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Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting (GV24) and Baihui (GV20) acupoints, with a dilatational wave (1–20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3K/Akt signaling pathway-related factors Beclin-1, mammalian target of rapamycin (mTOR), and PI3K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting (GV24) and Baihui (GV20) acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China (approval No. 8150150901) on March 10, 2016.

The current developed friction models are basically based on the assumption of the normal forces exerted between the contact surfaces known in advance, less work has been done for closed-form (i.e., analytic) modeling in complex mechanical systems where the normal forces vary greatly over time. In this paper, the closed-form representations of friction forces in mechanical systems are newly derived in a way of dynamics. The Udwadia-Kalaba equation is first used to calculate the normal force exerted by the contact surface in mechanical system. The friction force is then calculated via existing friction models. Such closed-form expressions of friction forces contain both the magnitude and direction at any instant of time, even as the normal force is nonconstant. The novel representations offer an effective way for analytically expressing friction force in dynamical systems, which makes it possible for accurate simulation and control design of dynamical systems with non-negligible friction forces.

Lung cancer is the most common primary malignant lung tumor. However, the etiology of lung cancer is still unclear. Fatty acids include short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs) as essential components of lipids. SCFAs can enter the nucleus of cancer cells, inhibit histone deacetylase activity, and upregulate histone acetylation and crotonylation. Meanwhile, PUFAs can inhibit lung cancer cells. Moreover, they also play an essential role in inhibiting migration and invasion. However, the mechanisms and different effects of SCFAs and PUFAs on lung cancer remain unclear. Sodium acetate, butyrate, linoleic acid, and linolenic acid were selected to treat H460 lung cancer cells. Through untargeted metabonomics, it was observed that the differential metabolites were concentrated in energy metabolites, phospholipids, and bile acids. Then, targeted metabonomics was conducted for these three target types. Three LC-MS/MS methods were established for 71 compounds, including energy metabolites, phospholipids, and bile acids. The subsequent methodology validation results were used to verify the validity of the method. The targeted metabonomics results show that, in H460 lung cancer cells incubated with linolenic acid and linoleic acid, while the content of PCs increased significantly, the content of Lyso PCs decreased significantly. This demonstrates that there are significant changes in LCAT content before and after administration. Through subsequent WB and RT-PCR experiments, the result was verified. We demonstrated a substantial metabolic disparity between the dosing and control groups, further verifying the reliability of the method.

Porous structures with light weight and high mechanical performance exist widely in the tissues of animals and plants. Biomimetic materials with those porous structures have been well-developed, and their highly specific surfaces can be further used in functional integration. However, most porous structures in those tissues can hardly be entirely duplicated, and their complex structure-performance relationship may still be not fully understood. The key challenges in promoting the applications of biomimetic porous materials are to figure out the essential factors in hierarchical porous structures and to develop matched preparation methods to control those factors precisely. Hence, this article reviews the existing methods to prepare biomimetic porous structures. Then, the well-proved effects of micropores, mesopores, and macropores on their various properties are introduced, including mechanical, electric, magnetic, thermotics, acoustic, and chemical properties. The advantages and disadvantages of hierarchical porous structures and their preparation methods are deeply evaluated. Focusing on those disadvantages and aiming to improve the performance and functions, we summarize several modification strategies and discuss the possibility of replacing biomimetic porous structures with meta-structures.

Piezoelectric print-heads (PPHs) are used with a variety of fluid materials with specific functions. Thus, the volume flow rate of the fluid at the nozzle determines the formation process of droplets, which is used to design the drive waveform of the PPH, control the volume flow rate at the nozzle, and effectively improve droplet deposition quality. In this study, based on the iterative learning and the equivalent circuit model of the PPHs, we proposed a waveform design method to control the volume flow rate at the nozzle. Experimental results show that the proposed method can accurately control the volume flow of the fluid at the nozzle. To verify the practical application value of the proposed method, we designed two drive waveforms to suppress residual vibration and produce smaller droplets. The results are exceptional, indicating that the proposed method has good practical application value.

Aflatoxin B1 (AFB1) is a toxic food/feed pollutant, exerting extensive deleterious impacts on the liver. Oxidative stress and inflammation are considered to be vital contributors to AFB1 hepatotoxicity. Polydatin (PD), a naturally occurring polyphenol, has been demonstrated to protect and/or treat liver disorders caused by various factors through its antioxidant and anti-inflammatory properties. However, the role of PD in AFB1-induced liver injury is still elusive. Therefore, this study was designed to investigate the protective effect of PD on hepatic injury in mice subjected to AFB1. Male mice were randomly divided into three groups: control, AFB1 and AFB1-PD groups. The results showed that PD protected against AFB1-induced hepatic injury demonstrated by the reduced serum transaminase activity, the restored hepatic histology and ultrastructure, which could be attributed to the enhanced glutathione level, the reduced interleukin 1 beta and tumor necrosis factor alpha concentrations, the increased interleukin 10 expression at transcriptional level and the up-regulated mRNA expression related to mitophagy. In conclusion, PD could alleviate AFB1-induced hepatic injury by reducing oxidative stress, inhibiting inflammation and improving mitophagy.

Chilling stress threatens the yield and distribution pattern of global crops, including the tea plant (Camellia sinensis), one of the most important cash crops around the world. Circular RNA (circRNA) plays roles in regulating plant growth and biotic/abiotic stress responses. Understanding the evolutionary characteristics of circRNA and its feedbacks to chilling stress in the tea plant will help to elucidate the vital roles of circRNAs. In the current report, we systematically identified 2702 high-confidence circRNAs under chilling stress in the tea plant, and interestingly found that the generation of tea plant circRNAs was associated with the length of their flanking introns. Repetitive sequences annotation and DNA methylation analysis revealed that the longer flanking introns of circRNAs present more repetitive sequences and higher methylation levels, which suggested that repeat-elements-mediated DNA methylation might promote the circRNAs biogenesis in the tea plant. We further detected 250 differentially expressed circRNAs under chilling stress, which were functionally enriched in GO terms related to cold/stress responses. Constructing a circRNA-miRNA-mRNA interaction network discovered 139 differentially expressed circRNAs harboring potential miRNA binding sites, which further identified 14 circRNAs that might contribute to tea plant chilling responses. We further characterized a key circRNA, CSS-circFAB1, which was significantly induced under chilling stress. FISH and silencing experiments revealed that CSS-circFAB1 was potentially involved in chilling tolerance of the tea plant. Our study emphasizes the importance of circRNA and its preliminary role against low-temperature stress, providing new insights for tea plant cold tolerance breeding.

NALCN, a sodium leak channel, plays a key role in regulating the resting membrane potential and controlling neuronal excitability. Here the authors report a cryo-EM structure of human NALCN in complex with FAM155A, that with complementary functional analyses provide insights on its ion selectivity, voltage sensing and specific interactions with auxiliary subunits.

