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Gastroesophageal reflux related chronic cough (GERC), is a common type of chronic cough. Drug treatment is the first choice. But some patients are tired of taking medicine everyday and some patients can not benefit from drugs. For these patients, fundoplication may be the most effective method. However, the importance of fundoplication in treating GERC is undervalued, and there is very few meta-analysis looking into the effect and safety of fundoplication in treating GERC. To solve this question, we performed this meta-analysis. The PRISMA strategy was used for this study. Our study was registered with PROSPERO (ID: CRD42021251072). We searched PubMed, Medline, Web of Science, and the Cochrane databases from 1990 to December of 2022. The meta-analysis was performed with Review Manager 5.4 and Stata 14. After selection and exclusion, 15 articles out of 672 were included. The meta-analysis showed that the cure rate of laparoscopic fundoplication in treating GERC was 58% (95%CI: 52%–65%), with I2 = 45%; and the effective rate was 86% (95%CI: 80%–93%), with I2 = 0%. Laparoscopic fundoplication is effective for the most of GERC patients; however, when the goal is to cure GERC completely, a relatively conservative attitude should be taken. In terms of safety, laparoscopic fundoplication is quite reliable offered by skilled surgeons.

With the promotion and development of clean energy, it is challenging to ensure the optimization of control performance in frequency control of the hydropower-photovoltaic hybrid microgrid system caused by the output power fluctuation of photovoltaic power generation. In this study, an optimal load frequency controller (LFC) for a hydropower-photovoltaic hybrid microgrid system was designed to improve the dynamic response when the load and photovoltaic output power are perturbed based on the off-policy integral reinforcement learning algorithm. First, a mechanism model of the hydropower-photovoltaic hybrid microgrid system was established. Next, the LFC problem was transformed into a zero-sum game control problem based on the characteristics of the power system. Subsequently, three neural networks were employed to approximate the Nash equilibrium solution of the zero-sum game with historical input and output data when the system dynamics are completely unknown. Finally, simulation experiments were conducted to verify the effectiveness and optimality of the proposed method. The introduction of this method provides a new perspective for frequency control for the hydropower-photovoltaic hybrid microgrid system.

Abstract Background Tremendous research efforts have been made in the Alzheimer’s disease (AD) field to understand the disease etiology, progression and discover treatments for AD. Many mechanistic hypotheses, therapeutic targets and treatment strategies have been proposed in the last few decades. Reviewing previous work and staying current on this ever-growing body of AD publications is an essential yet difficult task for AD researchers. Methods In this study, we designed and implemented a natural language processing (NLP) pipeline to extract gene-specific neurodegenerative disease (ND) -focused information from the PubMed database. The collected publication information was filtered and cleaned to construct AD-related gene-specific publication profiles. Six categories of AD-related information are extracted from the processed publication data: publication trend by year, dementia type occurrence, brain region occurrence, mouse model information, keywords occurrence, and co-occurring genes. A user-friendly web portal is then developed using Django framework to provide gene query functions and data visualizations for the generalized and summarized publication information. Results By implementing the NLP pipeline, we extracted gene-specific ND-related publication information from the abstracts of the publications in the PubMed database. The results are summarized and visualized through an interactive web query portal. Multiple visualization windows display the ND publication trends, mouse models used, dementia types, involved brain regions, keywords to major AD-related biological processes, and co-occurring genes. Direct links to PubMed sites are provided for all recorded publications on the query result page of the web portal. Conclusion The resulting portal is a valuable tool and data source for quick querying and displaying AD publications tailored to users’ interested research areas and gene targets, which is especially convenient for users without informatic mining skills. Our study will not only keep AD field researchers updated with the progress of AD research, assist them in conducting preliminary examinations efficiently, but also offers additional support for hypothesis generation and validation which will contribute significantly to the communication, dissemination, and progress of AD research.

Background: Asthma and cardio-cerebrovascular diseases (CVDs) share a common etiology of chronic systemic inflammation. Our manuscript was to investigate the association between childhood asthma and CVDs in middle-aged and elderly. Methods: A total of 12,070 US middle-aged and elder were enrolled in the National Health and Nutrition Examination Survey. Childhood asthma was defined as a previous diagnosis of asthma at

BackgroundMandibular tumor surgery necessitates precise osteotomies based on tumor boundaries; however, conventional osteotomies often lack accuracy in predicting osteotomy positions and planes, potentially leading to excessive resection of normal bone tissues or residual tumors, thus compromising postoperative quality of life and clinical outcomes. Robotic-assisted surgery (RAS) augmented with artificial intelligence (AI) offers precise localization capabilities, aiding surgeons in achieving accurate osteotomy positioning. This study aimed to evaluate the feasibility and accuracy of a robotic magnetic navigation system for positioning and osteotomy in an intraoral surgical trial of a mandibular tumor model.MethodsPatient computed tomography (CT) imaging data of mandibular chin and body tumors were utilized to create 3D printed models, serving as study subjects for mandibular tumor resection. Ten pairs of models were printed for the experimental and control groups. The experimental group (EG) underwent osteotomy using a robot-assisted surgical navigation system, performing osteotomy under robotic navigation following alignment based on preoperative design. The control group (CG) underwent traditional surgery, estimating osteotomy position empirically according to preoperative design. Postoperative CT scans were conducted on both models, and actual postoperative results were compared to preoperative design. Osteotomy accuracy was evaluated by positional and angular errors between preoperatively designed and actual osteotomy planes.ResultsFor ten randomly selected spots on the left and right sides, respectively, the EG group had mean distance errors of 0.338 mm and 0.941 mm. These values were obtained from the EG group. In the EG group, on the left side, the mean angular errors were 14.741 degrees, while on the right side, they were 13.021 degrees. For the 10 randomly selected spots on the left and right sides, respectively, the CG had mean distance errors of 1.776 mm and 2.320 mm. This is in contrast to the results obtained by the EG. It was determined that the left side had a mean angle error of 16.841 degrees, while the right side had an error of 18.416 degrees in the CG group. The above results indicated significantly lower point errors of bilateral osteotomy planes in the experimental group compared to the control group.ConclusionThis study demonstrates the feasibility of electromagnetic navigation robot-assisted intraoral osteotomy for mandibular tumors and suggests that this approach can enhance the precision of clinical surgery.

Abstract CRISPR-mediated knock-in (KI) technology opens a new era of fluorescent-protein labeling in zebrafish, a preferred model organism for in vivo imaging. We described here an optimized zebrafish gene-tagging strategy, which enables easy and high-efficiency KI, ensures high odds of obtaining seamless KI germlines and is suitable for wide applications. Plasmid donors for 3′-labeling were optimized by shortening the microhomologous arms and by reducing the number and reversing the sequence of the consensus Cas9/sgRNA binding sites. To allow for scar-less KI across the genome, linearized dsDNA donors with 5′-chemical modifications were generated and successfully incorporated into our method. To refine the germline screen workflow and expedite the screen process, we combined fluorescence enrichment and caudal-fin junction-PCR. Furthermore, to trace proteins expressed at a low abundance, we developed a fluorescent signal amplifier using the transcriptional activation strategy. Together, our strategies enable efficient gene-tagging and sensitive expression detection for almost every gene in zebrafish.

