Search

Background: The SARS-CoV-2 non-Spike (S) structural protein targets on nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, are grossly overlooked in COVID vaccine development. The current Spike-only vaccines bear an intrinsic shortfall for promotion of a fuller T cell immunity. Vaccines designed to target conserved epitopes could elicit strong cellular immune responses that would synergize with B cell responses and lead to long-term vaccine success. We pursue a universal (pan-SARS-CoV-2) vaccine against Delta, Omicrons and ever-emergent new mutants. Methods and findings: We explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation (N = 1,478) of infection-free participants (aged 18–85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6–8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). This UB-612 booster vaccination is safe and well tolerated without SAEs. Conclusions: By targeting conserved epitopes on viral S2, M and N proteins, UB-612 could provide potent, broad and long-lasting B-cell and T-cell memory immunity and offers the potential as a universal vaccine to fend off Omicrons and new VoCs without resorting to Omicron-specific immunogens. Trial registration: ClinicalTrials.gov: NCT04773067; ClinicalTrials.gov ID: NCT05293665; ClinicalTrials.gov ID: NCT05541861. Author summary: The Omicron variant of SARS-CoV-2 has swept the globe with a rapid succession of dominating sublineages from BA.1, BA.2, to the current BA.5 with increasing infectivity and antibody evasion. Concerningly, the non-Spike structure proteins that promote T-cell immunity have been grossly overlooked in vaccine development. Looking beyond short-interval boosters and omicron-updated vaccines, a pragmatic approach to curbing ever-emergent new mutants would be "universal (pan-SARS-CoV-2) vaccines" as exemplified by UB-612, a multitope-vaccine armed with Spike (S1-RBD and S2) and non-Spike (Nucleocapsid N and Membrane M) targets, allowing booster vaccination to elicit broadly-recognizing and durable B-/T-cell memory immunity. Sequence-conserved Th/CTL epitope peptides were designed from S2, N and M proteins to synergistically enhance memory helper and cytotoxic T-cell immunity and RBD targeted B-cell immunity. [ABSTRACT FROM AUTHOR]

Introduction: The Michigan Hand Outcomes Questionnaire (MHQ) is a patient-reported outcome measure previously validated in patients with rheumatoid arthritis (RA) using classical test theory. Rasch analysis is a more rigorous method of questionnaire validation that has not been used to test the psychometric properties of the MHQ in patients with RA. The objective of this study is to evaluate the validity and reliability of the MHQ for measuring outcomes in patients with RA with metacarpophalangeal joint deformities. Methods: We performed a Rasch analysis using baseline data from the Silicone Arthroplasty in Rheumatoid Arthritis (SARA) prospective cohort study. All domains were tested for threshold ordering, item fit, targeting, differential-item functioning, unidimensionality, and internal consistency. Results: The Function and Work domains showed excellent fit to the Rasch model. After making adjustments, the Pain, Activities of Daily Living (ADL) and Satisfaction domains also fulfilled all Rasch model criteria. The Aesthetics domain met the majority of Rasch criteria, but could not be tested for unidimensionality. Conclusions: After collapsing disordered thresholds and removing misfitting items, the MHQ demonstrated reliability and validity for assessing outcomes in patients with RA with metacarpophalangeal joint deformities. These results suggest that interpreting individual domain scores may provide more insight into a patient's condition rather than analyzing an overall MHQ summary score. However, more Rasch analyses are needed in other RA populations before making adjustments to the MHQ. [ABSTRACT FROM AUTHOR]