Abstract Both E‐ and Z‐isomers of lycopene are encountered in nature. Although they were separated on C30‐HPLC by the mobile phase consisting of CH3CN‐MeOH (A) and MTBE (B), the quantification of Z‐isomers cannot be archived at present because either their commercially available reference samples are currently lacking, or they are unstable. In this study, both the specific and molar absorption coefficients of 5, 9, and 13 Z‐isomers in the mobile phase were determined on the analytical C30‐HPLC‐PDA‐ELSD, and further verified on the preparative C30‐HPLC‐PDA. The specific and molar absorption coefficients of 5, 9, and 13 Z‐isomers were finally verified to be A1cm1% = 3,422 and εmol = 183,717, A1cm1% = 2,183 and εmol = 117,199, and A1cm1% = 1,119 and εmol = 60,076, respectively, in the mobile phase. With these determined coefficients, the quantifications of 5, 9, and 13 Z‐isomers were able to be archived on C30‐HPLC‐PDA with the mobile phase applied in this investigation.

In order to understand the inherent vibration characteristics of multi-motor parallel drive-transmission system， and reveal the influence of system stiffness parameters on its natural frequency， considering the nonlinear factors such as time-varying meshing stiffness and messing error， the coupling dynamics model of multi-motor parallel drive-transmission system is established by using lumped-mass method. According to the trait of the vibration displacement of center components， the three typical low-order vibration modes are given， that is， torsional vibration mode， transverse vibration model and planet vibration mode. Then， the influence of meshing stiffness and support stiffness on the natural frequencies is studied. The results show that the other frequency components are sensitive to the change of system stiffness parameters except high order frequencies， and the coupling effect of system should be taken into full account when solving the natural frequency of the system. Meanwhile， the mode jumping will occur when the system stiffness parameters change， namely， a sudden change in the vibration mode of system， and it increases the complexity of the dynamic behavior of the system. Therefore， in the process of dynamic design， the mode jumping point should be avoided as much as possible to prevent the multi-order resonance from occurring.

Abstract Background Angiogenesis is important for the progression of gastric cancer (GC). Y-box binding protein 1 (YB-1) predicts advanced disease and indicates neovasculature formation in GC tissues, while the related mechanisms remain elusive. Exosomes mediate intercellular communications via transferring various molecules including proteins, lipids, mRNAs, and microRNAs, while the cargos of GC exosomes and the related mechanisms in GC angiogenesis were rarely reported except for several microRNAs. Methods In this study, human umbilical vein endothelial cells (HUVECs) were, respectively, treated by the exosomes isolated from the YB-1 transfected and the control SGC-7901 cells (SGC-7901-OE-Exo and SGC-7901-NC-Exo), and their apoptosis, proliferation, migration, invasion, and angiogenesis were, sequentially, compared. The levels of angiogenic factors including VEGF, Ang-1, MMP-9 and IL-8 in the exosome-treated HUVECs and the GC-derived exosomes were, separately, detected using PCR and Western blotting as well as RNA sequencing assays. Results We observed the consistent level of YB-1 in the exosomes and their originated GC cells, and the internalization of exosomes into HUVECs. Comparing with SGC-7901-NC-Exo, SGC-7901-OE-Exo significantly inhibited the apoptosis but promoted the proliferation, migration, invasion, and angiogenesis of HUVECs, within which the increased mRNA and protein levels of VEGF, Ang-1, MMP-9 and IL-8 were demonstrated. Meanwhile, mRNA levels of VEGF, Ang-1, MMP-9 and IL-8 showed no significant difference between SGC-7901-NC-Exo and SGC-7901-OE-Exo, although statistically higher mRNA of YB-1 was detected in the SGC-7901-OE-Exo. Conclusions Our findings illustrate YB-1 as the key component of exosome to promote GC angiogenesis by upregulating specific angiogenic factors in the exosome-treated endothelial cells but not in the exosomes themselves.

BackgroundIntrauterine devices (IUDs) are commonly used as a contraceptive method. IUD migration and colon perforation are rare but serious complications occurring sometimes years after insertion.CaseA 42-year-old woman with complaints of slight abdominal pain underwent a colonoscopy. Colonoscopy showed that a “nail” had penetrated the ascending colon wall and that an arm of the “nail” was embedded in the colon wall. We did not remove the “nail” rashly under colonoscopy. Considering the safety and effectiveness of the patient's operation, we were able to remove the “nail” easily by performing laparoscopic-endoscopic cooperative surgery (LECS) combined with hysteroscopy at the same time.ConclusionWe report a case of successful removal of a colonic perforation device by colonoscopy, laparoscopy, and hysteroscopy, which is the first method used.

ObjectiveChildhood obesity is one of the most severe challenges of public health in the twenty-first century and may increase the risk of various physical and psychological diseases in adulthood. The prevalence and predictors of unreported results and premature termination in pediatric obesity research are not clear. We aimed to characterize childhood obesity trials registered on ClinicalTrials.gov and identify features associated with early termination and lack of results reporting.MethodsRecords were downloaded and screened for all childhood obesity trials from the inception of ClinicalTrials.gov to July 29, 2021. We performed descriptive analyses of characteristics, Cox regression for early termination, and logistic regression for lack of results reporting.ResultsWe identified 1,312 trials registered at ClinicalTrials.gov. Among clinicalTrials.gov registered childhood obesity-related intervention trials, trial unreported results were 88.5 and 4.3% of trials were prematurely terminated. Additionally, the factors that reduced the risk of unreported outcomes were US-registered clinical studies and drug intervention trials. Factors associated with a reduced risk of early termination are National Institutes of Health (NIH) or other federal agency funding and large trials.ConclusionThe problem of unreported results in clinical trials of childhood obesity is serious. Therefore, timely bulletin of the results and reasons for termination remain urgent aims for childhood obesity trials.

Daily foods contain a great number of self-assembled nanoparticles (NPs) which were incidentally produced during food processing. These food incidental NPs can directly access the human gastrointestinal tract in high frequency and large quantities. Limited reports were focused on whether and how these food incidental NPs affected the gastrointestinal tissues and gut microbiota. In the present study, bone soup and its NPs both significantly ameliorated colitis symptoms in dextran sulfate sodium (DSS)-induced mice and inhibited the release of pro-inflammatory cytokines. They also restored intestinal microbiota dysbiosis by improving the diversity and richness of intestinal microbiota and regulating community composition, such as a remarkable increase in Muribaculaceae, Alistipes, and Alloprevotella, and a decrease in Helicobacter. Moreover, the correlation analysis showed that pro-inflammatory cytokines were negatively correlated with Muribaculaceae, Alloprevotella, and Alistipes, but positively correlated with Helicobacter. These findings suggest that the food incidental NPs can influence human health through regulating the inflammation of the gastrointestinal tissues and the gut microbiota.