Background: The treatment of patellar tendon injury has always been an unsolved problem, and mechanical characterization is very important for its repair and reconstruction. Elastin is a contributor to mechanics, but it is not clear how it affects the elasticity, viscoelastic properties, and structure of patellar tendon.Methods: The patellar tendons from six fresh adult experimental pigs were used in this study and they were made into 77 samples. The patellar tendon was specifically degraded by elastase, and the regional mechanical response and structural changes were investigated by: (1) Based on the previous study of elastase treatment conditions, the biochemical quantification of collagen, glycosaminoglycan and total protein was carried out; (2) The patellar tendon was divided into the proximal, central, and distal regions, and then the axial tensile test and stress relaxation test were performed before and after phosphate-buffered saline (PBS) or elastase treatment; (3) The dynamic constitutive model was established by the obtained mechanical data; (4) The structural relationship between elastin and collagen fibers was analyzed by two-photon microscopy and histology.Results: There was no statistical difference in mechanics between patellar tendon regions. Compared with those before elastase treatment, the low tensile modulus decreased by 75%–80%, the high tensile modulus decreased by 38%–47%, and the transition strain was prolonged after treatment. For viscoelastic behavior, the stress relaxation increased, the initial slope increased by 55%, the saturation slope increased by 44%, and the transition time increased by 25% after enzyme treatment. Elastin degradation made the collagen fibers of patellar tendon become disordered and looser, and the fiber wavelength increased significantly.Conclusion: The results of this study show that elastin plays an important role in the mechanical properties and fiber structure stability of patellar tendon, which supplements the structure-function relationship information of patellar tendon. The established constitutive model is of great significance to the prediction, repair and replacement of patellar tendon injury. In addition, human patellar tendon has a higher elastin content, so the results of this study can provide supporting information on the natural properties of tendon elastin degradation and guide the development of artificial patellar tendon biomaterials.

This paper examines how Australian residential load profiles may evolve in the short to medium term future. These profiles can be used to support simulation studies of the future Australian network within an environment that is transitioning to renewable energy and broader use of electricity as a tool for decarbonisation. The daily profiles rely heavily on the Australian Energy Market Operator (AEMO) forecasts for future annual energy usage. The period from 2024 to 2050 will be transformational. In the residential networks, two secular trends are particularly important in expanding residential generation and electrification. New daily load profiles have been constructed using historical Australian profiles and adding additional components for solar generation, battery operation and electrification activities. The entire aggregated residential network is expected to have reverse midday power flow on any average day from 2024 onwards due to the rapid increase in electric vehicle (EV) usage. The domestic energy demand forecasting methodology presented in this work related to Australia can easily be adopted to carry out similar forecasting for any country of the world.

Abstract Background Obstructive sleep apnea (OSA) is one of the leading respiratory disorders, increasing the risk of cardiometabolic diseases. In the study, we investigated the association between OSA and the risk of cardiometabolic diseases and all‐cause and cardiovascular mortality in adults. Methods Participants were enrolled in the National Health and Nutrition Examination Survey. The baseline covariates were compared between participants with and without OSA status. Multivariable logistic regression was performed to explore the association between OSA and cardiometabolic diseases, while Cox proportional regression was performed for all‐cause and cardiovascular mortality. Results OSA status was positively associated with higher risks of cardiometabolic diseases, including hypertension (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.14–1.45; p

Restricted mouth opening (trismus) is one of the most common complications following head and neck cancer treatment. Early initiation of mouth-opening exercises is crucial for preventing or minimizing trismus. Current methods for these exercises predominantly involve finger exercises and traditional mouth-opening training devices. Our research group successfully designed an intelligent mouth-opening training device (IMOTD) that addresses the limitations of traditional home training methods, including the inability to quantify mouth-opening exercises, a lack of guided training resulting in temporomandibular joint injuries, and poor training continuity leading to poor training effect. For this device, an interactive remote guidance mode is introduced to address these concerns. The device was designed with a focus on the safety and effectiveness of medical devices. The accuracy of the training data was verified through piezoelectric sensor calibration. Through mechanical analysis, the stress points of the structure were identified, and finite element analysis of the connecting rod and the occlusal plate connection structure was conducted to ensure the safety of the device. The findings support the effectiveness of the intelligent device in rehabilitation through preclinical experiments when compared with conventional mouth-opening training methods. This intelligent device facilitates the quantification and visualization of mouth-opening training indicators, ensuring both the comfort and safety of the training process. Additionally, it enables remote supervision and guidance for patient training, thereby enhancing patient compliance and ultimately ensuring the effectiveness of mouth-opening exercises.

Cancer cells frequently exhibit aberrant redox homeostasis and adaptation to oxidative stress. Hence abrogation of redox adaptation in cancer cells can be exploited for therapeutic benefit. Here we report SGK3 functions as an anti-oxidative factor to promote cell growth and drug resistance in cervical cancers harboring PIK3CA helical domain mutations. Mechanistically, SGK3 is activated upon oxidative stress and exerts anti-ROS activity by stabilizing and activating the antioxidant enzyme catalase. SGK3 interacts with and phosphorylates catalase, promoting its tetrameric state and activity. Meanwhile, SGK3 phosphorylates GSK3β and protects catalase from GSK3β-β-TrCP mediated ubiquitination and proteasomal degradation. Furthermore, SGK3 inhibition not only potentiates CDK4/6 inhibitor Palbociclib-mediated cytotoxicity, but also overcomes cisplatin resistance through ROS-mediated mechanisms. These data uncover the role of SGK3 in maintaining redox homeostasis and suggest that the SGK3-catalase antioxidant signaling axis may be therapeutically targeted to improve treatment efficacy for cervical cancers carrying PIK3CA helical domain mutations.

Background: Oxidative stress and inflammatory responses are critical factors in calcium oxalate (CaOx) crystal-induced renal injury. Reactive oxygen species (ROS) are usually produced in the cytoplasm and mitochondria and trigger the priming and activation of the NLRP3 inflammasome, thereby regulating cytokines and inflammation. Polydatin is a plant rhizome extract with anti-inflammatory, antioxidant, and antitumor effects. However, it remains not clear whether and how these pathophysiological processes exists in CaOx crystal-induced renal inflammatory injury. Methods: Here, we measured the expression of the NLRP3 inflammasome, IL-18, IL-1β, intracellular and mitochondrial ROS (mtROS) levels and relevant morphological changes in treated renal tubular epithelial cells (TECs) and stone-forming rats. The study further explored the action of intracellular ROS and mtROS on these inflammatory damage, and the beneficial effects and pathway of polydatin. Results: We verified that CaOx crystal-induced cytoplasmic ROS and mtROS upregulation promoted the priming and activation of the NLRP3 inflammasome, thereby stimulating IL-18/1β maturation and activation. Polydatin can relieve oxidative stress and inflammatory damage by decreasing ROS. We further demonstrated that mtROS is the main target for polydatin to exert the NLRP3 inflammasome-regulating function. The inhibition of mtROS can effectively relieve the inflammatory damage to TECs and kidney caused by CaOx crystal. Conclusion: These findings provide new insight into the relationship between mitochondrial damage and inflammation in nephrolithiasis and show that polydatin-mediated anti-inflammatory and antioxidative protection is a therapeutic strategy for, but not limited to, crystalline nephropathy.