Distracted driving is a leading cause of traffic accidents. It is influenced by driver attitude toward secondary tasks; however, field-based studies on the effects of low-perceived-risk tasks on lateral driving have rarely been reported. A total of 17 experienced non-professional drivers were recruited to participate in two secondary tasks: a cognitive experiment (conversation) and a visual distraction experiment (observation of following vehicles), each representing low-perceived-risk secondary tasks. One-way analysis of variance (ANOVA) was conducted to evaluate the effects of low-perceived-risk tasks on lateral driving performance. ANOVA results indicated that compared with baseline (no task) lateral performance, lane-keeping ability was enhanced during cognitive distractions. In the visual distraction experiment, more than 50% of the distractions required 1–2 s. Lane deviation and its growth rate increased with the duration of distraction. Compared with cognitive distraction, lane deviation increased significantly with visual distraction, and lane-keeping performance was seriously impaired. For low-perceived-risk tasks, visual distractions impaired driving safety more seriously, compared with cognitive distractions, suggesting that drivers misjudge the risks associated with visual tasks. These results can contribute to the design of advanced driving-assistance systems and improve professional driver programs, potentially reducing the frequency of traffic accidents caused by distracted driving. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the application of four autosomal kits and the sensitivity of the combined paternity index (CPI) cutoff value (CPI≥10000) in parentage testing. First, 1442 real trios and 803 real duos were tested using the Goldeneye 25A kit. The Goldeneye 25A kit covers the autosomal short tandem repeat (STR) loci of the other three kits, so we calculated the CPI value of every case for the four kits. Second, three complex close relative kinship cases were also analyzed to evaluate the application of the CPI cutoff value. The CPI values of all trio cases were higher than 10000 using the four kits; the CPI values of all duo cases were higher than 10000 using the Goldeneye 25A kit; and the CPI values of a portion of the duo cases were lower than 10000 using the other three kits. In the three complex close relative cases, the alleged father or mother was not excluded using 40 autosomal STRs. Adding X chromosome short tandem repeats (X-STR) and samples of biological fathers or mothers, the conclusions were confirmed. The four kits were adequate to draw conclusions in the trio cases; the Goldeneye 25A Kit was adequate to draw conclusions in the duo cases; and the other three kits were not sufficient for a portion of the duo cases. The CPI cutoff value was sensitive for real trio and duo cases. In complex close relative kinship cases, high CPI values may result in false conclusions. [ABSTRACT FROM AUTHOR]

Background: Arthroscopic repair of rotator cuff tears, although commonly performed, carries the risk of retears. Therefore, bioremediation techniques such as platelet-rich plasma injections have been used as adjuvant therapies. The clinical efficacy of platelet-rich plasma in the arthroscopic repair of full-thickness rotator cuff injury is controversial. We performed a meta-analysis to evaluate the clinical effectiveness and safety of platelet-rich plasma and provide evidence-based medical recommendations for selecting the proper clinical treatment plan for full-thickness rotator cuff injuries. Methods: A search for the terms “platelet-rich plasma” and “rotator cuff” was performed in the PubMed, EMBASE, and Cochrane Library databases using a computer. After conducting quality evaluations and data extraction, RevMan 5.3 software was used to combine the effect sizes, and the GRADEpro Guideline Development Tool was used to rate the level of evidence from aspects of functional score, pain score and retear rate. Results: Eight randomized controlled trials involving 566 patients were included. The long-term retear rate(RR = 0.96, 95% CI [0.52, 1.78], P = .89), Constant score(RR = 0.96, 95% CI [0.52, 1.78], P = .89), and Visual Analog Scale score for pain (SMD = -0.28, 95% CI [-0.60, 0.04], P = .08), as well as both the long-term and short-term Disabilities of the Arm, Shoulder, and Hand scores(SMD = -0.13, 95% CI [-0.44, 0.18], P = .41;SMD = -0.02, 95% CI [-0.40, 0.36], P = .93), were not significantly different between the platelet-rich plasma and control groups. However, the short-term retear rate(RR = 0.29, 95% CI [0.13, 0.65], P = .003) and Visual Analog Scale score (SMD = -0.41, 95% CI [-0.62, -0.19], P = .0002) were significantly lower, while the short-term Constant score(SMD = 0.37, 95% CI [0.19, 0.55], P < .0001) and short-term and long-term University of California at Los Angeles activity scores (SMD = 0.38, 95% CI [0.16, 0.60], P = .0008;SMD = 0.85, 95% CI [0.48, 1.22], P < .00001) were significantly higher, in the platelet-rich plasma group than in the control group. Conclusion: Platelet-rich plasma injection can effectively improve the short-term outcomes following arthroscopic repair of full-thickness rotator cuff tears, thus reducing the rate of retears, alleviating pain, and improving patients’ shoulder function. Specifically, the clinical outcomes are better with the use of platelet-rich plasma in single-row fixation than in other fixation techniques. Therefore, platelet-rich plasma injection can be recommended as an adjuvant therapy in single-row repair for improved short-term results. [ABSTRACT FROM AUTHOR]

The user-based collaborative filtering (CF) algorithm is one of the most popular approaches for making recommendation. Despite its success, the traditional user-based CF algorithm suffers one serious problem that it only measures the influence between two users based on their symmetric similarities calculated by their consumption histories. It means that, for a pair of users, the influences on each other are the same, which however may not be true. Intuitively, an expert may have an impact on a novice user but a novice user may not affect an expert at all. Besides, each user may possess a global importance factor that affects his/her influence to the remaining users. To this end, in this paper, we propose an asymmetric user influence model to measure the directed influence between two users and adopt the PageRank algorithm to calculate the global importance value of each user. And then the directed influence values and the global importance values are integrated to deduce the final influence values between two users. Finally, we use the final influence values to improve the performance of the traditional user-based CF algorithm. Extensive experiments have been conducted, the results of which have confirmed that both the asymmetric user influence model and global importance value play key roles in improving recommendation accuracy, and hence the proposed method significantly outperforms the existing recommendation algorithms, in particular the user-based CF algorithm on the datasets of high rating density. [ABSTRACT FROM AUTHOR]

