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Objective: Type 2 diabetes (T2D) is a risk factor for cognitive impairment and cerebral small vessel disease (CSVD). The relation of metformin use and cognitive impairment or CSVD is not clear. The objective of this study was to investigate the cross-sectional effects of long-term use of metformin on total CSVD burden and cognitive function in patients with T2D.Methods: A total of 234 participants with T2D from the memory clinic in Hebei General Hospital were enrolled in this retrospective study. Duration of metformin use and dosage were recorded. Along with cerebral magnetic resonance imaging (MRI) examination, Mini-Mental State Examination (MMSE) was also performed to assess their cognitive status. We determined the validated total CSVD score (ranging from 0–4) by combining four markers of CSVD that were visually rated. We used binary logistic regression analysis, ordinal logistic regression analysis and mediation analysis to assess the relation of long-term use of metformin with CSVD burden and cognitive function.Results: Binary logistic regression analysis showed long-term use of metformin was associated with reducing the risk of cognitive impairment (OR: 0.446; 95% Confidence Interval (CI): 0.249 to 0.800; P = 0.007), after adjustment of potential confounders, such as total CSVD burden score, age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Ordinal logistic regression analysis suggested that long-term use of metformin was associated with alleviation of total CSVD burden score (OR: 0.583; 95% CI: 0.359 to 0.943; P = 0.027), after adjusting for age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Mediation analysis showed significant mediation by the presence of severe CSVD burden score for long-term use of metformin in relation to cognitive impairment.Conclusion: Long-term use of metformin was associated with lower rates of cognitive impairment and lower total CSVD burden score in patients with T2D. A proportion of the relation between long-term use of metformin and cognitive impairment may be attributable to alleviation of CSVD burden.

Small cell carcinoma (SCC)/neuroendocrine prostate cancer (NEPC) is a rare and highly aggressive subtype of prostate cancer associated with an AR(androgen receptor)-null phenotype and visceral metastases. This study presents a 44-year-old man originally diagnosed with metastatic hormone-sensitive prostatic adenocarcinoma. After 6-month androgen deprivation therapy (ADT) combined with docetaxel, the patient developed paraplegia. Laminectomy was performed, and a thoracic vertebral biopsy revealed neuroendocrine differentiation and mixed adenocarcinoma. The patient developed liver metastases and experienced stable disease for 4 months following etoposide combined with cisplatin and pembrolizumab. Seminal vesicle biopsy after chemotherapy revealed small-cell cancer. The prostate biopsy specimen also indicated pure SCC. We witnessed the dynamic evolution from pure adenocarcinoma to fully differentiated SCC, leading to obstruction and death. In addition, whole-exome sequencing was performed on both biopsy specimens of the thoracic vertebra at the beginning of castration resistance and that of seminal vesicle after multiple lines of treatment failure. Utilizing phylogenetic reconstruction, we observed that both samples shared a common ancestor clone harboring aberrations in the TP53, RB1, and NF2 genes. We also discovered that driver events in the private subclones of both samples, such as alterations in CDC27 and RUNX1, might have played a significant role in tumor progression or even neuroendocrine differentiation. Tumor biopsy and IHC assessment must be repeated at different stages of progression, because of intrapatient spatial and temporal heterogeneity of adenocarcinoma versus SCC/NEPC. Although, typical treatments including ADT, docetaxel, etoposide, cisplatin, and pembrolizumab provided temporary response, the patient still had a poor prognosis.

Trigonelline, one of the active compounds from Leonurus japonicus Houtt., has been proven to have pharmacological value in diabetes, the central nervous system and cardiovascular diseases. Recent studies have shown that it may also be beneficial in controlling inflammation. However, the mechanism of the antiallergic effects of trigonelline has not been well studied. As the key effector cells participating in the development of allergies, mast cells have been linked to the pathogenesis of asthma for ages. In this study, we demonstrated the inhibitory effect of trigonelline on activated bone marrow-derived mast cells (BMMCs) and verified its anti-inflammatory properties using an ovalbumin (OVA)-induced asthma model. Trigonelline suppressed BMMC degranulation and decreased the production of the cytokines, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) in a dose-dependent manner. The potent mechanism is mainly through the suppression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Trigonelline can alleviate pathological damage in lung tissue and reduce the levels of serum immunoglobulin E (IgE) and T helper 2 (Th2) cytokines. RNA-seq results revealed the HIF-1α to be a potential target for the allergic reaction. Taken together, our study demonstrated that trigonelline can inhibit allergic inflammation in vitro and in vivo, which may provide a basis for novel anti-inflammatory drug development.