Background Low vitamin D status has been linked to an increased risk for various inflammatory diseases. Conflicting results have been reported regarding chronic obstructive pulmonary disease (COPD). This study aims to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentrations with COPD risk and survival.Methods We included 403 648 participants with serum 25(OH)D measurements and free of COPD at baseline from UK Biobank. Follow-up was until 30 September 2021. Multivariable-adjusted cox regression models were applied to estimate HRs and 95% CIs for the associations of season-standardised 25(OH)D concentrations with COPD risk and survival. The restricted cubic splines were used to assess dose–response relationship. Kaplan-Meier estimation was used to create graphs of the survival curves.Results During a median follow-up of 12.3 (IQR: 11.4–13.2) years, 11 008 cases of COPD were recorded. We observed a non-linear inverse association between 25(OH)D concentrations and COPD risk. Compared with participants in the fourth quintile of 25(OH)D, those in the lowest quintile were associated with a 23% higher risk (HR, 1.23; 95% CI, 1.16 to 1.31). Stronger associations were observed for the risk in men and current smokers (Both p for interaction

Gastric cancer poses a societal and economic burden, prompting an exploration into the development of materials suitable for gastric reconstruction. However, there is a dearth of studies on the mechanical properties of porcine and human stomachs. Therefore, this study was conducted to elucidate their mechanical properties, focusing on interspecies correlations. Stress relaxation and tensile tests assessed the hyperelastic and viscoelastic characteristics of porcine and human stomachs. The thickness, stress–strain curve, elastic modulus, and stress relaxation were assessed. Porcine stomachs were significantly thicker than human stomachs. The stiffness contrast between porcine and human stomachs was evident. Porcine stomachs demonstrated varying elastic modulus values, with the highest in the longitudinal mucosa layer of the corpus and the lowest in the longitudinal intact layer of the fundus. In human stomachs, the elastic modulus of the longitudinal muscular layer of the antrum was the highest, whereas that of the circumferential muscularis layer of the corpus was the lowest. The degree of stress relaxation was higher in human stomachs than in porcine stomachs. This study comprehensively elucidated the differences between porcine and human stomachs attributable to variations across different regions and tissue layers, providing essential biomechanical support for subsequent studies in this field.

Background: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth.Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) were conducted to explore the underlying mechanisms of DLL3-related in the development and prognosis of COAD. On the basis of DLL3-related signature genes, a prognostic model and a nomogram were constructed. Finally, CIBERSORT was applied to assess the proportion of immune cell types in COAD sample.Results: Survival analysis showed a significant difference in overall survival between high- and low-expression group (p = 0.0092), with COAD patients in the high-group having poorer 5-year survival rate. Gene functional enrichment analysis revealed that DLL3-related DEGs were mainly enriched in tumor- and immunity-related signaling pathways, containing AMPK pathway and mitophagy-animal. The comparison of COAD tumor and normal, DLL3 high- and low-expression groups by GSEA found that AMPK signaling pathway and mitophagy-animal were inhibited. Nomogram constructed from DLL3-related signature genes had a good predictive effect on the prognosis of COAD. We found the highest correlation between DLL3 and interstitial dendritic cell (iDC), natural killer (NK) cell and Interstitial dendritic cell (Tem). DLL3 was also revealed to be diagnostic for COAD. In clinical sample, we identified higher DLL3 expression in colon cancer tissue than in adjacent control (p < 0.0001) and in metastasis than in primary lesion (p = 0.0056). DLL3 expression was associated with stage and high DLL3 expression was observed to predict poorer overall survival (p = 0.004).Conclusion: It suggested that DLL3 may offer prognostic value and therapeutic potential for individualized treatment of COAD, and that it may has a diagnostic role in COAD.

ObjectiveThis study was designed to assess ferroptosis regulator gene (FRG) expression patterns in patients with TNBC based on data derived from The Cancer Genome Atlas (TCGA). Further, it was utilized to establish a TNBC FRG signature, after which the association between this signature and the tumor immune microenvironment (TIME) composition was assessed, and relevant prognostic factors were explored.MethodsThe TCGA database was used to obtain RNA expression datasets and clinical information about 190 TNBC patients, after which a prognostic TNBC-related FRG signature was established using a least absolute shrinkage and selection operator (LASSO) Cox regression approach. These results were validated with separate data from the Gene Expression Omnibus (GEO). The TNBC-specific prognostic gene was identified via this method. The STEAP3 was then validated through Western immunoblotting, immunohistochemical staining, and quantitative real‐time polymerase chain reaction (RT-qPCR) analyses of clinical tissue samples and TNBC cell lines. Chemotherapy interactions and predicted drug sensitivity studies were investigated to learn more about the potential clinical relevance of these observations.ResultsThese data revealed that 87 FRGs were differentially expressed when comparing TNBC tumors and healthy tissue samples (87/259, 33.59%). Seven of these genes (CA9, CISD1, STEAP3, HMOX1, DUSP1, TAZ, HBA1) are significantly related to the overall survival of TNBC patients. Kaplan-Meier analyses and established FRG signatures and nomograms identified CISD1 and STEAP3 genes of prognostic relevance. Prognostic Risk Score values were positively correlated with the infiltration of CD4+ T cells (p = 0.001) and myeloid dendritic cells (p =0.004). Further evidence showed that STEAP3 was strongly and specifically associated with TNBC patient OS (P

BackgroundRecent studies indicated that Ginseng potentiate cancer treatments. Ginseng-based carbon dots (GCDs) might possess properties to kill cancer cells and inhibit malignant tumor development and invasion. This study aimed to prepare GCDs, examine their effects on cancer cell growth and invasion, and explore the mechanisms involved.MethodsGCDs were synthesized, purified, and characterized. Cells were cultured with GCDs and were tested for growth, invasiveness, and wound healing. RNA was extracted for transcriptomics analysis. Protein expression was evaluated using western blot and immunohistochemistry. Mice were injected with cancer cells and treated with PBS or GCDs. Tumor volume was evaluated.ResultsGCDs were successfully synthesized and purified. The solution was yellow under sunlight and fluorescent blue under ultraviolet light. Electron microscopy showed GCDs with a uniform shape without apparent aggregation and an average diameter of about 4 nm. GCDs inhibited Cal-27, SCC-25, and SCC-7 cancer cell growth at concentrations of >250-300 μg/mL, while GCDs inhibited the non-cancerous HaCaT cells at concentrations >400 μg/mL. Immunofluorescence showed that GCDs could enter the cells. Transcriptomics revealed 552 downregulated mRNAs and 338 upregulated ones, including mRNAs involved in the oxidative phosphorylation and ferroptosis pathways. GCDs induced the ferroptosis of cancer cells, as shown by decreased GPX-4 and increased COX-2. GCDs decreased cell invasion and migration. In vivo, GCDs decreased tumor growth without apparent organ toxicity and promoted CD4+ T cell infiltration in the tumor.ConclusionGCDs appear to possess anticancer properties by increasing ferroptosis, resulting in cancer cell growth inhibition in vitro and in vivo.