Background: The awareness, treatment and control of diabetes mellitus (DM) can effectively reflect on the social status of diabetes conditions. Although several researchers have investigated the awareness, treatment and control rates of diabetes mellitus in China, little is known about their association with risk factors. This study aims to examine the relationship between risk factors and awareness, treatment and control of diabetes mellitus in northeast China. Methods: A cross-sectional survey was conducted in 2012. Multistage stratified random cluster sampling design was used to select participants aged 18 to 79 years old. The analysis was based on a representative sample of 1,854 adult subjects. Multivariable logistic regression analysis was used to examine socio-demographic factors associated with the levels of awareness, treatment and control of diabetes mellitus. Results: The awareness, treatment, and control rates of diabetes mellitus were 64.1%, 52.9% and 44.2%, respectively. In the multivariable logistic regression analysis, family history of diabetes was significantly positively associated with awareness (OR, 2.145; 95% CI, 1.600–2.875) and treatment (OR, 2.021; 95% CI, 1.559–2.619) of diabetes mellitus, while negatively associated with control (OR, 0.671; 95% CI, 0.529–0.951). Cigarette smokers and alcohol drinkers were less likely than non-smokers and non-drinkers to be aware of their blood glucose levels (OR, 0.895, 0.614; 95% CI, 0.659–1.216, 0.446–0.844, respectively). Participants who frequently exercise were more likely to be aware of their diabetic conditions than people who never or rarely exercise (OR, 2.003; 95% CI, 1.513–2.651). Conclusions: We found that the awareness and treatment of diabetes mellitus were positively associated with age and were high in participants with a family history of diabetes and those who exercise frequently, but low for cigarette smokers and alcohol drinkers. Participants with a family history of diabetes had their diabetic condition poorly controlled. [ABSTRACT FROM AUTHOR]

The composting industry has been growing rapidly in China because of a boom in the animal industry. Therefore, a rapid and accurate assessment of the quality of commercial organic fertilizers is of the utmost importance. In this study, a novel technique that combines near infrared (NIR) spectroscopy with partial least squares (PLS) analysis is developed for rapidly and accurately assessing commercial organic fertilizers quality. A total of 104 commercial organic fertilizers were collected from full-scale compost factories in Jiangsu Province, east China. In general, the NIR-PLS technique showed accurate predictions of the total organic matter, water soluble organic nitrogen, pH, and germination index; less accurate results of the moisture, total nitrogen, and electrical conductivity; and the least accurate results for water soluble organic carbon. Our results suggested the combined NIR-PLS technique could be applied as a valuable tool to rapidly and accurately assess the quality of commercial organic fertilizers. [ABSTRACT FROM AUTHOR]

Background: By comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized. Methods: From January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed. Results: There were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group. Conclusion: The lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits. [ABSTRACT FROM AUTHOR]