Although vitrification has been widely applied in assisted reproductive technology, it is unknown whether storage time has any impact on the mRNA and lncRNA expression profiles in human embryos. Eleven women (aged 23–35 years) who had undergone in vitro fertilization treatment were recruited for this study. The transcriptomes of 3 fresh eight-cell embryos and 8 surviving vitrified-warmed eight-cell embryos (4 embryos were cryostored for 3 years, and the others were cryostored for 8 years) were analyzed through single-cell RNA-Seq. No differentially expressed mRNAs or lncRNAs were identified between the 3-years group and 8-years group. A total of 128 mRNAs and 365 lncRNAs were differentially expressed in the 8 vitrified-warmed embryos compared with the fresh embryos. The vitrification-warming impact was moderate, and it was mainly related to the pathways of metabolism, stress response, apoptosis, cell cycle, cell adhesion, and signaling for TFG-β and Hippo. The analysis of target mRNAs suggested that lncRNAs might contribute to the regulation of mRNAs after vitrification-warming. Our findings indicated that long-term storage after vitrification does not affect the mRNA and lncRNA expression profiles in human embryos, however, the procedure of vitrification-warming would lead to minor alteration of transcriptome.

Populus not only has significant economic and ecological values, but also serves as a model tree that is widely used in the basic research of tree growth, physiology, and genetics. However, high levels of morphological variation and extensive interspecific hybridization of Populus pose an obstacle for taxonomy, and also to the understanding of phylogenetic interspecific relationships and biogeographical history. In this study, a total of 103 accessions representing almost all the wild species of Populus were collected and whole-genome re-sequenced to examine the phylogenetic relationships and biogeography history. On the basis of 12,916,788 nuclear single nucleotide polymorphisms (SNPs), we reconstructed backbone phylogenies using concatenate and coalescent methods, we highly disentangled the species relationships of Populus, and several problematic taxa were treated as species complexes. Furthermore, the phylogeny of the chloroplast genome showed extensive discordance with the trees from the nuclear genome data, and due to extensive chloroplast capture and hybridization of Populus species, plastomes could not accurately evaluate interspecies relationships. Ancient gene flow between clades and some hybridization events were also identified by ABBA–BABA analysis. The reconstruction of chronogram and ancestral distributions suggested that North America was the original region of this genus, and subsequent long dispersal and migration across land bridges were contributed to the modern range of Populus. The diversification of Populus mainly occurred in East Asia in recent 15 Ma, possibly promoted by the uplift of the Tibetan Plateau. This study provided comprehensive evidence on the phylogeny of Populus and proposed a four-subgeneric classification and a new status, subgenus Abaso. Meanwhile, ancestral distribution reconstruction with nuclear data advanced the understanding of the biogeographic history of Populus.

Objective This study investigated the peripheral Th17/Treg balance and its potential controlling factor indoleamine 2,3 dioxygenase (IDO) in patients with periodontitis and atherosclerosis (AS), as well as its correlation with Porphyromonas gingivalis infection. Methods In this retrospective study, P. gingivalis -infected atherosclerotic patients (Pg-AS), atherosclerotic patients (AS), P. gingivalis -infected periodontitis patients (Pg), and healthy controls (HCs) were selected after clinical examination, subgingival plaque examination, and plasma anti- P. gingivalis antibody analysis. Treg and Th17 cell percentages, related transcription factors, and functional cytokines in peripheral blood were analysed. Plasma tryptophan (Trp) and kynurenine (Kyn) were measured to determine IDO activity. Results Atherosclerotic patients (Pg-AS and AS groups) had significantly lower IDO activity and higher Th17/Treg ratio than those in the Pg and HC groups. The Th17/Treg ratio was higher and IDO activity was lower in the Pg-AS group compared with the AS group. Transcription factors and cytokines exhibited the same trend as the Th17 and Treg cells. Additionally, IDO activity was negatively correlated with the plasma anti- P. gingivalis antibody titre and the Th17/Treg ratio in the atherosclerotic group. Conclusions P. gingivalis may reduce IDO activity and further promote Th17/Treg imbalance to facilitate AS development. IDO may be a novel molecular marker to predict periodontitis-associated AS.

BackgroundImpulse oscillometry (IOS) can be used to evaluate airway impedance in patients with obstructive airway diseases. Previous studies have demonstrated that IOS parameters differ between patients with bronchiectasis and healthy controls. This study aims to explore the usefulness of IOS in assessing disease severity and airway reversibility in patients with bronchiectasis.MethodSeventy-four patients with non-cystic fibrosis bronchiectasis who visited our Respiratory Medicine outpatient clinic were consecutively recruited. Spirometry, plethysmography and IOS tests were performed. Patients were stratified into mild, moderate and severe disease according to Reiff, Bhalla, BSI, FACED, and BRICS scores. Airway reversibility was measured by bronchodilation test (BDT) and the result was classified as positive or negative. ROC curves of IOS parameters were used to assess the usefulness of IOS parameters in predicting airway reversibility. Correlations between the IOS, spirometric lung function and bronchiectasis severity parameters were analyzed.ResultsMany IOS parameters, such as airway resistance at 5 Hz (R5), small airways resistance (R5–R20), total airway reactance (X5), resonance frequency (Fres), total airway impedance at 5 Hz (Z5), and peripheral resistance (Rp) increased in patients with bronchiectasis who presented a moderate to severe severity as categorized by the FACED, BSI and Reiff scores. Large airway resistance (R20) and central resistance (Rc) were not significantly different among groups with different bronchiectasis severity. The difference between R5 and R20 (R5-R20) showed 81.0% sensitivity, and 69.8%specificity in predicting the airway reversibility in bronchiectasis with AUC of 0.794 (95%CI, 0.672–0.915).ConclusionIOS measurements are useful indicators of bronchiectasis severity and may be useful for predicting the airway reversibility.

Efficient and accurate flight trajectory prediction is a key technology for promoting intelligent and informative air traffic management and improving the operational capabilities and predictability of air traffic. To address the problems in extracting hidden information from historical trajectory information, the approach must accurately select high-dimensional features related to the prediction target and overcome the short-term memory of the time series. Herein, we present a novel trajectory prediction model based on a dual-self-attentive (DSA)-temporal convolutional network (TCN)-bidirectional gated recurrent unit (BiGRU) neural network. In this model, the TCN provides highly stable training, high parallelism, and a flexible perceptual domain. The self-attentive mechanism of the TCN structure can focus on features that contribute the most to the output. After the TCN, the BiGRU network combined with the self-attentive mechanism is used to further bidirectionally mine the connections between the features and outputs of the trajectory sequence, and a Bayesian algorithm is used to optimise the hyperparameters of the model for optimal performance. A comparison and validation based on current well-known neural network models (i.e., CNN, TCN, GRU, and their variants) shows that the DSA-TCN-BiGRU model based on Bayesian hyperparameter optimisation has the best performance. Therefore, the improved predictive model is applicable and valuable, providing a basis for future decision trajectory-based operations.