Peppers (Capsicum annuum L.), as a horticultural crop with one of the highest ascorbic acid contents, are negatively affected by detrimental environmental conditions both in terms of quality and productivity. In peppers, the high level of ascorbic acid is not only a nutrient substance but also plays a role in environmental stress, i.e., drought stress. When suffering from drought stress, plants accumulate dehydrins, which play important roles in the stress response. Here, we isolated an SK3-type DHN gene CaDHN2 from peppers. CaDHN2 was located in the nucleus, cytoplasm, and cell membrane. In CaDHN2-silenced peppers, which are generated by virus-induced gene silencing (VIGS), the survival rate is much lower, the electrolytic leakage is higher, and the accumulation of reactive oxygen species (ROS) is greater when compared with the control under drought stress. Moreover, when CaDHN2 (CaDHN2-OE) is overexpressed in Arabidopsis, theoverexpressing plants show enhanced drought tolerance, increased antioxidant enzyme activities, and lower ROS content. Based on yeast two-hybrid (Y2H), GST-pull down, and bimolecular fluorescence complementation (BiFC) results, we found that CaDHN2 interacts with CaGGP1, the key enzyme in ascorbic acid (AsA) synthesis, in the cytoplasm. Accordingly, the level of ascorbic acid is highly reduced in CaDHN2-silenced peppers, indicating that CaDHN2 interacts with CaGGP1 to affect the synthesis of ascorbic acid under drought stress, thus improving the drought tolerance of peppers. Our research provides a basis for further study of the function of DHN genes.

The outbreak of milky disease of Chinese mitten crab caused by M. bicuspidata seriously restricted the development of the crab industry. In this study, the mitochondrial genome sequence of M. bicuspidata was assembled, annotated, and further analyzed. The results indicated that the complete mitochondrial genome of M. bicuspidata was 75,095 bp, which contained two rRNAs, 23 tRNAs, and 13 protein-coding genes. The phylogenetic tree of 13 yeasts based on the complete mitochondrial genome was constructed which showed that M. bicuspidata (accession number OK514652) and M. bicuspidata (accession number MW147605.1) were clustered in a clade. To sum up, our research results would further provide essential data for the systematics and evolution study of M. bicuspidata.

Abstract Background We conducted a study to explore the relationship between pathological cytomorphologic features and the percentage of anaplastic lymphoma kinase (ALK)-positive cells to better predict pulmonary adenocarcinoma prognosis with crizotinib treatment. Patients and methods We investigated 60 cases of patients with ALK-positive advanced or metastatic non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to screen for ALK rearrangement. Fluorescence in situ hybridization (FISH) was used to detect the percentage of ALK-positive cells. The primary objectives of the study were the progression-free survival (PFS), the 3-year overall survival, and the 3-year overall survival (OS) rates. The secondary objectives of the study were the disease control rate (DCR) and the overall response rate (ORR). Results We compared the pathological cytomorphologic features of 60 cases of ALK-positive pulmonary adenocarcinoma, of which 21 cases were ALK-positive with signet ring cell cytomorphologic characteristics. There were statistical differences in the ORR (p = 0.019), DCR (p = 0.032), and PFS (p = 0.047) between the signet ring cell group and group without signet ring cells. Of these, 37 cases were ALK-positive with EML4 (echinoderm microtubule associated protein like 4)-ALK high percentage of positivity group. These cases benefited more from crizotinib treatment in the ORR (p = 0.046) and achieved a longer PFS (p = 0.036) compared to those with EML4-ALK low percentage of positivity group. Conclusions Signet ring cell cytomorphologic characteristics of pulmonary adenocarcinoma are associated with the percentage of ALK-positive cells. Signet ring cell cytomorphologic characteristics and the percentage of ALK-positive cells might predict the prognosis of pulmonary adenocarcinoma with crizotinib treatment. Trial registration The study was approved by the Institutional Review Board (Medical Ethics Committee of Yantai Yuhuangding Hospital). The registration number is NO.2016[193].

The number of egg-laying is an important indicator of reproduction performance in poultry breeding. To investigate the relationship between the function of Angiotensin-converting enzyme (ACE) and egg-laying performance of Taihang chicken, the mRNA and protein expression and single nucleotide polymorphism (SNP) of ACE were detected. Analysis of ACE bioinformatics and association analysis of polymorphisms were then performed. The polymorphisms analysis of ACE showed that three SNP loci (g.5066812A>C, g.5080076G>A, and g.5072728A>G) were detected in 800 Taihang chickens with egg-laying records. Association analysis of egg-laying found that ACE g.5066812A>C mutation was significantly associated with the egg-laying performance of Taihang chickens (P < 0.05), and the individuals with the g.5066812A>C mutation showed significantly increasing egg-laying. The mRNA expression was significantly higher in individuals with the AA genotype mutation than those with the AC and CC genotypes (P < 0.01), and the expression of ACE protein levels was consistent with the mRNA expression. Bioinformatics analysis indicated that these mutations affected the secondary and tertiary structure of ACE. This study provides new insights into ACE affecting chicken egg production and some basis for improving the egg production rate of Taihang chickens.

Abstract Background Cigarette smoking and PM2.5 are important risk factors of Chronic Obstructive Pulmonary Disease (COPD). However, the joint association of cigarette smoking and PM2.5 with COPD is unknown. Methods A community-based study was conducted among urban and rural adults aged 40 + years between May and December of 2015 in Jiangsu Province, China. The outcome variable was spirometry-defined COPD. Explanatory measures were smoking status (non-smokers or smokers) and PM2.5 exposure [low level (

Abstract Background Circular RNAs (circRNAs) is a newly discovered type of non-coding RNA, the abnormal expression of which has been demonstrated in many types of human tumors. So they have been considered as promising candidates as diagnostic and therapeutic targets in cancer. This research aimed to screen the profile of circRNA expression in salivary adenoid cystic carcinoma (SACC). Methods Using the threshold of FDR 2 or

The growth and development of skeletal muscle is a physiological process regulated by a variety of genes and signaling pathways. As a posttranscriptional regulatory factor, circRNA plays a certain regulatory role in the development of animal skeletal muscle in the form of a miRNA sponge. However, the role of circRNAs in muscle development and growth in goats is still unclear. In our study, apparent differences in muscle fibers in Wu'an goats of different ages was firstly detected by hematoxylin-eosin (HE) staining, the circRNA expression profiles of longissimus dorsi muscles from 1-month-old (mon1) and 9-month-old (mon9) goats were screened by RNA-seq and verified by RT–qPCR. The host genes of differentially expressed (DE) circRNAs were predicted, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG) of host genes with DE circRNAs were performed to explore the functions of circRNAs. The circRNA-miRNA-mRNA networks were then constructed using Cytoscape software. Ten significantly differentially expressed circRNAs were also verified in the mon1 and mon9 groups by RT–qPCR. Luciferase Reporter Assay was used to verify the binding site between circRNA and its targeted miRNA. The results showed that a total of 686 DE circRNAs were identified between the mon9 and mon1 groups, of which 357 were upregulated and 329 were downregulated. Subsequently, the 467 host genes of DE circRNAs were predicted using Find_circ and CIRI software. The circRNA-miRNA-mRNA network contained 201 circRNAs, 85 miRNAs, and 581 mRNAs; the host mRNAs were associated with “muscle fiber development” and “AMPK signaling pathway” and were enriched in the FoxO signaling pathway. Competing endogenous RNA (ceRNA) network analysis showed that novel_circ_0005314, novel_circ_0005319, novel_circ_0009256, novel_circ_0009845, novel_circ_0005934 and novel_circ_0000134 may play important roles in skeletal muscle growth and development between the mon9 and mon1 groups. Luciferase Reporter Assay confirmed the combination between novel_circ_0005319 and chi-miR-199a-5p, novel_circ_0005934 and chi-miR-450-3p and novel_circ_0000134 and chi-miR-655. Our results provide specific information related to goat muscle development and a reference for the goat circRNA profile.