Cells of all tissues in the human body share almost the exact same DNA sequence, but the epigenomic landscape can be drastically distinct. To improve our understanding of the epigenetic abnormalities in prostate-related diseases, it is important to use the epigenome of normal prostate as a reference. Although previous efforts have provided critical insights into the genetic and transcriptomic features of the normal prostate, a comprehensive epigenome map has been lacking. To address this need, we conducted a Roadmap Epigenomics legacy project integrating six histone marks (H3K4me1, H3K4me3, H3K9me3, H3K36me3, H3K27me3, and H3K27ac) with complete DNA methylome, transcriptome, and chromatin accessibility data to produce a comprehensive epigenome map of normal prostate tissue. Our epigenome map is composed of 18 chromatin states each with unique signatures of DNA methylation, chromatin accessibility, and gene expression. This map provides a high-resolution comprehensive annotation of regulatory regions of the prostate, including 105,593 enhancer and 70,481 promoter elements, which account for 5.3% of the genome. By comparing with other epigenomes, we identified 7,580 prostate-specific active enhancers associated with prostate development. Epigenomic annotation of GWAS SNPs associated with prostate cancers revealed that two out of nine SNPs within prostate enhancer regions destroyed putative androgen receptor (AR) binding motif. A notable SNP rs17694493, might decouple AR’s repressive effect on CDKN2B-AS1 and cell cycle regulation, thereby playing a causal role in predisposing cancer risk. The comprehensive epigenome map of the prostate is valuable for investigating prostate-related diseases.

Folium Hibisci Mutabilis, a new member of Chinese Pharmacopoeia, can treat some diseases induced by reactive oxygen species. The study prepared a lyophilized aqueous extract of Folium Hibisci Mutabilis (LAFHM). LAFHM was found to enrich eight flavonoids (i.e., quercetin, luteolin, hyperoside, isoquercitrin, rutin, kaempferol, tiliroside, and vitexin) by HPLC analysis. These flavonoids were further compared using antioxidant assays, where triliroside and vitexin always exhibited higher IC50 values than the others. In ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis, these flavonoids could basically give two characteristic m/z values (226 and 196) and their corresponding double m/z values (i.e., 602, 570, 926, 926, 570, 1186, and 862), when treated by 1,1-diphenyl-2-picryl-hydrazl radical (DPPH•). Finally, the coupling products of DPPH•-treated triliroside were investigated using computational chemistry. It was found that the –OH in para-coumaroyl moiety to have the lowest bond disassociation energy among all phenolic -OHs in the triliroside. In conclusion, Folium Hibisci Mutabilis contains the above eight antioxidant flavonoids. Despite of the different antioxidant levels, they can generally produce flavonoid-radical coupling product and flavonoid-flavonoid homodimer during antioxidant process. Especially, tiliroside uses para-coumaroyl as linker to construct a tiliroside-radical coupling product at the meta-carbon atom.

Introduction Although a considerable proportion of Asians in the USA experience depression, anxiety and poor sleep, these health issues have been underestimated due to the model minority myth about Asians, the stigma associated with mental illness, lower rates of treatment seeking and a shortage of culturally tailored mental health services. Indeed, despite emerging evidence of links between psychosocial risk factors, the gut microbiome and depression, anxiety and sleep quality, very few studies have examined how these factors are related in Chinese and Korean immigrants in the USA. The purpose of this pilot study was to address this issue by (a) testing the usability and feasibility of the study’s multilingual survey measures and biospecimen collection procedure among Chinese and Korean immigrants in the USA and (b) examining how stress, discrimination, acculturation and the gut microbiome are associated with depression, anxiety and sleep quality in this population.Method and analysis This is a cross-sectional pilot study among first and second generations of adult Chinese and Korean immigrants in the greater Atlanta area (Georgia, USA). We collected (a) gut microbiome samples and (b) data on psychosocial risk factors, depression, anxiety and sleep disturbance using validated, online surveys in English, Chinese and Korean. We aim to recruit 60 participants (30 Chinese, 30 Korean). We will profile participants’ gut microbiome using 16S rRNA V3-V4 sequencing data, which will be analysed by QIIME 2. Associations of the gut microbiome and psychosocial factors with depression, anxiety and sleep disturbance will be analysed using descriptive and inferential statistics, including linear regression.Ethics and dissemination This study has been approved by the Institutional Review Board at Emory University (IRB ID: STUDY00000935). Results will be made available to Chinese and Korean community members, the funder and other researchers and the broader scientific community.