Myocardial ischemia/reperfusion (I/R) injury seriously threats the health and life of patients with ischemia heart disease. Herein, we probed the potential influence of myosin 1b (myo1b) on hypoxia/reoxygenation- (H/R-) stimulated cardiomyocyte H9c2 cell apoptosis and autophagy. After H/R stimulation, the myo1b mRNA level in H9c2 cells was tested via qRT-PCR. Myo1b overexpression plasmid (OE-myo1b) and small interfering RNA (siRNA) targeting myo1b (si-myo1b) were transfected into H9c2 cells to alter myo1b expression in H9c2 cells. Following H/R stimulation and/or OE-myo1b (or si-myo1b) transfection, H9c2 cell apoptosis, proliferation, and autophagy were detected, respectively. We found that H/R stimulation reduced the mRNA level of myo1b in H9c2 cells and resulted in H9c2 cell apoptosis, proliferation inhibition, and autophagy. Overexpression of myo1b reversed the H/R-resulted H9c2 cell apoptosis, proliferation inhibition, and autophagy. Silence of myo1b had opposite effects, which promoted H9c2 cell apoptosis, reduced cell proliferation, and accelerated cell autophagy. Taken together, Myo1b took part in the modulation of H/R-stimulated cardiomyocyte apoptosis and autophagy, which might be serve as a potential endogenous target for prevention and therapy of I/R injury.

Global issues such as global warming, rising sea level, melting Arctic and Antarctic glaciers, deterioration of the natural environment, and depletion of fossil energy have attracted increasing attention. As the concept of environmental protection has become increasingly popular, the concept of new energy automobiles has been proposed to keep the heat up. Especially in recent years, with the advantages of energy conservation, environmental protection, and low noise, new energy automobiles have changed from concept to industry and have been generally accepted and recognized by consumers in the consumer market. The increasingly stringent energy crisis and emission regulations have put forward more stringent requirements for modern automobiles. The thermal management of the new generation of intelligent automobiles is not only limited to simply solving the problem of engine heat dissipation but also involves reliability, power, economy, emissions, and comfort. It is an important vehicle development technology with many performances such as performance. The integrated thermal management of new energy vehicles includes engine cooling, oil cooling, air conditioning refrigeration, HVAC heating, supercharged intercooling, low cycle thermal fatigue, and thermal damage. For new energy vehicles such as hybrid and pure electric vehicles, it also includes motor cooling, motor controller cooling, and power battery temperature control. For the purpose of vehicle thermal management optimization design, this paper innovatively proposes IVTM technical solutions, relying on multidimensional numerical calculation coupling and multiobjective collaborative optimization control to integrate system design, scheme evaluation, performance analysis, dynamic control, and collaborative optimization. Through the integrated thermal management collaborative control strategy based on the full operating conditions of the new energy vehicle, the comprehensive improvement of multiple evaluation indicators such as system design performance, thermal management, and control performance and economy is achieved.

Objective: Abnormal selective attention to drug cues and negative affect is observed in patients with substance dependence, and it is closely associated with drug addiction and relapse. Methadone maintenance is an effective replacement therapy to treat heroin addiction, which significantly reduces the relapse rate. The present study examines whether the patients with opioid use disorder on chronic methadone maintenance therapy exhibit abnormal attentional bias to drug cues and negative-affective cues. Moreover, its relation to therapeutic and neuropsychological factors is also examined.Methods: Seventy-nine patients with opioid use disorder under chronic methadone maintenance therapy and 73 age-, sex-, and education-matched healthy controls were recruited and assessed for attentional bias to drug cues and negative affect using a dot-probe detection task. Correlational analysis was used to examine the relationships between the attentional bias and the demographic, therapeutic, and neuropsychological factors.Results: No significant overall patient-control group difference is observed in drug-related or negative-affective-related attentional bias scores. In the patient group, however, a significant negative correlation is found between the attentional bias scores to negative-affective cues and the duration of methadone treatment (p = 0.027), with the patients receiving longer methadone treatment showing less attentional avoidance to negative-affective cues. A significant positive correlation is found between the negative affect-induced bias and the impulsivity score (p = 0.006), with more impulsive patients showing higher attentional avoidance to negative affective cues than less impulsive patients. Additionally, the patients detect a smaller percentage of probe stimuli following the drug (p = 0.029) or negative-affective pictures (p = 0.009) than the healthy controls.Conclusion: The results of the present study indicate that the patients under chronic methadone maintenance therapy show normalized attentional bias to drug and negative-affective cues, confirming the involuntary attention of the patients is not abnormally captured by external drug or negative-affective clues. Our findings also highlight that the attentional avoidance of negative-affective cues is modulated by the duration of methadone treatment and the impulsivity level in the patients.

Background. Coronavirus disease 2019 (COVID-19) has been a global threat that pushes healthcare to its limits. Hypertension is one of the most common risk factors for cardiovascular complications in COVID-19 and is strongly associated with disease severity and mortality. To date, clinical mechanisms by which hypertension leads to increased risk in COVID-19 are still unclear. Furthermore, additional factors might increase these risks, such as the consideration of age and sex, which are of interest when in search of personalized treatments for hypertensive COVID-19 patients. Methods. We conducted a retrospective cohort study of 543 COVID-19 patients in seven provinces of China to examine the epidemiological and clinical characteristics of COVID-19 in this population and to determine risk factors of hypertensive COVID-19 patients. We also used univariable and multivariable logistic regression methods to explore the risk factors associated with hypertensive COVID-19 patients in different age and sex subgroups. Results. Among the enrolled COVID-19 patients, the median age was 47 years (interquartile range (IQR) 34.0–57.0), and 99 patients (18.23%) were over 60 years old. With regard to comorbidities, 91 patients (16.75%) were diagnosed with hypertension, followed by diabetes, coronary disease, and cerebrovascular disease. Of the hypertensive COVID-19 patients, 51 (56.04%) were male. Multivariable analysis showed that old age, comorbid diabetes or coronary heart disease on admission, increased D-dimer, increased glucose, and decreased lymphocyte count were independent risk factors associated with hypertensive COVID-19 patients. Elevated total bilirubin (odds ratio [OR]: 1.014, 95% confidence interval [CI]: 0.23–1.05; p=0.043) and triglycerides (OR: 1.173, 95% CI: 0.049–1.617; p=0.007) were found to be associated with elderly hypertensive COVID-19 patients. In addition, we found that decreased lymphocytes, basophil, high-density lipoprotein, and increased fibrinogen and creatinine were related to a higher risk of disease severity in male patients. The most common abnormal clinical findings pertaining to female hypertensive COVID-19 patients were hemoglobin, total bile acid, total protein, and low-density lipoprotein. Conclusions. Factors associated with increased risk of hypertensive COVID-19 patients were identified. Results to the different age and sex subgroups in our study will allow for better possible personalized care and also provide new insights into specific risk stratification, disease management, and treatment strategies for COVID-19 patients with hypertension in the future.