Background: Verbascoside (VB), as an active component of multiple medicinal plants, has been proved to exert anti-oxidative, anti-aging and neuroprotective effects. This study was designed to investigate whether VB could play a cardioprotective role in septic heart injury. Methods: Mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to induce sepsis. The treatment group received an intraperitoneally injection of VB (20 mg/kg) before LPS challenge. Transthoracic echocardiography, ELISA, immunofluorescence, and qPCR were performed to assess the effect of VB on heart function, oxidative stress, inflammation and apoptosis. Transmission electronic microscopy and immunoblotting were used to evaluate the mitochondrial morphology and biogenesis of the septic heart. In vitro experiments were also performed to repeat above-mentioned assays. Results: Compared with LPS group, the VB treatment group showed improved cardiac function in sepsis. VB alleviated oxidative stress and inflammatory cell infiltration, as well as cardiomyocyte apoptosis. Specifically, VB could restore sepsis-induced mitochondrial alterations via regulating mitochondrial biogenesis. These results were also confirmed in in vitro experiments. Conclusion: Verbascoside could protected from sepsis-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and apoptosis, as well as promoting mitochondrial biogenesis.

Abstract Background Colon cancer is one of the leading causes of cancer deaths in the USA and around the world. Molecular level characters, such as gene expression levels and mutations, may provide profound information for precision treatment apart from pathological indicators. Transcription factors function as critical regulators in all aspects of cell life, but transcription factors-based biomarkers for colon cancer prognosis were still rare and necessary. Methods We implemented an innovative process to select the transcription factors variables and evaluate the prognostic prediction power by combining the Cox PH model with the random forest algorithm. We picked five top-ranked transcription factors and built a prediction model by using Cox PH regression. Using Kaplan-Meier analysis, we validated our predictive model on four independent publicly available datasets (GSE39582, GSE17536, GSE37892, and GSE17537) from the GEO database, consisting of 925 colon cancer patients. Results A five-transcription-factors based predictive model for colon cancer prognosis has been developed by using TCGA colon cancer patient data. Five transcription factors identified for the predictive model is HOXC9, ZNF556, HEYL, HOXC4 and HOXC6. The prediction power of the model is validated with four GEO datasets consisting of 1584 patient samples. Kaplan-Meier curve and log-rank tests were conducted on both training and validation datasets, the difference of overall survival time between predicted low and high-risk groups can be clearly observed. Gene set enrichment analysis was performed to further investigate the difference between low and high-risk groups in the gene pathway level. The biological meaning was interpreted. Overall, our results prove our prediction model has a strong prediction power on colon cancer prognosis. Conclusions Transcription factors can be used to construct colon cancer prognostic signatures with strong prediction power. The variable selection process used in this study has the potential to be implemented in the prognostic signature discovery of other cancer types. Our five TF-based predictive model would help with understanding the hidden relationship between colon cancer patient survival and transcription factor activities. It will also provide more insights into the precision treatment of colon cancer patients from a genomic information perspective.

Abstract Purpose Squamous cell carcinomas and adenocarcinomas are the most common types of cervical cancer. Compared to squamous cell carcinomas, adenocarcinomas are more common in younger women and have a poorer prognosis. Yet, so far, no useful biomarkers have been developed for these two types of cancer. In the following study, we examined the combination of cytokeratin 5/6, p63, p40 and MUC5AC for distinguishing squamous cell carcinoma (SCC) from adenocarcinoma of the cervix (AEC). Materials and methods A total of 101 SCC and 108 AEC were collected. Immunohistochemical analyses were conducted to determine the expression of CK5/6, p63, p40, CK7 and MUC5AC. One pathologist who was blinded to the patient’s clinical and pathological data interpreted the staining results. Results MUC5AC and CK7 were detected in 81.48 and 82.41% of AEC cases compared to 9.9 and 49.50% of SCC cases (P

Abstract Background While several multigene signatures are available for predicting breast cancer prognosis, particularly in early stage disease, effective molecular indicators are needed, especially for triple-negative carcinomas, to improve treatments and predict diagnostic outcomes. The objective of this study was to identify transcriptional regulatory networks to better understand mechanisms giving rise to breast cancer development and to incorporate this information into a model for predicting clinical outcomes. Methods Gene expression profiles from 1097 breast cancer patients were retrieved from The Cancer Genome Atlas (TCGA). Breast cancer-specific transcription regulatory information was identified by considering the binding site information from ENCODE and the top co-expressed targets in TCGA using a nonlinear approach. We then used this information to predict breast cancer patient survival outcome. Result We built a multiple regulator-based prediction model for breast cancer. This model was validated in more than 5000 breast cancer patients from the Gene Expression Omnibus (GEO) databases. We demonstrated our regulator model was significantly associated with clinical stage and that cell cycle and DNA replication related pathways were significantly enriched in high regulator risk patients. Conclusion Our findings demonstrate that transcriptional regulator activities can predict patient survival. This finding provides additional biological insights into the mechanisms of breast cancer progression.

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells’ cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100 % specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.

The Yunnan province of China is a typical humid region but with several severe region-wide droughts. Drought indices are generally used to identify and characterize drought events, and then play a key role in drought prediction. Therefore, a novel prediction model was proposed to predict a comprehensive drought indicator (meteorological composite index, MCI) in Yunnan province. This model combined the recurrent neural networks (RNN) based on a gated recurrent neural unit (GRU) and convolutional neural networks (CNN) with optimization using the modified particle swarm optimization (PSO) algorithm. In this model, pre-processed predictor data were input into the GRU module to extract the time features of the sequences. Furthermore, the feature matrices were input into the CNN module to extract the deep local features and the inter-relationship of the predictors. The model was trained and used to predict the monthly MCI drought index of the representative five stations of Yunnan province from 1960 to 2020. The combined model was evaluated by comparison with traditional machine learning models such as the least absolute shrinkage and selection operator (LASSO) and random forest (RF), and the traditional GRU model. The results show significantly improved skills in root mean square error, mean absolute error and Nash–Sutcliffe efficiency coefficient. This novel method was valuable for the monthly drought prediction in Yunnan province and related climate-risk management.