To solve the oversampling problem of multi-class small samples and to improve their classification accuracy, we develop an oversampling method based on classification ranking and weight setting. The designed oversampling algorithm sorts the data within each class of dataset according to the distance from original data to the hyperplane. Furthermore, iterative sampling is performed within the class and inter-class sampling is adopted at the boundaries of adjacent classes according to the sampling weight composed of data density and data sorting. Finally, information assignment is performed on all newly generated sampling data. The training and testing experiments of the algorithm are conducted by using the UCI imbalanced datasets, and the established composite metrics are used to evaluate the performance of the proposed algorithm and other algorithms in comprehensive evaluation method. The results show that the proposed algorithm makes the multi-class imbalanced data balanced in terms of quantity, and the newly generated data maintain the distribution characteristics and information properties of the original samples. Moreover, compared with other algorithms such as SMOTE and SVMOM, the proposed algorithm has reached a higher classification accuracy of about 90%. It is concluded that this algorithm has high practicability and general characteristics for imbalanced multi-class samples. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop and validate predictive models using electronic health records (EHR) data to determine whether hospitalized COVID-19-positive patients would be admitted to alternative medical care or discharged home. Methods: We conducted a retrospective cohort study using deidentified data from the University of Florida Health Integrated Data Repository. The study included 1,578 adult patients (≥18 years) who tested positive for COVID-19 while hospitalized, comprising 960 (60.8%) female patients with a mean (SD) age of 51.86 (18.49) years and 618 (39.2%) male patients with a mean (SD) age of 54.35 (18.48) years. Machine learning (ML) model training involved cross-validation to assess their performance in predicting patient disposition. Results: We developed and validated six supervised ML-based prediction models (logistic regression, Gaussian Naïve Bayes, k-nearest neighbors, decision trees, random forest, and support vector machine classifier) to predict patient discharge status. The models were evaluated based on the area under the receiver operating characteristic curve (ROC-AUC), precision, accuracy, F1 score, and Brier score. The random forest classifier exhibited the highest performance, achieving an accuracy of 0.84 and an AUC of 0.72. Logistic regression (accuracy: 0.85, AUC: 0.71), k-nearest neighbor (accuracy: 0.84, AUC: 0.63), decision tree (accuracy: 0.84, AUC: 0.61), Gaussian Naïve Bayes (accuracy: 0.84, AUC: 0.66), and support vector machine classifier (accuracy: 0.84, AUC: 0.67) also demonstrated valuable predictive capabilities. Significance: This study's findings are crucial for efficiently allocating healthcare resources during pandemics like COVID-19. By harnessing ML techniques and EHR data, we can create predictive tools to identify patients at greater risk of severe symptoms based on their medical histories. The models developed here serve as a foundation for expanding the toolkit available to healthcare professionals and organizations. Additionally, explainable ML methods, such as Shapley Additive Explanations, aid in uncovering underlying data features that inform healthcare decision-making processes. [ABSTRACT FROM AUTHOR]

The rice GA biosynthetic gene OsGA3ox1 has been proposed to regulate pollen development through the gametophytic manner, but cellular characterization of its mutant pollen is lacking. In this study, three heterozygotic biallelic variants, "-3/-19", "-3/-2" and "-3/-10", each containing one null and one 3bp-deletion allele, were obtained by the CRISPR/Cas9 technique for the functional study of OsGA3ox1. The three homozygotes, "-19/-19", "-2/-2" and "-10/-10", derived from heterozygotic variants, did not affect the development of most vegetative and floral organs but showed a significant reduction in seed-setting rate and in pollen viability. Anatomic characterizations of these mutated osga3ox1 pollens revealed defects in starch granule accumulation and pollen wall development. Additional molecular characterization suggests that abnormal pollen development in the osga3ox1 mutants might be linked to the regulation of transcription factors OsGAMYB, OsTDR and OsbHLH142 during late pollen development. In brief, the rice GA3ox1 is a crucial gene that modulates pollen starch granule accumulation and pollen wall development at the gametophytic phase. [ABSTRACT FROM AUTHOR]

Aim: In this study, we investigated the role and mechanism of Salt-induced kinase 1 (SIK1) in regulation of hepatic glucose and lipid metabolism in a high-fat food (HFD) and streptozocin (STZ)-induced type 2 diabetes mellitus (T2DM) rat model. Methods: A diabetic rat model treated with HFD plus low-dose STZ was developed and was transduced to induce a high expression of SIK1 in vivo via a tail-vein injection of a recombinant adenoviral vector. The effects on hepatic glucogenetic and lipogenic gene expression, systemic metabolism and pathological changes were then determined. Results: In T2DM rats, SIK1 expression was reduced in the liver. Overexpression of SIK1 improved hyperglycaemia, hyperlipidaemia and fatty liver, reduced the expression of cAMP-response element binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), pS577 SIK1, sterol regulatory element binding-protein-1c (SREBP-1c) and its target genes, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and increased the expression of SIK1, pT182 SIK1 and pS171 CRTC2 in diabetic rat livers with the suppression of gluconeogenesis and lipid deposition. Conclusion: SIK1 plays a crucial role in the regulation of glucose and lipid metabolism in the livers of HFD/STZ-induced T2DM rats, where it suppresses hepatic gluconeogenesis and lipogenesis by regulating the SIK1/CRTC2 and SIK1/SREBP-1c signalling pathways. Strategies to activate SIK1 kinase in liver would likely have beneficial effects in patients with T2DM and nonalcoholic fatty liver disease (NAFLD). [ABSTRACT FROM AUTHOR]