Aim. This retrospective study is aimed at evaluating the outcomes of a modified peroral endoscopic myotomy (POEM) technique in patients with type II achalasia. Methods. We performed a modified POEM procedure, which involved a shorter (total myotomy length=4 cm), full-thickness myotomy, on 31 patients with type II achalasia. Clinical success rates, technical success rates, pre- and postoperative esophageal manometry results, complications, and reflux-related adverse events were evaluated. Results. The clinical success (Eckardt score≤3) rates were 100% and 88.9% within 2 years and beyond 2 years postoperatively, respectively. The median lower esophageal sphincter pressures (LESP) decreased from 31.6 (26.7-49.7) mmHg preoperatively to 13.4 (10.5-21.6) and 11.8 (7.4-16.7) mmHg (P

Abstract Background In this study we aimed to identify a prognostic signature in BRCA1/2 mutations to predict disease progression and the efficiency of chemotherapy ovarian cancer (OV), the second most common cause of death from gynecologic cancer in women worldwide. Methods Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from data obtained from The Cancer Genome Atlas (TCGA) database. The area under the curve of the receiver operating characteristic curve was assessed, and the sensitivity and specificity of the prediction model were determined. Results A signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as the basis for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The three-year overall survival (OS) rates for the high- and low-risk group were approximately 38 and 100%, respectively. Chemotherapy treatment survival rates indicated that the high-risk group had significantly lower OS rates with adjuvant chemotherapy than the low-risk group. The one-, three-, and five-year OS were 100, 40, and 15% respectively in the high-risk group. The survival rate of the high-risk group declined rapidly after 2 years of OV chemotherapy treatment. Multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development. Conclusion In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with BRCA1/2 mutations, and can be used to predict prognosis and the efficiency of chemotherapy.

Abstract For the scattering problems of acoustic wave for an open arc in two dimensions, we give a uniqueness and existence analysis via the single layer potential approach leading to a system of integral equations that contains a weakly singular operator. For its numerical solutions, we describe an O ( h 3 ) $O(h^{3})$ order quadrature method based on the specific integral formula including convergence and stability analysis. Moreover, the asymptotic expansion of errors with odd power O ( h 3 ) $O(h^{3})$ is got and the Richardson extrapolation algorithm (EA) is used to improve the accuracy of numerical solutions. The efficiency of the method is illustrated by a numerical example.

Abstract Background Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma (EBV-GCLS) is a rare variant of early gastric carcinomas. Clinicopathological features of this variant remain obscure, especially in Chinese patients. Therefore, we collected EBV-GCLS cases and studied clinicopathology and prognosis. Methods By a retrospective review of 595 consecutive radical gastrectomies for early gastric carcinoma from 2006 to 2018, we identified 8 (1.3%, 8/595) EBV-GCLS cases. Clinicopathologic characteristics were compared between EBV-GCLSs and 109 conventional early gastric carcinomas, which were divided into intramucosal, SM1, and SM2 subgroups. The latter 2 subgroups were classified according to the submucosal invasion depth below or over 500 μm. Results All 8 EBV-GCLSs occurred in male patients and invaded deep submucosa (SM2) without lymph node metastasis (LNM), four (50%) of which had synchronous non-gastric malignant tumors (3 gastric gastrointestinal stromal tumors and 1 primary clear cell renal cell carcinoma), and four (50%) arose in the proximal stomach. Compared to conventional early gastric carcinomas, EBV-GCLS was significantly more frequent with SM2 invasion, poor differentiation, and synchronous non-gastric carcinoma tumor, but not with age, gender, macroscopic type, location, size, perineural invasion, lymphovascular invasion, and pathologic stage. In invasion-depth stratified comparisons in the SM2 subgroup, the frequency of LNM in EBV-GCLS was significantly lower than that in conventional early gastric carcinomas (p

Abstract Purpose To test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiotherapy (PBMS-IMRT) in reducing grade 2 or higher hematological toxicity (HT2+) for patients with cervical cancer treated with concurrent chemoradiotherapy. Methods and materials A total of 164 patients with Stage Ib2–IIIb cervical cancer were prospectively enrolled from March 2018 to March 2019 at a single center and were randomly allocated into the PBMS group or the control group. The control group received weekly cisplatin concurrently with IMRT, followed by intracavitary brachytherapy. The PBMS group additionally received PBM dose constraint. The dosimetric parameters of the pelvic bone (PB) and the subsites including hip bone (HIP) and lumbosacral spine (LSS) and the corresponding bone marrow were recorded. The endpoint of the trial was acute hematologic or gastrointestinal toxicity. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results Eighty-two patients in the PBMS group and 82 in the control group were enrolled for statistical analysis. The incidence of HT2+ in the PBMS group was 50.0%, significantly lower than the 69.5% incidence in the control group (P = 0.02). Patients with PB V40 ≥ 28% were more likely to experience HT2+ (OR = 2.85, P = 0.006), while the incidence of grade 2 or higher gastrointestinal toxicity (GT2+) events did not differ significantly between the two groups (P > 0.05). Dosimetric parameters of LSS showed stronger associations with HT2+ than other subsites. The patients with LSS V10 ≥ 87% and LSS mean ≥ 39 Gy were more likely to experience HT2+ (OR = 3.13, P = 0.001;OR = 3.03, P = 0.002, respectively). Conclusion PBMS-IMRT reduced HT compared with IMRT alone. Efforts to maintain LSS V10

Abstract Background Previous studies found that cell-free DNA (cfDNA) generated from tumors was shorter than that from healthy cells, and selecting short cfDNA could enrich for tumor cfDNA and improve its usage in early cancer diagnosis and treatment monitoring; however, the underlying mechanism of shortened tumor cfDNA was still unknown, which potentially limits its further clinical application. Results Using targeted sequencing of cfDNA in a large cohort of solid tumor patient, sequencing reads harboring tumor-specific somatic mutations were isolated to examine the exact size distribution of tumor cfDNA. For the majority of studied cases, 166 bp remained as the peak size of tumor cfDNA, with tumor cfDNA showing an increased proportion of short fragments (100-150 bp). Less than 1% of cfDNA samples were found to be peaked at 134/144 bp and independent of tumor cfDNA purity. Using whole-genome sequencing of cfDNA, we discovered a positive correlation between cfDNA shortening and the magnitude of chromatin inaccessibility, as measured by transcription, DNase I hypersensitivity, and histone modifications. Tumor cfDNA shortening occurred simultaneously at both 5′ and 3′ ends of the DNA wrapped around nucleosomes. Conclusions Tumor cfDNA shortening exhibited two distinctive modes. Tumor cfDNA purity and chromatin inaccessibility were contributing factors but insufficient to trigger a global transition from 166 bp dominant to 134/144 bp dominant phenotype.