LncRNAs are essential for regulating skeletal muscle. However, the expression profile and function of lncRNAs in goat muscle remains unclear. Here, an average of ~14.58 Gb high-quality reads were obtained from longissimus dorsi tissues of 1-month-old (n = 3) and 9-month-old (n = 3) Wu’an black goats using RNA sequencing. Of a total of 3441 lncRNAs, 1281 were lincRNAs, 805 were antisense lncRNAs, and 1355 were sense_overlapping lncRNAs. These lncRNAs shared some properties with goats, such as fewer exons, shorter transcript, and open reading frames (ORFs) length. Among them, 36 differentially expressed lncRNAs (DE lncRNA) were identified, and then 10 random lncRNAs were validated by RT-qPCR. Furthermore, 30 DE lncRNAs were neighboring 71 mRNAs and several genes were functionally enriched in muscle development-related pathways, such as APC, IFRD1, NKX2-5, and others. Additionally, 36 DE lncRNAs and 2684 mRNAs were included in co-expression interactions. A lncRNA-miRNA-mRNA network containing 4 lncRNAs, 3 miRNAs, and 8 mRNAs was finally constructed, of which XR_001296113.2 might regulate PDLIM7 expression by interaction with chi-miR-1296 to affect skeletal muscle development. This study revealed the expression profile of goat lncRNAs for further investigative studies and provides a fuller understanding of skeletal muscle development.

Background Previous studies have documented a high incidence of toxicity in patients with ultra‐central non‐small cell lung cancer (UC‐NSCLC) treated with stereotactic body radiation therapy (SBRT). However, these studies mainly focused on early stage patients and included small sample populations. We reviewed the outcomes and toxicity of SBRT in patients with advanced stage UC‐NSCLC treated at our institution. Methods Fifty‐one consecutive patients with advanced UC‐NSCLC treated with SBRT using a regular regimen of 35 Gy administered in five fractions between December 2014 and August 2017 were reviewed. UC was defined as tumors abutting or overlapping the trachea or the proximal bronchial tree. We included locally advanced patients who were unfit or unwilling to receive conventional chemoradiotherapy and patients with metastatic or postoperative recurrent disease. Clinical outcomes, dosimetric parameters, and SBRT toxicity were analyzed. Results The median age was 63 years (range: 35–82), and the median tumor diameter was 6.8 cm (range: 2.1–12.4). The overall median follow‐up duration was 17 months (25.5 months for surviving patients). The median local control was 17 months for stage III patients and 11 months for stage IV or recurrent patients. Grade 3 or higher toxicity was observed in 9.8% of patients: G3 radiation pneumonitis (5.9%) and possible treatment‐related death (3.9%). Conclusion SBRT with a moderate dose in 4–6 fractions is effective and tolerable for patients with advanced stage UC‐NSCLC. However, caution should be taken considering possible treatment‐related death. Further studies are warranted.

The duodenum is an important digestive organ for poultry and houses a variety of microbes that help chickens to enhance nutrient absorption and improve production. To evaluate the characteristic of gut microbiome, duodenum content samples from 42-week-old native Taihang chickens with high (H) and low (L) egg-yielding were collected for 16S rRNA amplicon sequencing analysis. Consequently, 1,361,341 sequences were clustered into 2055 OTUs, with percentages of affiliation of 96.50 and 57.30% at phylum and genus levels. Firmicutes, Proteobacteria, Cyanobacteria and Bacteroidetes were the dominant phylum, with a lower ratio of Firmicutes/Bacteroidetes in H group than in L group (p < 0.05). At genus level, overrepresentation of Bacteroides, Faecalibacterim, and Enterococcus and underrepresentation of Romboutsia were found in H group. No significant difference in overall diversity of microbiota was observed between two groups. LEFSe analysis revealed Enterococcus was significantly enriched in H group. Importantly, Enterococcus and Lactobacillus were negatively correlated. Functional prediction analysis showed the proportion of microbiota involved in the metabolism process was the highest and enriched in H group. Differences in microbiota composition between the two groups, which may be related to intestinal function difference, also provide promising biomarkers for improving laying hen production.

Abstract Background Colorectal Cancer (CRC) is the third leading cause of cancer death among men and women in the United States. Research has shown that the risk of CRC associates with genetic and lifestyle factors. It is possible to prevent or minimize certain CRC risks by adopting a healthy lifestyle. Existing Clinical Decision Support Systems (CDSS) mainly targeted physicians as the CDSS users. As a result, the availability of patient-oriented CDSS is limited. Our project is to develop patient-oriented CDSS for active CRC management. Methods We implemented an online patient-oriented CRC CDSS for the public to learn about CRC, assess CRC risk levels, understand personalized CRC risk factors, and seek professional advices for people with CRC concerns. The system is implemented based on the Django Model-View-Controller (MVC) framework with an extensible background MySQL database. A CRC absolute risk prediction model is applied to calculate the personalized CRC risk score with a user-friendly web survey. An interactive dashboard using advanced data visualization technics will display and interpret the risk scores and factors. Based on the risk assessment, a structured decision tree algorithm will provide the recommendations on customized CRC screening methods. The CDSS also provides a search function for preferred providers and hospitals based on geographical information and patient preferences. Results A prototype of the patient-oriented CRC CDSS has been developed. It provides an open assessment of potential CRC risks via an online survey. The CRC risk predictive model has been implemented. The prediction outcomes of risk levels and factors are presented to the users through a personalized interactive visualization interface, to guide the public on how to reduce the CRC risks by changing their living styles (such as smoking and drinking) and diet characteristics (such as consumptions of red meat and milk). The CDSS will also provide customized recommendations on screening methods based on the corresponding risk factors. For users seeking professional clinicians, the CDSS also provides a convenient tool for searching nearby hospitals and available doctors based on the location preferences and providers characteristics (such as gender, language, and specialty). Conclusions This CRC CDSS prototype provides a patient-friendly interface for CRC risk assessment and gives a personalized interpretation on important CRC risk factors. It is a useful tool to educate the public on CRC, to provide guidance on minimizing CRC risks, and to promote early CRC screening that reduces the CRC occurrences.

Purpose. To report a technique for performing sutureless intrascleral fixation of a posterior chamber intraocular lens (PC-IOL) and analyzing the clinical outcomes and postoperative complications. Study Design. 68 eyes of 66 patients who received the technique were studied retrospectively. Methods. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber depth (ACD), IOL tilt and decentration, corneal topography (K1 and K2), and postoperative complications were determined at 3 months. Results. The mean preoperative BCVA was 1.63 ± 1.24 logMAR units, and the mean postoperative BCVA was 0.74 ± 0.59 logMAR units at 3 months (P

Objective. The primary aim of this investigation was to analyze the microbiome in patients with combined periodontal-endodontic lesions. Method. Patients with loose and/or painful teeth referred for treatment from March 2020 to December 2020 in the First People’s Hospital of Jinzhong were recruited. Samples were collected from teeth diagnosed as chronic periodontics (PE), ulcerative pulpitis (PU), and retrograde pulpitis (RE). Genomic DNA was extracted. The quantitative polymerase chain reaction, targeting the 16S ribosomal RNA (rRNA), was adopted for the quantification of bacteria. Then, the V3-V4 hypervariable regions of the 16S rRNA gene were amplified and subjected to next-generation sequencing. The statistical analysis was performed by R software (V3.5.1). Results. A total of 57 qualified samples were collected from 48 patients and analyzed (7 PE, 21 PU, and 19 RE). By linear discriminant analysis effect size, Kingella and Barnesiella were significantly increased in the periodontal pocket of retrograde pulpitis (RE-PE), compared with PE. The relative abundance of Clostridiales Incertae Sedis XI, Fusobacteriaceae, Fusobacterium, Parvimonas, Micrococcaceae, and Rothia was significantly increased in the pulp of retrograde pulpitis (RE-PU) than PU and RE-PE. Prevotella, Leptotrichia, Porphyromonas, Streptococcus, and Fusobacterium are consistently at a high abundance, across PU, RE-PE, and RE-PU. Conclusion. The current study highlighted the evidence that a specific microbial community is associated with the occurrence of retrograde pulpitis. The microenvironment of the root canal and pulp chamber will select microbiota. This study offered insights into the pathogenesis of retrograde pulpitis.