Background: Pulmonary hypertension is one of the most common co-morbidities in infants with bronchopulmonary dysplasia (BPD), but its risk factors are unclear. The onset of pulmonary hypertension in BPD has been associated with poor morbidity- and mortality-related outcomes in infants. Two review and meta-analysis studies have evaluated the risk factors and outcomes associated with pulmonary hypertension in infants with BPD. However, the limitations in those studies and the publication of recent cohort studies warrant our up-to-date study. We designed a systematic review and meta-analysis to evaluate the risk factors and outcomes of pulmonary hypertension in infants with BPD.Objective: To systematically evaluate the risk factors and outcomes associated with pulmonary hypertension in infants with BPD.Methods: We systematically searched the academic literature according to the PRISMA guidelines across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE). We conducted random-effects meta-analyses to evaluate the pulmonary hypertension risk factors in infants with BPD. We also evaluated the overall morbidity- and mortality-related outcomes in infants with BPD and pulmonary hypertension.Results: We found 15 eligible studies (from the initial 963 of the search result) representing data from 2,156 infants with BPD (mean age, 25.8 ± 0.71 weeks). The overall methodological quality of the included studies was high. Our meta-analysis in infants with severe BPD revealed increased risks of pulmonary hypertension [Odds ratio (OR) 11.2], sepsis (OR, 2.05), pre-eclampsia (OR, 1.62), and oligohydramnios (OR, 1.38) of being small for gestational age (3.31). Moreover, a comparative analysis found medium-to-large effects of pulmonary hypertension on the total duration of hospital stay (Hedge's g, 0.50), the total duration of oxygen received (g, 0.93), the cognitive score (g, −1.5), and the overall mortality (g, 0.83) in infants with BPD.Conclusion: We identified several possible risk factors (i.e., severe BPD, sepsis, small for gestational age, pre-eclampsia) which promoted the onset of pulmonary hypertension in infants with BPD. Moreover, our review sheds light on the morbidity- and mortality-related outcomes associated with pulmonary hypertension in these infants. Our present findings are in line with the existing literature. The findings from this research will be useful in development of efficient risk-based screening system that determine the outcomes associated with pulmonary hypertension in infants with BPD.

Abstract Background Person-centered care is widely recognized as a gold standard and is based on a supportive psychosocial climate for both residents and staff in nursing homes. Residents and staff may have different perspectives as to whether the climate in which they interact is person-centered, perhaps due to their different expectations of the nursing home environment and the provision of care services. The aim of this study was to explore and compare resident and staff perspectives of person-centered climate in aged care nursing homes. Methods This is a descriptive cross-sectional study using a cluster random sampling method. The study collected data in 2016 from residents (n = 251) and nursing staff (n = 249) in 23 nursing homes using a Person-centered Climate Questionnaire-Patient version and Person-centered Climate-Staff version. T-tests for independent-samples were used to compare scores ranked by nursing staff and residents. Results The mean scores of ‘A climate of safety’ subscale and ‘A climate of everydayness’ subscale rated by residents were significantly lower than those rated by nursing staff. The mean scores of ‘A climate of hospitality’ rated by residents were very low among the three subscales, an indicator of the need to improve a more home-like environment for residents. Residents in larger size nursing homes showed a higher score of person-centered climate compared with their counterparts in small size nursing homes. Conclusions This study reveals that the perspectives and perceptions of person-centered climate differ between residents and nursing staff. Therefore, both resident and staff perspectives should be taken into account in attempting to improve person-centered climate for better care outcomes.