Abstract Video streaming is critical in IoT systems, enabling a variety of applications such as traffic monitoring and health caring. Traditional adaptive bitrate streaming (ABR) algorithms mainly focus on improving Internet video streaming quality where network conditions are relatively stable. These approaches, however, suffer from performance degradation at IoT edge. In IoT systems, the wireless channels are prone to interference and malicious attacks, which significantly impacts Quality-of-Experience (QoE) for video streaming applications. In this paper, we propose a secure and network-state-aware solution, SASA, to address these challenges. We first study the buffer-level constraint when increasing bitrate. We then analyze the impact of throughput overestimation in bitrate decisions. Based on these results, SASA is designed to consist of both an offline and an online phase. In the offline phase, SASA precomputes the best configurations of ABR algorithms under various network conditions. In the online phase, SASA adopts an online Bayesian changepoint detection method to detect network changes and apply precomputed configurations to make bitrate decisions. We implement SASA and evaluate its performance using 429 real network traces. We show that the SASA outperforms state-of-the-art ABR algorithms such as RobustMPC and Oboe in the IoT environment through extensive experiments.

Abstract Objective This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

Background: Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well. Objective: To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice. Methods: Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA kits. Quantitative RT-PCR was performed to detect the transcript amounts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis. Results: The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway. Conclusion: Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.

Polymer crosslinking in desalination membranes adds stability on the cost of molecular transportation rates through the membrane. Here the authors tailor crosslinking of desalination membranes to overcome the stability and transport trade-off, and demonstrate a pervaporation desalination thin-film composite membrane with high water flux.

Abstract Background Colorectal cancer, one of the most common digestive tumors with high mortality and morbidity worldwide, currently lacks effective therapies available to improve the prognosis. This study was aimed to investigate the potency of Scutellarin against colorectal cancers, and explore the related mechanism via genomic and proteomic analysis. Methods Cell counting kit-8 assay was employed to detect the viability of HCT-116 and RKO cell lines treated with Scutellarin. The apoptosis of HCT-116 and RKO cells after Scutellarin administration was determined by TUNEL staining and Caspase 3/7 activity. Cell cycle was detected by flow cytometry analysis. The wound healing and transwell invasion test detected the role of Scutellarin in migration and invasion of HCT-116 and RKO cells. Meanwhile, the energy metabolism and growth of tumor tissues in vivo at day 28 were observed by PET-CT after Scutellarin administration with 50 mg/kg, 100 mg/kg and 300 mg/kg into 4-week-old nude mice. Blood routine and liver functions were also detected to evaluate the side effect of Scutellarin. Furthermore, the disease and function classifications which the differentially expressed genes and proteins involved after Scutellarin treatment were determined by genomic and proteomic analysis respectively. Results The Scutellarin inhibited the migration and increased apoptosis of HCT-116 and RKO cell lines. Besides, Scutellarin treatment substantially decreased the growth and volume of colorectal tumors in nude mice without side effects on the blood routine and liver function. The differentially expressed genes in RKO cells after Scutellarin administration were mainly enriched in cell death and survival, organismal injury and abnormalities, and cancer. In addition, forty-seven upregulated and twenty-nine downregulated proteins were identified. Functional clustering analysis exhibited enriched biological processes, cellular components, molecular functions and related pathways of these proteins in cellular metabolic. Then protein–protein interactions analysis showed the regulatory relationship among these differentially expressed proteins. Conclusions Taken together, the present findings revealed that Scutellarin exerted significant antitumor effect with no side effects in the blood and liver by regulating various important molecules in tumor proliferation, apoptosis and metastasis.

Abstract Background Emergency department (ED) visits or hospitalizations should prompt review of the patient’s medications after discharge and targeted deprescribing to reduce ongoing risks. Objective To see if this is happening, we sought to examine the proportion of serious falls and delirium that were followed by a prescription fill for a bladder antimuscarinic. Our secondary objective was to identify concurrent use of other anticholinergics, cholinesterase inhibitors (ChEIs), and diuretics among people with dementia taking bladder antimuscarinics. Methods Retrospective descriptive study using data from the National Health and Aging Trends Study (2011–2014) linked with Medicare claims from 2010–2014. The primary outcome was the proportion of serious falls or delirium that were followed by a bladder antimuscarinic prescription fill within 12 months. The secondary outcome was the proportion of individuals concurrently receiving prescriptions for bladder antimuscarinics, other strong anticholinergics, ChEIs, and diuretics. Results During the observation period, 8.88% of people with dementia filled a bladder antimuscarinic prescription. Over one-third (35%) initiated use after being identified as having dementia. Many used bladder antimuscarinics concurrently with other strong anticholinergics (19%), diuretics (42%), and ChEIs (32%). The majority (76%) of serious falls or delirium among people with dementia and bladder antimuscarinic use were followed by a bladder antimuscarinic prescription within 12 months. Conclusions In this descriptive study, bladder antimuscarinic prescriptions were often filled irrespective of dementia status, serious falls, or delirium. Concurrent use of other anticholinergics, diuretics, and ChEIs was common. Falls and delirium should trigger review of the medication list after discharge and targeted deprescribing in people with dementia.

Background: The aim of this study was to investigate the effects of transcatheter arterial chemoembolization (TACE) combined with sorafenib on tumor angiogenesis. Materials and methods: Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups, which received either normal saline (A), TACE (B), sorafenib (C), sorafenib followed by TACE (D), or TACE followed by sorafenib (E). Serum vascular endothelial growth factor (VEGF) levels were measured before and after TACE via ELISA. Immunohistochemistry for CD34 was performed to evaluate microvessel density (MVD), and ultrasonography was used to access tumor volume. Results: VEGF levels declined in group C but increased significantly on the 3rd post-operative day in groups B, D, and E. Levels decreased after the 7th post-operative day. Peak levels were significantly lower in group D than in groups B and E. On the 14th post-operative day, VEGF levels were the lowest in group C, followed by those in groups D and B. MVD was the lowest in group C followed by that in group D and E, and was the highest in group B. Group D had the smallest tumor volume. HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern, whereas in groups B, D, and E, large areas of tumor cell necrosis were visible. Conclusion: TACE can up-regulate serum VEGF levels, which in turn accelerates the formation of new blood vessels. Thus, TACE combined with sorafenib inhibits VEGF and angiogenesis, and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration. Keywords: Transcatheter arterial chemoembolization (TACE), Sorafenib, Hepatocellular carcinoma, Vascular endothelial growth factor (VEGF), Microvessel density (MVD)