Introduction: P2X7R excitation-interrelated NLRP3 inflammasome activation induced by high glucose contributes to the pathogenesis of diabetic retinopathy (DR). Relaxin-3 is a bioactive peptide with a structure similar to insulin, which has been reported to be effective in diabetic cardiomyopathy models in vivo and in vitro. However, it is not known whether relaxin-3 has a beneficial impact on DR, and the underlying mechanisms of the effect are also remain unknown.Methods and Results: The retinas of male streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rats were characterized. Human retinal microvascular endothelial cells (HRMECs) were used to evaluate the anti-inflammatory, antiapoptotic, antipyroptotic and anti-migration effects of H3 relaxin by transmission electron microscopy, wound-healing assay, transwell assay, flow cytometry, cytokine assays and western-blot analysis. After H3 relaxin treatment, changes of the ultrastructure and expression of NLRP3 inflammasome related proteins in the retinas of rats were compared with those in the diabetic group. In vitro, H3 relaxin played a beneficial role that decreased cell inflammation, apoptosis, pyroptosis and migration stimulated by advanced glycation end products (AGEs). Moreover, inhibition of P2X7R and NLRP3 inflammasome activation decreased NLRP3 inflammasome-mediated injury that similar to the effects of H3 relaxin. H3 relaxin suppressed the stimulation of apoptosis, pyroptosis and migration of HRMECs in response to AGEs mediated by P2X7R activation of the NLRP3 inflammasome.Conclusion: Our findings provide new insights into the mechanisms of the inhibitory effect of H3 relaxin on AGE-induced retinal injury, including migration, apoptosis and pyroptosis, mediated by P2X7R-dependent activation of the NLRP3 inflammasome in HRMECs.

Background This study aimed to develop multi-RNA-based models using a competing endogenous RNA (ceRNA) regulatory network to provide survival risk prediction in head and neck squamous cell carcinoma (HNSCC). Methods All long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA expression data and clinicopathological features related to HNSCC were derived from The Cancer Genome Atlas. Differentially expressed RNAs were calculated using R. Prognostic factors were identified using univariate Cox regression analysis. Functional analysis was performed using GO, KEGG pathways, and PPI network. Based on the results, we derived a risk signature and compared high- and low-risk subgroups using LASSO regression analysis. Survival analysis and the relationship between risk signature and clinicopathological features were performed using log-rank tests and Cox regression analysis. A ceRNA regulatory network was constructed, and prognostic lncRNAs and miRNA expression levels were validated in vitro and in vivo. Results A list of 207 lncRNAs, 18 miRNAs and 362 mRNAs related to overall survival was established. Five lncRNAs (HOTTIP, LINC00460, RMST, SFTA1P, and TM4SF19-AS1), one miRNA (hsa-miR-206), and one mRNA (STC2) were used to construct the ceRNA network. Three prognostic models contained 13 lncRNAs, eight miRNAs, and 17 mRNAs, which correlated with the patient status, disease-free survival (DFS), stage, grade, T stage, N stage, TP53 mutation status, angiolymphatic invasion, HPV status, and extracapsular spread. KEGG pathway analysis revealed significant enrichment of “Transcriptional misregulation in cancer” and “Neuroactive ligand-receptor interaction.” In addition, HOTTIP, LINC00460, miR-206 and STC2 were validated in GTEx data, GEO microarrays and six HNSCC cell lines. Conclusions Our findings clarify the interaction of ceRNA regulatory networks and crucial clinicopathological features. These results show that prognostic biomarkers can be identified by constructing multi-RNA-based prognostic models, which can be used for survival risk prediction in patients with HNSCC.

AimsOxymatrine (OMT) has been identified to possess immunomodulatory, antiinflammatory and anticancer properties. This study aimed to investigate its precise function and the underlying molecular mechanisms in renal cell carcinoma progression.MethodsThe antineoplastic effect of oxymatrine was investigated by CCK-8 assay, cell cycle analysis, apoptosis assay, wound healing experiment, transwell assay, and drug-sensitivity analysis in renal cancer cells following oxymatrine treatment. The modulation of oxymatrine on β-catenin was analyzed through western blot and immunofluorescence assay. β-catenin overexpression was employed to determine the key role of β-catenin in oxymatrine-inhibited renal cell carcinoma in vitro. In addition, animal model was established to investigate the effect of oxymatrine on tumor growth in vivo.ResultsOxymatrine inhibited renal cell carcinoma progression in vitro, including cell proliferation, apoptosis, migration, invasion and chemotherapy sensitivity. Further mechanistic studies demonstrated that oxymatrine exerted its antineoplastic effect through suppressing the expression of β-catenin. Moreover, in nude mice model, oxymatrine exhibited remarkable inhibition of tumor growth, which was consistent with our in vitro results.ConclusionsOur findings illuminate oxymatrine as an effective antitumor agent in renal cell carcinoma, and suggest it a promising therapeutic application in renal cell carcinoma treatment.

Abstract Background Characterization of the microbial diversity and symbiont dynamics of ticks may help to understand the development of ticks and reveal new strategies to control tick-transmitted pathogens, which has not yet been explored in the Tibetan tick Haemaphysalis tibetensis. This tick species is widely distributed in the Tibetan Plateau, and is recognized as one of the primary parasites affecting domestic and wild animals. Methods In the present study, the endosymbionts of H. tibetensis were characterized using diagnostic polymerase chain reaction (diagnostic PCR), and further evaluated for tissue distribution and population dynamics at each developmental stage of ticks and in tissues at different reproductive statuses by real-time quantitative polymerase chain reaction (RT-qPCR). Results Two symbionts were found in H. tibetensis, and named as CLS-Ht (Coxiella-like symbiont in H. tibetensis) and RLS-Ht (Rickettsia-like symbiont in H. tibetensis). They showed 100% infection rate in both females and males of H. tibetensis. CLS-Ht and RLS-Ht can be observed within eggs, larvae, nymphs and adults, which indicates vertical transmission in H. tibetensis. CLS-Ht was specifically distributed in the female ovaries and Malpighian tubules, whereas RLS-Ht was detected within ovaries, Malpighian tubules, salivary glands and midguts of the ticks. Real-time qPCR suggested that adult ticks carried the largest amount of CLS-Ht and RLS-Ht with CLS-Ht having a significantly higher presence in females than in males (P