Follicle-stimulating hormone (FSH) has key roles in animal reproduction, including spermatogenesis and ovarian maturation. Many factors influence FSH secretion. However, despite the broad functions of microRNAs (miRNAs) via the regulation of target genes, little is known about their roles in FSH secretion. Our previous results suggested that miR-186-5p targets the 3′ UTR of FSHb; therefore, we examined whether miR-186-5p could regulate FSH secretion in rat anterior adenohypophyseal cells. miR-186-5p was transfected into rat anterior pituitary cells. The expression of FSHb and the secretion of FSH were examined by RT-qPCR and ELISA. A miR-186-5p mimic decreased the expression of FSHb compared with expression in the control group and decreased FSH secretion. In contrast, both the mRNA levels and secretion of FSH increased in response to miR-186-5p inhibitors. Our results demonstrate that miR-186-5p regulates FSH secretion by directly targeting the FSHb 3′ UTR, providing additional functional evidence for the importance of miRNAs in the regulation of animal reproduction. [ABSTRACT FROM AUTHOR]

Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26–38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors with high mortality worldwide. Spermatogenesis-associated serine-rich 2 (SPATS2) could be a novel diagnostic and prognostic biomarker in HCC. However, the regulatory mechanism of SPATS2 in HCC requires further elucidation. Therefore, the study's objective was to investigate this process in HCC. In this study, we found that SPATS2 is significantly upregulated in HepG2 cells to promote cell growth and migration. SPATS2 is the target transcript of lncRNA SNHG5. SPATS2 positively affects the proliferation and migration of HepG2 cells caused by the higher expression of SNHG5. Mechanistically, we identified that the elevated of SPATS2 was attributed to SNHG5 related hypomethylation of SPATS2. SNHG5 reduced the expression of DNMT3a to suppress the methylation level of SPATS2. Taken together, our results uncover a novel epigenetic regulatory mechanism of lncRNA SNHG5-DNMT3a axis-related SPATS2 expression underlying HCC progression. This may serve as a novel prognostic marker and a promising therapeutic target for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Water is essential for all living organisms. Aquaporin proteins are the major facilitator of water transport activity through cell membranes of plants including soybean. These proteins are diverse in plants and belong to a large major intrinsic (MIP) protein family. In higher plants, MIPs are classified into five subfamilies including plasma membrane intrinsic proteins (PIP), tonoplast intrinsic proteins (TIP), NOD26-like intrinsic proteins (NIP), small basic intrinsic proteins (SIP), and the recently discovered X intrinsic proteins (XIP). This paper reports genome wide assembly of soybean MIPs, their functional prediction and expression analysis. Using a bioinformatic homology search, 66 GmMIPs were identified in the soybean genome. Phylogenetic analysis of amino acid sequences of GmMIPs divided the large and highly similar multi-gene family into 5 subfamilies: GmPIPs, GmTIPs, GmNIPs, GmSIPs and GmXIPs. GmPIPs consisted of 22 genes and GmTIPs 23, which showed high sequence similarity within subfamilies. GmNIPs contained 13 and GmSIPs 6 members which were diverse. In addition, we also identified a two member GmXIP, a distinct 5th subfamily. GmMIPs were further classified into twelve subgroups based on substrate selectivity filter analysis. Expression analyses were performed for a selected set of GmMIPs using semi-quantitative reverse transcription (semi-RT-qPCR) and qPCR. Our results suggested that many GmMIPs have high sequence similarity but diverse roles as evidenced by analysis of sequences and their expression. It can be speculated that GmMIPs contains true aquaporins, glyceroporins, aquaglyceroporins and mixed transport facilitators. [ABSTRACT FROM AUTHOR]

Distracted driving is a leading cause of traffic accidents. Certain executive functions significantly affect the willingness of distracted driving; however, little research has compared the effects of executive functions on distracted driving behaviors in different aged populations. This study explores and compares the behavioral and cognitive processes underlying distracted driving behaviors in young and mature drivers. A total of 138 participants aged 18–65 years old completed a self-report questionnaire for measuring executive function index and distracted driving behaviors. Independent sample t-tests were conducted for executive functions (motivational drive, organization, strategic planning, impulse control, and empathy) and driving variables to examine any differences between young and mature groups. Partial correlation coefficients and z-score of these comparisons were calculated to compare the differences between age groups. Furthermore, multiple hierarchical regression models were constructed to determine the relative contributions of age, gender, and executive functions on distracted driving behaviors. Results demonstrated the following: (1) Mature drivers performed better for impulse control, the executive function index as well as the measure of distracted driving behavior than young drivers; (2) the relationships between executive functions and distracted driving behaviors did not significantly differ between young and mature drivers; (3) for both young and mature drivers, motivational drive and impulse control were found to significantly improve the prediction of distracted driving behavior in regression models. The findings emphasize that similar behavioral and cognitive processes are involved in distracted driving behavior of young and mature drivers, and can promote a single strategy for driver education and accident prevention interventions for both age groups. [ABSTRACT FROM AUTHOR]