Abstract Background Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells in the tumor microenvironment, and in regulating cancer proliferation, migration and invasion through their cargo molecules. Methods We analyzed the pro-invasiveness of exosomal circRNA-100,338 in HCC using the transwell invasion assay. The co-culture of human umbilical vein endothelial cells (HUVEC) and exosomes derived from HCC cell lines were used to evaluate the impact of HCC derived exosomes on HUVEC. Nude mice models were used to validate the findings in vitro. Clinically, quantitative RT-PCR was used to quantify the expression of serum exosomal circRNA-100,338 in HCC patients at both pre-surgery within one week and post-surgery within three weeks. Results We aim to investigate the pro-invasive role of exosomal circRNA-100,338 in HCC metastasis. We for the first time demonstrated that circRNA-100,338 was highly expressed in both highly metastatic HCC cells and their secreted exosomes. The transwell invasion assay showed that the overexpression or knockdown of exosomal circRNA-100,338 significantly enhanced or reduced the invasive abilities of HCC cells. Subsequently, in vitro and in vivo assays showed that exosomal circRNA-100,338 affected the cell proliferation, angiogenesis, permeability, and vasculogenic mimicry (VM) formation ability of human umbilical vein endothelial cells (HUVEC), and tumor metastasis. Furthermore, we also observed that the persistent high expression of exosomal circRNA-100,338 in serum of HCC patients who underwent curative hepatectomy may be a risk indicator of pulmonary metastasis and poor survival. Conclusions Our findings indicated that metastatic ability of HCC cells could be enhanced by transferring exosomal circRNA-100,338 to recipient HUVECs, which could affect proangiogenic activity by regulating angiogenesis.

In order to satisfy higher requirements for data transmission rate and system capacity, millimeter wave (mmWave) with abundant spectrum resources has be exploited and become a research hotspot of the fifth generation (5G) mobile communication systems. However, introducing mmWave technologies into cellular networks also faces many severe challenges, especially the initial user equipment (UE) discovery. In the UE discovery, the narrow-beam directional scanning is often used to search the UE, but it increases the control overhead of the system and brings about a non-negligible search delay. In this paper, we will analyze the average search delay of mmWave systems under two different UE access methods, i.e., the random scanning access method in independent networks and the search method based on UE location in heterogeneous networks. Taking the average search times discovering UEs as a measure and the number of search sectors in beam-space as an optimization parameter, the optimal number of sectors with the maximum capacity is obtained so that the search delay and the capacity can be balanced. The simulation results verify the correctness of the analysis and show that the performance of the user discovery method in heterogeneous networks is better than that of the random scan access method in mmWave independent networks.

The online monitoring of pointing error (PE) caused by the main reflector (MR) deformation under wind disturbance has become a knotty problem for large reflector antennas. This paper presents a real-time estimation algorithm for monitoring wind-induced PE by optimized acceleration measurement points. First, based on an unbiased minimum-variance input-state estimation theory via accelerations measurement, we set up the PE observation model which illustrates the relation between the structural vibration state and PE. Moreover, compared with the frequency domain integration approach, the non-integral observation model without introducing a low-frequency-cut filter can sense pseudo-static and low-frequency PE. Second, a sensor placement method considering sensor constraint spacing (SPMCSCS) is proposed to achieve a high-quality monitoring effect with low information redundancy. In the method, the constraint spacing between sensors is determined by a novel scan recognition algorithm in which regional division, and regional correlation analysis of the modal shape are carried out successively. Finally, the simulation implementation of a 7.3-m antenna under a wind disturbance is used to illustrate the algorithm.

Background/Aim: To study the impact of computer-aided detection (CADe) system on the detection rate of polyps and adenomas in colonoscopy. Materials and Methods: A total of 1026 patients were prospectively randomly scheduled for colonoscopy with (the CADe group, CADe) or without (the control group, CON) the aid of the CADe system, together with visual notification and voice alarm, so as to compare the detection rate of polyp. Results: Compared with group CON, the detection rate of adenomas increased in group CADe, the average number of adenomas increased, the number of small adenomas increased, the number of proliferative polyps increased, and the differences were statistically significant (P < 0.001), but the comparison for the number of larger adenomas showed no significant difference between the groups (P> 0.05). Conclusions: The CADe system is feasible for increasing the detection of polyps and adenomas in colonoscopy.

A single-nucleotide polymorphism (SNP) is an alteration in one nucleotide in a certain position within a genome. SNPs are associated with disease susceptibility. However, the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive. Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model. SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing. Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism. We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2. Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis, wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels. Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses, long-term depression and oxytocin signaling. Moreover, intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1, DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy. Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons. Our results indicate that CSRNP1, DUSP5 and LRRC25, containing SNPs, may be involved in the pathogenesis of hypoxic ischemic encephalopathy. These findings indicate a novel direction for further hypoxic ischemic encephalopathy research. This animal study was approved on February 5, 2017 by the Animal Care and Use Committee of Kunming Medical University, Yunnan Province, China (approval No. kmmu2019038). Cerebral tissue collection from a human fetus was approved on September 30, 2015 by the Ethics Committee of Kunming Medical University, China (approval No. 2015-9).

Abstract Background Muscle-invasive bladder cancer (MIBC) is originated in the muscle wall of the bladder, and is the ninth most common malignancy worldwide. However, there are no reliable, accurate and robust gene signatures for MIBC prognosis prediction, which is of the importance in assisting oncologists to make a more accurate evaluation in clinical practice. Methods This study used univariable and multivariable Cox regression models to select gene signatures and build risk prediction model, respectively. The t-test and fold change methods were used to perform the differential expression analysis. The hypergeometric test was used to test the enrichment of the differentially expressed genes in GO terms or KEGG pathways. Results In the present study, we identified three prognostic genes, KLK6, TNS1, and TRIM56, as the best subset of genes for muscle-invasive bladder cancer (MIBC) risk prediction. The validation of this stratification method on two datasets demonstrated that the stratified patients exhibited significant difference in overall survival, and our stratification was superior to three other stratifications. Consistently, the high-risk group exhibited worse prognosis than low-risk group in samples with and without lymph node metastasis, distant metastasis, and radiation treatment. Moreover, the upregulated genes in high-risk MIBC were significantly enriched in several cancer-related pathways. Notably, PDGFRB, a receptor for platelet-derived growth factor of PI3K-Akt signaling pathway, and TUBA1A were identified as two targets of multiple drugs. In addition, the angiogenesis-related genes, as well as two marker genes of M2 macrophage, CD163 and MRC1, were highly upregulated in high-risk MIBC. Conclusions In summary, this study investigated the underlying molecular mechanism and potential therapeutic targets associated with worse prognosis of high-risk MIBC, which could improve our understanding of progression of MIBC and provide new therapeutic strategies for the MIBC patients.