Neurogenin-2 (Ngn2) is a basic helix-loop-helix (bHLH) transcription factor that contributes to the identification and specification of neuronal fate during neurogenesis. In our previous study, we found that Ngn2 plays an important role in alleviating neuronal apoptosis, which may be viewed as an attractive candidate target for the treatment of cerebral ischemia. However, novel strategies require an understanding of the function and mechanism of Ngn2 in mature hippocampal neurons after global cerebral ischemic injury. Here, we found that the expression of Ngn2 decreased in the hippocampus after global cerebral ischemic injury in mice and in primary hippocampal neurons after oxygen glucose deprivation (OGD) injury. Then, transactivator of transcription (TAT)-Ngn2, which was constructed by fusing a TAT domain to Ngn2, was effectively transported and incorporated into hippocampal neurons after intraperitoneal (i.p.) injection and enhanced cognitive functional recovery in the acute stage after reperfusion. Furthermore, TAT-Ngn2 alleviated hippocampal neuronal damage and apoptosis, and inhibited the cytochrome C (CytC) leak from the mitochondria to the cytoplasm through regulating the expression levels of brain-derived neurotrophic factor (BDNF), phosphorylation tropomyosin-related kinase B (pTrkB), Bcl-2, Bax and cleaved caspase-3 after reperfusion injury in vivo and in vitro. These findings suggest that the downregulation of Ngn2 expression may have an important role in triggering brain injury after ischemic stroke and that the neuroprotection of TAT-Ngn2 against stroke might involve the modulation of BDNF-TrkB signaling that regulates caspase-dependent and mitochondrial apoptotic pathways, which may be an attractive therapeutic strategy for cerebral ischemic injury.

The end-use quality of wheat, including its unique rheology and viscoelastic properties, is predominantly determined by the composition and concentration of gluten proteins. While, the mechanism regulating expression of the seed storage protein (SSP) genes and other related genes in wheat remains unclear. In this study, we report on the cloning and functional identification of TaFUSCA3, a B3-superfamily transcription factor (TF) gene in wheat. Sequence alignment indicated that wheat and barley FUSCA3 genes are highly conserved. Quantitative reverse-transcription (qRT)-PCR analysis showed that the transcript of TaFUSCA3 was accumulated mostly in the stamens and the endosperms of immature wheat seeds. Yeast-one-hybrid results proved that the full-length TaFUSCA3 and its C-terminal region had transcriptional activities. Yeast-two-hybrid and bimolecular fluorescence complementation assays indicated that TaFUSCA3 could activate the expression of the high molecular weight glutenin subunit gene Glu-1Bx7 and interact with the seed-specific bZIP protein TaSPA. DNA-protein-interaction enzyme-linked immunosorbent assay demonstrated that TaFUSCA3 specifically recognizes the RY-box of the Glu-1Bx7 promoter region. Transient expression results showed that TaFUSCA3 could trans-activate the Glu-1Bx7 promoter, which contains eight RY-box sequences. TaFUSCA3 was unable to activate the downstream transcription when the RY-box was fully mutated. TaFUSCA3 could activate the transcription of the At2S3 gene promoter in a complementation of loss-of-function experiment using the Arabidopsis thaliana line fus3-3, which is a FUSCA3 mutant, demonstrating the evolutionary conservation of the TaFUSCA3 gene. In conclusion, the wheat B3-type TF, TaFUSCA3, is functional conserved between monocot and dicot, and could regulate SSP gene expression by interacting specifically with TaSPA.

In this paper, an Internet of Things (IoT) platform is proposed for Multi-Microgrid (MMG) system to improve unbalance compensation functionality employing three-phase four-leg (3P-4L) voltage source inverters (VSIs). The two level communication system connects the MMG system, implemented in Power System Computer Aided Design (PSCAD), to the cloud server. The local communication level utilizes Modbus Transmission Control Protocol/Internet Protocol (TCP/IP) and Message Queuing Telemetry Transport (MQTT) is used as the protocol for global communication level. A communication operation algorithm is developed to manage the communication operation under various communication failure scenarios. To test the communication system, it is implemented on an experimental testbed to investigate its functionality for MMG neutral current compensation (NCC). To compensate the neutral current in MMG, a dynamic NCC algorithm is proposed, which enables the MGs to further improve the NCC by sharing their data using the IoT platform. The performance of the control and communication system using dynamic NCC is compared with the fixed capacity NCC for unbalance compensation under different communication failure conditions. The impact of the communication system performance on the NCC sharing is the focus of this research. The results show that the proposed system provides better neutral current compensation and phase balancing in case of MMG operation by sharing the data effectively even if the communication system is failing partially.

Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS) characterized by nocturnal chronic intermittent hypoxia (CIH). The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation.Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD) group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks). Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG) injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats' GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group.CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.

Postmenopausal osteoporosis is a complicated and multi-factorial disease. To study the metabolic profiles and pathways activated in osteoporosis, Eight rats were oophorectomized (OVX group) to represent postmenopausal osteoporosis and the other eight rats were sham operated (Sham group) to be the control. The biochemical changes were assessed with metabolomics using a gas chromatography/time-of-flight mass spectrometry. Metabolomic profile using serial blood samples obtained prior to and at different time intervals after OVX were analyzed by principal component analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA). The conventional indicators (bone mineral density, serum Bone alkaline phosphatase (B-ALP) and N-telopeptide of type I collagen (NTx) of osteoporosis in rats were also determined simultaneously. In OVX group, the metabolomics method could describe the endogenous changes of the disease more sensitively and systematically than the conventional criteria during the progression of osteoporosis. Significant metabolomic difference was also observed between the OVX and Sham groups. The metabolomic analyses of rat plasma showed that levels of arachidonic acid, octadecadienoic acid, branched-chain amino acids (valine, leucine and isoleucine), homocysteine, hydroxyproline and ketone bodies (3-Hydroxybutyric Acid) significantly elevated, while levels of docosahexaenoic acid, dodecanoic acid and lysine significantly decreased in OVX group compared with those in the homeochronous Sham group. Considering such metabolites are closely related to the pathology of the postmenopausal osteoporosis, the results suggest that potential biomarkers for the early diagnosis or the pathogenesis of osteoporosis might be identified via metabolomic study.

In the big data era,the research institutes and enterprises manage massive scientific data of various disciplines,such as oceanography,meteorology,geology and petroleum,and service the clients with the analysis results that are treated as data products.Traditionally,these institutes do not provide the service-oriented production platform for data products.The shortages and challenges of the production process were analyzed,the new requirements of online production platform for scientific data product was proposed,the architecture of platform was designed,and key techniques including the serviceoriented interface for data analysis algorithms,mechanisms of data security and isolation,and the pricing model for data product were studied.Finally,the application of online production platform as a case study was explained.

The goal of distributed consensus is quite simple i.e.how to decide a value among a group of coordinated processes in the distributed environment.However,the problem is turned out to be very difficult while facing the different distributed environment.The even harder problem is that some consensus protocols are hard to be implemented in practical systems.Some results of distributed consensus algorithms under different distributed environment assumptions were reviewed.In addition,some practical systems based on consensus for achieving high reliability were discussed.