Several lines of evidence highlight the important application of human spermatogonial stem cells (SSCs) in translational medicine. The fate decisions of SSCs are mainly mediated by genetic and epigenetic factors. We have recently demonstrated that PAK1 regulates the proliferation, DNA synthesis, and early apoptosis of human SSCs through the PDK1/KDR/ZNF367 and ERK1/2 and AKT pathway. However, the underlying epigenetic mechanism of PAK1 in human SSCs remains unknown. In this study, we found that the level of miRNA-31-5p was elevated by PAK1 knockdown. CCK-8, PCNA, and 5-ethynyl-2′-deoxyuridine (EDU) assays revealed that miRNA-31-5p mimics inhibited cell proliferation and DNA synthesis of human SSCs. Annexin V/propidium iodide (PI) staining and flow cytometry showed that miRNA-31-5p increased the early and late apoptosis of human SSCs. Furthermore, JAZF1 was predicted and verified as a target of miRNA-31-5p, and the three-dimensional (3D) structure model of JAZF1 protein was illustrated. JAZF1 silencing led to a reduction of cell proliferation and DNA synthesis as well as an enhancement of the early and late apoptosis of human SSCs. Finally, miRNA-31-5p mimics decreased the level of cyclin A2 rather than cyclin D1 or cyclin E1, and JAZF1 knockdown led to the reduction of cyclin A2 in human SSCs. Collectively, miRNA-31-5p regulates the proliferation, DNA synthesis, and apoptosis of human SSCs by the PAK1-JAZF1-cyclin A2 pathway. This study thus offers a novel insight into the molecular mechanisms underlying the fate determinations of human SSCs and might provide novel targets for molecular therapy of male infertility. Keywords: miRNA-31-5p, human spermatogonial stem cells, proliferation, apoptosis, JAZF1, cyclin A2

Abstract Background Continuous cropping stress involves such factors as biological barriers, allelopathic autotoxicity, deterioration of soil physicochemical properties, and soil fertility imbalance and is regarded as a kind of comprehensive stress limiting soybean yield and quality. Genomic DNA methylation is an important regulatory mechanism for plants to resist various environmental stresses. Therefore, it is especially worthwhile to reveal genomic methylation characteristics under stress and clarify the relationship between DNA methylation status and continuous cropping stress adaptability in soybean. Results We generated a genome-wide map of cytosine methylation induced by this kind of comprehensive stress in a tolerant soybean variety (Kang Xian 2, KX2) and a sensitive variety (He Feng, HF55) using whole-genome bisulfite sequencing (WGBS) technology. The expression of DNA demethylase genes was detected using real-time quantitative PCR (qRT-PCR). The functions of differentially methylated genes (DMGs) involved in stress response in biochemical metabolism and genetic information transmission were further assessed based on Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results showed that genomic DNA demethylation was closely related to continuous cropping comprehensive stress adaptability in soybean, which was further verified by the increasing expression of DNA demethylases ROS1 and DML. The demethylation of mCpG and mCpHpG (mCpApG preferred) contexts was more critical, which mainly occurred in gene-regulatory regions at the whole-chromosome scale. Moreover, this kind of stress adaptability may be related to various stress responders generated through strengthened glucose catabolism and amino acid and fatty acid anabolism, as well as fidelity transmission of genetic information. Conclusions Genomic DNA demethylation was closely associated with continuous cropping comprehensive stress adaptability, highlighting the promising potential of screening continuous cropping-tolerant cultivars by DNA methylation index and further exploring the application of DNA demethylases in soybean breeding.

Abstract Background The morbidity of nephrolithiasis is 2–3 times higher in males than in females, suggesting that androgen plays a key role in nephrolithiasis. The death of renal tubular epithelial cells (TECs) is an important pathophysiological process contributing to the development of nephrolithiasis. Therefore, the aim of this study is to investigate whether androgen directly induces TECs apoptosis and necrosis and its underlying mechanisms in kidney stone formation. Materials and methods We compared serum testosterone level between male and female healthy volunteers and kidney stone patients. The in vivo nephrolithiasis model was established using glyoxylic acid, and calcium deposits were detected by van Kossa staining. In the in vitro study using mouse TECs (TCMK-1 cells) and human TECs (HK-2 cells), apoptosis, necrosis, and the expression of BH3-only protein Bcl-2-like 19 kDa-interacting protein 3 (BNIP3) were examined incubated with different doses of testosterone using flow cytometry. Levels of apoptosis-related proteins transfected with the BNIP3 siRNA were examined by western blotting. The mitochondrial potential (ΔΨm) was detected by JC-1 staining and flow cytometry. We monitored BNIP3 expression in the testosterone-induced TECs injury model after treatment with hypoxia inducible factor 1α (HIF-1α) and/or hypoxia inducible factor 2α (HIF-2α) inhibitors to determine the upstream protein regulating BNIP3 expression. Additionally, ChIP and luciferase assays were performed to confirm the interaction between HIF-1α and BNIP3. Results Both male and female patients have significantly higher testosterones compared with healthy volunteers. More calcium deposits in the medulla were detected in male mice compared to female and castrated male mice. Testosterone induced TECs apoptosis and necrosis and increased BNIP3 expression in a dose-dependent manner. Testosterone also increased Bax expression, decreased Bcl-2 expression and induced a loss of ΔΨm. This effect was reversed by BNIP3 knockdown. HIF-1α inhibition significantly decreased BNIP3 expression and protected TECs from testosterone-induced apoptosis and necrosis. HIF-2α inhibition, however, did not influence BNIP3 expression or TECs apoptosis or necrosis. Finally, HIF-1α interacted with the BNIP3 promoter region. Conclusion Based on these results, testosterone induced renal TECs death by activating the HIF-1α/BNIP3 pathway.