Speed perception tests are already used in several countries as part of the driver licensing curriculum; however, this test is not compulsively required in China. The purpose of this study was to investigate the relationship between speed perception and eye movement for different driver groups. Forty-eight drivers, including 28 crash-involved (CI), with rear-end or side collisions, and 20 crash-not-involved (CNI) drivers, were recruited for the speed perception experiments. Drivers' reaction characteristics as well as eye movement data were analyzed. The results showed that CI drivers were more likely to overestimate the speed of visual stimuli and react in advance. The speed perception of CI drivers was more accurate than that of CNI drivers for visual stimuli with middle to high moving speeds, indicating that CNI drivers are more cautious and conservative when driving. Regarding eye movement, significant differences in saccade speed were found between the CI and CNI drivers in the occlusion area under high speed and the occlusion ratio. The relationship between visual pattern and speed perception accuracy was found to some extent. Implications of the speed perception test for the driver aptitude test were discussed. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) is an important hormone released by the pituitary gland that plays a key role in the growth and development of organisms. In our study, TargetScan analysis and the dual luciferase reporter assays were used to predict and screen for miRNAs that might act on the rat Gh1 gene, and we identified miR-543-5p. Then, the GH3 cell line and the primary rat pituitary cells were transfected with miRNA mimic, inhibitor, and siRNA. We detected the Gh1 gene expression and the GH secretion by real-time PCR and ELISAs, respectively, to verify the regulatory effect of miR-543-5p on GH secretion. The results showed that miR-543-5p can inhibit Gh1 mRNA expression and reduce GH secretion. MiR-543-5p inhibitor upregulated Gh1 mRNA expression and increased GH secretion compared with the negative control. In summary, miR-543-5p downregulates Gh1 expression, resulting in a decrease in GH synthesis and secretion, which demonstrates the important role of miRNAs in regulating GH and animal growth and development. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) contributes to the complexity of the mammalian proteome and plays an important role in diseases, including infectious diseases. The differential AS patterns of these transcript sequences between the healthy (HS3A) and mastitic (HS8A) cows naturally infected by Staphylococcus aureus were compared to understand the molecular mechanisms underlying mastitis resistance and susceptibility. In this study, using the Illumina paired-end RNA sequencing method, 1352 differentially expressed genes (DEGs) with higher than twofold changes were found in the HS3A and HS8A mammary gland tissues. Gene ontology and KEGG pathway analyses revealed that the cytokine–cytokine receptor interaction pathway is the most significantly enriched pathway. Approximately 16k annotated unigenes were respectively identified in two libraries, based on the bovine Bos taurus UMD3.1 sequence assembly and search. A total of 52.62% and 51.24% annotated unigenes were alternatively spliced in term of exon skipping, intron retention, alternative 5′ splicing and alternative 3ʹ splicing. Additionally, 1,317 AS unigenes were HS3A-specific, whereas 1,093 AS unigenes were HS8A-specific. Some immune-related genes, such as ITGB6, MYD88, ADA, ACKR1, and TNFRSF1B, and their potential relationships with mastitis were highlighted. From Chromosome 2, 4, 6, 7, 10, 13, 14, 17, and 20, 3.66% (HS3A) and 5.4% (HS8A) novel transcripts, which harbor known quantitative trait locus associated with clinical mastitis, were identified. Many DEGs in the healthy and mastitic mammary glands are involved in immune, defense, and inflammation responses. These DEGs, which exhibit diverse and specific splicing patterns and events, can endow dairy cattle with the potential complex genetic resistance against mastitis. [ABSTRACT FROM AUTHOR]

Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases. Many studies have demonstrated that heme oxygenase-1 (HO-1) is involved in diverse biological processes as a cytoprotective molecule, including anti-inflammatory, anti-oxidant, anti-apoptotic, antiproliferative, and immunomodulatory effects. However, the mechanisms of HO-1 prevention in renal interstitial fibrosis remain unknown. In this study, HO-1 transgenic (TG) mice were employed to investigate the effect of HO-1 on renal fibrosis using a unilateral ureter obstruction (UUO) model and to explore the potential mechanisms. We found that HO-1 was adaptively upregulated in kidneys of both TG and wild type (WT) mice after UUO. The levels of HO-1 mRNA and protein were increased in TG mice compared with WT mice under normal conditions. HO-1 expression was further enhanced after UUO and remained high during the entire experimental process. Renal interstitial fibrosis in the TG group was significantly attenuated compared with that in the WT group after UUO. Moreover, overexpression of HO-1 inhibited the loss of peritubular capillaries. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by HO-1 overexpression. Furthermore, HO-1 restrained tubulointerstitial infiltration of macrophages and regulated the secretion of inflammatory cytokines in UUO mice. We also found that high expression of HO-1 inhibited reactivation of Wnt/β-catenin signaling, which could play a crucial role in attenuating renal fibrosis. In conclusion, these data suggest that HO-1 prevents renal tubulointerstitial fibrosis possibly by regulating the inflammatory response and Wnt/β-catenin signaling. This study provides evidence that augmentation of HO-1 levels may be a therapeutic strategy against renal interstitial fibrosis. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Background: A novel avian-origin influenza A(H7N9) caused a major outbreak in Mainland China in early 2013. Exposure to live poultry was believed to be the major route of infection. There are limited data on how the general public changes their practices regarding live poultry exposure in response to the early outbreak of this novel influenza and the frequency of population exposure to live poultry in different areas of China. Methodology: This study investigated population exposures to live birds from various sources during the outbreak of H7N9 in Guangzhou city, China in 2013 and compared them with those observed during the 2006 influenza A(H5N1) outbreak. Adults were telephone-interviewed using two-stage sampling, stratified by three residential areas of Guangzhou: urban areas and two semi-rural areas in one of which (Zengcheng) A(H7N9) virus was detected in a chicken from wet markets. Logistic regression models were built to describe practices protecting against avian influenza, weighted by age and gender, and then compare these practices across residential areas in 2013 with those from a comparable 2006 survey. Principal Findings: Of 1196 respondents, 45% visited wet markets at least daily and 22.0% reported buying live birds from wet markets at least weekly in April-May, 2013, after the H7N9 epidemic was officially declared in late March 2013. Of those buying live birds, 32.3% reported touching birds when buying and 13.7% would slaughter the poultry at home. Although only 10.1% of the respondents reported raising backyard birds, 92.1% of those who did so had physical contact with the birds they raised. Zengcheng respondents were less likely to report buying live birds from wet markets, but more likely to buy from other sources when compared to urban respondents. Compared with the 2006 survey, the prevalence of buying live birds from wet markets, touching when buying and slaughtering birds at home had substantially declined in the 2013 survey. Conclusion/Significance: Although population exposures to live poultry were substantially fewer in 2013 compared to 2006, wet markets and backyard poultry remained the two major sources of live bird exposures for the public in Guangzhou in 2013. Zengcheng residents seemed to have reduced buying live birds from wet markets but not from other sources in response to the detection of H7N9 virus in wet markets. [ABSTRACT FROM AUTHOR]

Background: Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN. Methods: Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1–4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively. Results: After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25–34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates. Conclusions: The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN. [ABSTRACT FROM AUTHOR]

Purpose: To determine the role of brain metastases (BM) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) by performing a meta-analysis of the RCTs (randomized controlled clinical trials) and non-RCTs (non-randomized controlled clinical trials) published in the literature. Methods: A meta-analysis was performed using trials identified through PubMed, EMBASE and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included BM, OS, median survival (MS), response rate (RR), Hazard ratios (HRs) and odds ratios (ORs), and their 95% confidence intervals (CIs) were pooled using ReMan software. Results: Twelve trials (6 RCTs and 6 non-RCTs) involving 1,718 NSCLC patients met the inclusion criteria. They were grouped on the basis of study design for separate Meta-analyses. The results showed that prophylactic cranial irradiation (PCI) reduced the risk of BM as compared with non-PCI in NSCLC patients (OR = 0.30, 95% [CI]: 0.21–0.43, p<0.00001). However, HRs for OS favored non-PCI (HR = 1.19, 95% [CI]: 1.06–1.33, p = 0.004), without evidence of heterogeneity between the studies. Conclusion: Our results suggest that although PCI decreased the risk of BM, it may impose a detrimental effect on OS of NSCLC patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the prognostic value of metastatic lymph node ratio (LNR) in patients having radical resection for stage III gastric cancer. Methods: A total of 365 patients with stage III gastric cancer who underwent radical resection between 2002 and 2008 at Tianjin Medical University Cancer Institute and Hospital were analyzed. The cut-point survival analysis was adopted to determine the appropriate cutoffs for LNR. Kaplan–Meier survival curves and log-rank tests were used for the survival analysis. Results: By cut-point survival analysis, the LNR staging system was generated using 0.25 and 0.50 as the cutoff values. Pearson's correlation test revealed that the LNR was related with metastatic lymph nodes but not related with total harvested lymph nodes. Cox regression analysis showed that depth of invasion and LNR were the independent predictors of survival (p<0.05). There was a significant difference in survival between each pN stages classified by the LNR staging, however no significant difference was found in survival rate between each LNR stages classified by the pN staging. Conclusions: The LNR is an independent prognostic factor for survival in stage III gastric cancer and is superior to the pN category in TNM staging. It may be considered as a prognostic variable in future staging system. [ABSTRACT FROM AUTHOR]