SUMMARY: Resveratrol is a polyphenol known to have many beneficial biological activities. In our study, we investigated the effect of supplementing chicken feed with different concentrations of resveratrol. A total of 2,160 Jingfen white egg chickens in their 210-d old were selected for this study. They were randomly distributed into 4 diet groups with 6 replicates each. Each replicate group contained 90 chickens. Diets were supplemented with 1 of 4 doses of resveratrol: 0, 200, 400, and 800 mg/kg. Relative to that in controls, the egg production rate and mean daily food intake significantly increased upon 200 mg/kg resveratrol treatment (P < 0.05). The feed-to-egg ratio also significantly diminished in these animals (P < 0.05), as did the cull/death rate. Resveratrol was also linked with extended egg shelf lives and improved sensory scores. Supplementation with 400 mg/kg resveratrol significantly reduced levels of total serum cholesterol and triglycerides and activities of alanine transaminase and aspartate transaminase (P < 0.05). These results therefore show that 200 mg/kg resveratrol supplementation improved the performance of laying hens, whereas 400 mg/kg dose was associated with better lipid metabolism, reduced egg cholesterol content, extended egg shelf life, improved antioxidant activity, and improved egg sensory scores.

Abstract Background The sequencing platform BGISEQ-500 is based on DNBSEQ technology and provides high throughput with low costs. This sequencer has been widely used in various areas of scientific and clinical research. A better understanding of the sequencing process and performance of this system is essential for stabilizing the sequencing process, accurately interpreting sequencing results and efficiently solving sequencing problems. To address these concerns, a comprehensive database, SEQdata-BEACON, was constructed to accumulate the run performance data in BGISEQ-500. Results A total of 60 BGISEQ-500 instruments in the BGI-Wuhan lab were used to collect sequencing performance data. Lanes in paired-end 100 (PE100) sequencing using 10 bp barcode were chosen, and each lane was assigned a unique entry number as its identification number (ID). From November 2018 to April 2019, 2236 entries were recorded in the database containing 65 metrics about sample, yield, quality, machine state and supplies information. Using a correlation matrix, 52 numerical metrics were clustered into three groups signifying yield-quality, machine state and sequencing calibration. The distributions of the metrics also delivered information about patterns and rendered clues for further explanation or analysis of the sequencing process. Using the data of a total of 200 cycles, a linear regression model well simulated the final outputs. Moreover, the predicted final yield could be provided in the 15th cycle of the early stage of sequencing, and the corresponding R2 of the 200th and 15th cycle models were 0.97 and 0.81, respectively. The model was run with the test sets obtained from May 2019 to predict the yield, which resulted in an R2 of 0.96. These results indicate that our simulation model was reliable and effective. Conclusions Data sources, statistical findings and application tools provide a constantly updated reference for BGISEQ-500 users to comprehensively understand DNBSEQ technology, solve sequencing problems and optimize run performance. These resources are available on our website http://seqBEACON.genomics.cn:443/home.html.

Abstract Background Ruili is a border city in southwest China along the heroin trafficking route. In recent decades, the city has witnessed increased in HIV transmission. The current study aims to explore the spatiotemporal trends in HIV prevalence identify and map the spatial variation and clustering of factors associated with HIV transmission through drug use and heterosexual contact transmissions at the village level from 1989 through 2016. Methods Geographic information system-based spatiotemporal analyses, including global and local spatial autocorrelation analyses and space-time scanning statistics, were applied to detect the location and extent of HIV/AIDS high-risk areas. Results Drug use and heterosexual contact were identified as the major transmission routes causing infection in Ruili. Results of global spatial analysis showed significant clustering throughout the city caused by transmission via drug use in the early phase of the epidemic and transmission via heterosexual contact in the late phase of the epidemic during the study period. Hotspots of transmission from drug use were randomly distributed throughout the city. However, the hotspots of transmission by heterosexual contact were located in the central area only around the Jiegao China-Myanmar land port. Space-time scanning showed that transmission from drug use clustered in the southwest area between 1989 and 1990, while transmission by heterosexual contact clustered in the central area between 2004 and 2014. Conclusions Heterosexual contact has become the dominant mode of transmission. Interventions should focus on highly clustered area where is around the Jiegao land port.

Objective: To investigate single-photon emission computed tomography/computed tomography (SPECT/CT) for assessing inflammation in the extraocular muscles (EOMs) and predicting the therapeutic efficacy of periocular glucocorticoid therapy (PGT) for Grave's ophthalmopathy (GO).Materials and Methods: A total of 412 eyes from 206 patients with GO referred for 99mTc-DTPA orbital SPECT/CT were enrolled. Fourteen age- and gender-matched healthy controls (28 eyes) were included. The thickness and uptake ratio (UR) of four EOMs were derived from SPECT/CT. Eighty-six eyes from patients with GO patients received PGT. Changes in SPECT/CT parameters were evaluated between the pre- and post-treatment.Results: 195 eyes and 217 eyes were classified as active and inactive stages by clinical activity score (CAS). Values of the thickness and UR of each EOM, Tmax, and Umax were all significantly higher in the active GO than in the inactive GO and controls (p < 0.01). Among the 86 eyes (48 GO patients) included in the efficacy analysis, 56 eyes and 30 eyes were classified as responders and non-responders. Values of thicknesses and UR of each EOM, the maximum thickness (Tmax), and the maximum UR (Umax) all dropped following PGT in the responders (p < 0.01). Logistic regression analysis identified the Umax as an independent predictor for the responders (p < 0.01). Moreover, the Umax demonstrated incremental predictive value over clinical characters and CAS, as evidenced by the improved area under the curve (0.85 vs. 0.78) and global chi-square (34.12 vs. 18.1).Conclusion:99mTc-DTPA SPECT/CT has the potential to assess inflammatory activity by detecting the involvement of EOMs in GO. Pre-treatment UR provides independent and incremental values for the prediction of PGT treatment response.

Summary: Designing effective carrier-selective contact is a prerequisite for high-efficiency crystalline silicon (c-Si) solar cells. Compared to doped silicon thin films, wide-band-gap transition metal oxides (TMOs) feature low parasitic absorption, but their carrier selectivity and passivation being poor leads to a mediocre cell efficiency. Herein, we introduce a NiOx/MoOx bilayer as an efficient hole-selective contact in c-Si solar cells. A power conversion efficiency (PCE) of 21.31% is achieved using NiOx/MoOx bilayer, outperforming cells with a single layer of NiOx or MoOx. Upon depositing NiOx on MoOx, interfacial reactions modify the stoichiometry and defect chemistry in both oxides, leading to a band alignment beneficial for hole selectivity. By inserting a SiOx tunneling layer on c-Si surface to further suppress recombination, we achieve a PCE of 21.60% (fill factor 83.34%). Our work highlights a promising approach to improve the performance of dopant-free c-Si solar cells by employing cost-effective TMOs as hole-selective contact.