 isolates were obtained and identified to 13 species such as T. aureoviride, T. asperellum, T. harzianum, T. atroviride, T. koningiopsis, T. longibrachiatum, T. koningii. T. tawa, T. viridescens, T. virens, T. hamatum, T. viride, and T. velutinum by the culture-dependent (CD) method of these, T. tawa was newly described in China. Subsequently, the culture indepented method of 454 pyrosequencing analysis revealed a total of six species such as T. citrinoviride, T. virens, T. polysporum, T. harzianum/Hypocrea lixii and two unknown species. Notably, T. citrinoviride and T. polysporum were not found by the CD method. Therefore, this work revealed that the combination of these two methods could show the higher biodiversity of Trichoderma spp., than either of this method alone. Among the sampling sites, Hangzhou, Zhejiang Province, exhibited rich biodiversity and low in Fengxian. Correlation and Redundancy discriminant analysis (RDA) revealed that sediment properties of temperature, redox potential (Eh) and pH significantly influenced the biodiversity of Trichoderma spp. [ABSTRACT FROM AUTHOR]

Background: The invasion of plant by viruses cause major damage to plants and reduces crop yield and integrity. Devastating plant virus infection has been experienced at different times all over the world, which are attributed to different events of mutation, re-assortment and recombination occurring in the viruses. Strategies for proper virus management has been mostly limited to eradicating the vectors that spreads the plant viruses. However, development of prompt and effective diagnostic methods are required to monitor emerging and re-emerging diseases that may be symptomatic or asymptomatic in the plant as well as the genetic variation and evolution in the plant viruses. A survey of plant viruses infecting field-grown Tobacco crop was conducted in Anhui Province of China by the deep sequencing of sRNAs. Methods: Survey of plant viruses infecting Tobacco was carried based on 104 samples collected across the province. Nine different sRNA libraries was prepared and custom-made bioinformatics pipeline coupled with molecular techniques was developed to sequence, assemble and analyze the siRNAs for plant virus discovery. We also carried out phylogenetic and recombination analysis of the identified viruses. Results: Twenty two isolates from eight different virus species including Cucumber mosaic virus, Potato virus Y, Tobacco mosaic virus, Tobacco vein banding Mosaic virus, Pepper mottle virus, Brassica yellow virus, Chilli venial mottle virus, Broad bean wilt virus 2 were identified in tobacco across the survey area. The near-complete genome sequence of the 22 new isolates were determined and analyzed. The isolates were grouped together with known strains in the phylogenetic tree. Molecular variation in the isolates indicated the conserved coding regions have majorly a nucleotide sequence identity of 80-94 % with previously identified isolates. Various events of recombination were discovered among some of the isolates indicating that two or more viruses or different isolates of one virus infect the same host cell. Conclusion: This study describes the discovery of a consortium of plant viruses infecting Tobacco that are broadly distributed in Anhui province of China. It also demonstrates the effectiveness of NGS in identifying plant viruses without a prior knowledge of the virus and the genetic diversity that enhanced mixed infection. [ABSTRACT FROM AUTHOR]

Background Few genetic markers useful for the screening of lung cancer risk exist. Although related research has shown that certain expression profiles of micro ribonucleic acids ( miRNAs) are different in lung cancer versus the normal lung, such as miR-29a and miR-29s, the precise molecular mechanism of lung cancer remains obscure. In order to get a better understanding of the pathogenetic mechanism of lung cancer, we analyzed the differentially expressed genes ( DEGs) and identified featured miRNAs in lung cancer tissues. Methods We used the gene expression profile GSE10072, including 49 gene chips of non-tumor tissues and 58 gene chips of lung tumor specimens. The DEGs between these two groups were identified by Limma package in R language. The Tar Base database was used to construct the networks of miRNA regulating DEGs related to lung cancer. After ordering miRNAs regulating DEGs, we further screened featured miRNAs combined with the mi R2Disease database. Results A total of 5572 DEGs were obtained between lung cancer and control specimens. After constructing a miRNA regulatory network, a total of 398 regulations between 57 miRNAs and 321 target genes existed. By intergrating the mi R2Disease database and using a sorting algorithm, a total of six featured miRNAs related to lung cancer were identified, including miR-520h, miR-133a, miR-34, miR-103, miR-370, and miR-148. They might be involved in lung cancer progression by regulating ABCG2, PKM2, VAMP2, GPD1, MAP3K8, and DNMT3B, respectively. Conclusion The top 10 significant miRNAs, such as miR-520h, miR-133a, miR-34, and miR-103 may be potential therapeutic targets for lung cancer. [ABSTRACT FROM AUTHOR]

An epigenetic mechanism has been suggested to explain the effects of the maternal diet on the development of disease in offspring. The present study aimed to observe the effects of a maternal high-lipid, high-energy (HLE) diet on the DNA methylation pattern of male offspring in mice. Female C57BL/6J mice were fed an HLE diet during gestation and lactation. The genomic DNA methylations at promoter sites of genes in the liver, mRNA and protein levels of selected genes related to lipid and glucose metabolism were measured by microarray, real-time PCR and Western blot. The results indicated that the percentage of methylated DNA in offspring from dams that were fed an HLE diet was significantly higher than that from dams that were fed a chow diet, and most of these genes were hypermethylated in promoter regions. The nuclear protein content and mRNA levels of hypermethylated genes, such as PPARγ and liver X receptor α (LXRα), were decreased significantly in offspring in the HLE group. The results suggested that the DNA methylation profile in adult offspring livers was changed by the maternal HLE diet during gestation and lactation. [ABSTRACT FROM PUBLISHER]

Background: RH1 is one of the most clinically important blood group antigens in the field of transfusion and in the prevention of fetal incompatibility. The molecular analysis and characterization of serologic weak D phenotypes is essential to ensuring transfusion safety.Methods: Blood samples from a northeastern Chinese population were randomly screened for a serologic weak D phenotype. The nucleotide sequences of all 10 exons, adjacent flanking intronic regions, and partial 5' and 3' untranslated regions (UTRs) were detected for RHD genes. Predicted deleterious structural changes in missense mutations of serologicl weak D phenotypes were analyzed using SIFT, PROVEAN and PolyPhen2 software. The protein structure of serologic weak D phenotypes was predicted using Swiss-PdbViewer 4.0.1.Results: A serologic weak D phenotype was found in 45 individuals (0.03%) among 132,479 blood donors. Seventeen distinct RHD mutation alleles were detected, with 11 weak D, four partial D and two DEL alleles. Further analyses resulted in the identification of two novel alleles (RHD weak D 1102A and 399C). The prediction of a three-dimensional structure showed that the protein conformation was disrupted in 16 serologic weak D phenotypes.Conclusions: Two novel and 15 rare RHD alleles were identified. Weak D type 15, DVI Type 3, and RHD1227A were the most prevalent D variant alleles in a northeastern Chinese population. Although the frequencies of the D variant alleles presented herein were low, their phenotypic and genotypic descriptions add to the repertoire of reported RHD alleles. Bioinformatics analysis on RhD protein can give us more interpretation of missense variants of RHD gene. [ABSTRACT FROM AUTHOR]