Nesfatin-1 is an anorexigenic peptide involved in energy homeostasis. Recently, nesfatin-1 was reported to decrease blood glucose level and improve insulin sensitivity in high-fat diet-fed rats. However, little information is known about the influence of nesfatin-1 on lipid metabolism either in physiological or diabetic condition. This study undertook whether nesfatin-1 was involved in the pathophysiology in Streptozotocin-induced type 2 diabetic mice (T2DM), which was induced by a combination of high-calorie diet and two low-doses Streptozotocin. We observed that plasma nesfatin-1 was significantly increased while expression of nesfatin-1 neurons were decreased in hypothalamus in diabetes group compared to only high-calorie diet control group; intravenous injection of nesfatin-1 decreased 0–1h, 0–2h, 0–3h cumulative food intake in T2DM, but 0–24h total food intake had no difference between groups. Body weight and plasma FFA were normalized after nesfatin-1(10 µg/Kg) administration for 6 days. These results suggested that nesfatin-1 improved lipid disorder in T2DM. It was found that blood glucose and insulin resistance coefficient decreased with treatment of nesfatin-1 (both in 1 µg/Kg and 10 µg/Kg doses) in diabetes mice. For further understanding the role of nesfatin-1 on lipid metabolism, we detected p-AMPK and p-ACC of skeletal muscle in T2DM using western blotting. The expression of p-AMPK and p-ACC increased when nesfatin-1 was given with doses 1 µg/Kg but not in doses 10 µg/Kg. Taken together, nesfatin-1 participated in the development of T2DM and stimulated free fatty acid utilization via AMPK-ACC pathway in skeletal muscle in T2DM. [ABSTRACT FROM AUTHOR]

Intercalated disk (ID), which electromechanically couples cardiomyocytes into a functional syncitium, is closely related to normal morphology and function of engineered heart tissues (EHTs), but the development mode of ID in the three-dimensional (3D) EHTs is still unclear. In this study, we focused on the spatiotemporal development of the ID in the EHTs constructed by mixing neonatal rat cardiomyocytes with collagen/Matrigel, and investigated the effect of 3D microenvironment provided by collagen/Matrigel matrix on the formation of ID. By histological and immmunofluorescent staining, the spatiotemporal distribution of ID-related junctions was detected. Furthermore, the ultra-structures of the ID in different developmental stages were observed under transmission electron microscope. In addition, the expression of the related proteins was quantitatively analyzed. The results indicate that accompanying the re-organization of cardiomyocytes in collagen/Matrigel matrix, the proteins of adherens junctions, desmosomes and gap junctions redistributed from diffused distribution to intercellular regions to form an integrated ID. The adherens junction and desmosome which are related with mechanical connection appeared earlier than gap junction which is essential for electrochemical coupling. These findings suggest that the 3D microenvironment based on collagen/Matrigel matrix could support the ordered assembly of the ID in EHTs and have implications for comprehending the ordered and coordinated development of ID during the functional organization of EHTs. [ABSTRACT FROM AUTHOR]

Dihydromyricetin (DHM) is a major active ingredient of flavonoids compounds. It exhibited anticancer activity and induced apoptosis in human hepatocellular carcinoma HepG2 cells according to our previous data. In this study, we investigated whether p53 is involved in DHM-triggered viability inhibition and apoptosis induction in cancer cells. MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay was employed to evaluate the viability of HepG2 cells after DHM treatment. Meanwhile, p53 small interfering RNA (siRNA) was adopted to silence p53 expression. Protein level of p53 and Bax/Bcl-2 were evaluated by western blot analysis. Cell counting assay showed that DHM inhibited HepG2 cell growth effectively in a time- and dose-dependent manner. P53 expression was significantly increased after DHM treatment, whereas Bcl-2 was reduced potently. Furthermore, after co-treatment with Pifithrin-α (PFT-α, p53 inhibitor), Bcl-2 expression was reversed. The expression of Bax was no significant change, which was also observed after p53 silence. These findings defined and supported a novel function that DHM could induce human hepatocellular carcinoma HepG2 cells apoptosis by up-regulating Bax/Bcl-2 expression via p53 signal pathway. [ABSTRACT FROM AUTHOR]