Squeezed state light is a fundamental resource for many quantum optics experiments. Important applications like quantum-enhanced magnetometer and quantum key distribution, require the squeezing level as high as possible. In balanced homodyne detection, the detector output is directly proportional to the noise of the squeezed beam. The detected quadrature is dependent on the relative phase between the squeezed beam and local oscillator. Here, we present a balanced homodyne detector (BHD) with independent phase control and noise detection branches. The independence between the phase control and noise detection branches is experimentally verified, the two branches are independently optimized according to the practical requirements. With the BHD, a bright squeezed light at 1550 nm with quantum noise reduction of 10.3 dB is directly detected. After stabilizing the relative phase between the squeezed states and local oscillator by the phase locking branch of the BHD, the fluctuation of the noise suppression is ±0.2 dB by 1-h testing time.

Previous studies established traffic demand equilibrium with an assumption that all the traffic information on road is easily accessed by the in-need traffic participants, which is not true in the real applications (due to data collections difficulty). The newly emerging smart portable devices (e.g., smart phones) generate massive on-site traffic data (speed, density, etc.), which stimulates us re-consider designing the traffic demand equilibrium. For the purpose of analyzing mobile internet service influence on traffic demand, we build up a Probit-based model with consideration of multiple traffic constraints (i.e., traveler type, actual travelling time, perceiving travelling time). The Monte Carlo method is introduced to simulating initial route selection probability distributions, and the Method of Successive Averages (MSA) is developed to help the Monte Carlo algorithm converge at optimal solution. We have implemented our model on typical traffic travelling scenario with very complex traffic network demands. The experimental results suggested that larger mobility service coverage can significantly reduce the overall traffic time in the free flow state, and the mobility service coverage rate ranging from 0.6 to 0.8 is supposed to provide minimum travelling time for the overall traffic network, while larger coverage rate at congested state may reduce the traffic network efficiency.

We propose the Weak Rescaled Pure Super Greedy Algorithm (WRPSGA) for approximation with respect to a dictionary D in Hilbert space. The WRPSGA is simpler than some popular greedy algorithms. We show that the convergence rate of the RPSGA on the closure of the convex hull of the μ-coherent dictionary D is optimal. Then, we design the Rescaled Pure Super Greedy Learning Algorithm (RPSGLA) for kernel-based supervised learning. We prove that the convergence rate of the RPSGLA can be arbitrarily close to the best rate O(m−1) under some mild assumptions.

Chemokines can induce chemotactic cell migration by interacting with G protein-coupled receptors to play a significant regulatory role in the development of cancer. CXC chemokine-12 (CXCL12) can specifically bind to CXC chemokine receptor 4 (CXCR4) and is closely associated with the progression of cancer via multiple signaling pathways. Over recent years, many CXCR4 antagonists have been tested in clinical trials; however, Plerixafor (AMD3100) is the only drug that has been approved for marketing thus far. In this review, we first summarize the mechanisms that mediate the physiological effects of the CXCL12/CXCR4 axis. Then, we describe the use of CXCL12/CXCR4 antagonists. Finally, we discuss the use of nano-based drug delivery systems that exert action on the CXCL12/CXCR4 biological axis.

The main aim of this study was to identify the bZIP family members in mung bean and explore their expression patterns under several abiotic stresses, with the overarching goal of elucidating their biological functions. Results identified 75 bZIP members in mung bean, which were unevenly distributed in the chromosomes (1–11), and all had a highly conserved bZIP domain. Phylogenetic analysis divided the members into 10 subgroups, with members in the same subgroup having similar structure and motif. The cis-acting elements in the promoter region revealed that most of the bZIP members might have the connection with abscisic acid, ethylene, and stress responsive elements. The transcriptome data demonstrated that bZIP members could respond to salt stress at different degrees in leaves, but the expression patterns could vary at different time points under stress. Differentially expressed genes (DEGs), such as VrbZIP12, VrbZIP37, and VrZIP45, were annotated into the plant hormone signal transduction pathway, which might be regulated the expression of abiotic stress-related gene (ABF). Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of bZIP members in roots and leaves under drought, alkali, and low-temperature stress. Results showed that bZIP members respond differently to diverse stresses, and their expression was tissue-specific, which suggests that they may have different regulatory mechanism in different tissues. Overall, this study will provide a reference for further research on the functions of bZIP members in mung bean.

IntroductionAsthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from Crocus sativus, shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model.MethodsOVA-induced asthma and PSA model were used to evaluate the effect of safranal in vivo. Lung tissues were collected for H&E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-α, and IFN-γ). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-α, and LTC4) and NF-κB and MAPKs signaling pathway were assessed.ResultsSafranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC4, IL-6, and TNF-α. Safranal inhibits NF-κB and MAPKs pathway protein phosphorylation and decreases NF-κB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC4 in serum.ConclusionsSafranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-κB pathways.

This study developed a comprehensive characterization method for the combined degradation effect of modified fluoroquinolones (FQs) photodegradation and microbial degradation. A combination of revised 3D-QSAR model, molecular docking, path simulation inference, pharmacokinetics, molecular dynamics (MD) simulation and toxicokinetics simulation was used to construct a systematic environment-friendly drug screening system. Five derivatives were screened with significantly improved combined degradation effect (over 20%) and functional characteristics and human health parameters through combined model verification, functional and human health risk assessment. The simulation path of photo- and microbial-degradation of gatifloxacin and new gatifloxacin molecules was derived, and the reaction energy barrier was also calculated. The ratio of the total rate-determining steps change rate of the decreased energy barrier (14.10%:26.30%) was consistent with the ratio of the increased degradation performance predicted by the model (22.87%:19.77%), demonstrating the reliability of revised 3D-QSAR model and it could be applied in molecular modification. MD and toxicokinetics simulation were used to predict the binding energy and aquatic toxicity between photo- and microbial-degradation products and the degradation enzymes, which further to screen the degradation pathways with low potential environmental risks. The findings will be helpful to screen environment-friendly drug and develop appropriate strategies for its risk management.

Cancer is a disease which frequently has a poor prognosis. Although multiple therapeutic strategies have been developed for various cancers, including chemotherapy, radiotherapy, and immunotherapy, resistance to these treatments frequently impedes the clinical outcomes. Besides the active resistance driven by genetic and epigenetic alterations in tumor cells, the tumor microenvironment (TME) has also been reported to be a crucial regulator in tumorigenesis, progression, and resistance. Here, we propose that the adaptive mechanisms of tumor resistance are closely connected with the TME rather than depending on non-cell-autonomous changes in response to clinical treatment. Although the comprehensive understanding of adaptive mechanisms driven by the TME need further investigation to fully elucidate the mechanisms of tumor therapeutic resistance, many clinical treatments targeting the TME have been successful. In this review, we report on recent advances concerning the molecular events and important factors involved in the TME, particularly focusing on the contributions of the TME to adaptive resistance, and provide insights into potential therapeutic methods or translational medicine targeting the TME to overcome resistance to therapy in clinical treatment.

Cancer-associated fibroblasts (CAFs) has been recognized as one cause of tumor resistance to immune checkpoint blockade therapy, but the underlying mechanisms still remain elusive. In the present study, a bone marrow-derived CAF (BMF) -rich tumor model is successfully established by subcutaneously mixed inoculation of BMFs and tumor cells into mice and the BMF-mixed tumor xenografts are demonstrated to be resistant to anti-PD-L1 antibody immunotherapy compared to the mere tumor xenografts. In vitro assays via the co-culture system of BMFs and tumor cells indicate that the co-cultured BMFs are induced to overexpress PD-L1, while there is no such a phenomenon in the co-cultured cancer cells. The further knock-out of PD-L1 in BMFs rescues the sensitivity of BMF-mixed tumor xenografts to PD-L1 blockade therapy. Mechanistically, via the microarray assay, we identify that the upregulation of PD-L1 in BMFs stimulated by cancer cells is medicated by the activation of the Wnt/β-catenin signaling pathway in BMFs. Moreover, the administration of Wnt/β-catenin signaling inhibitors, including XAV-939 and Wnt-C59, distinctly inhibits the upregulation of PD-L1 expression in the co-cultured BMFs. The further combination administration of XAV-939 significantly potentiates the therapeutic outcome of PD-L1 blockade therapy in BMF-mixed tumors. In summary, our study demonstrates that Wnt inhibition augments PD-L1 blockade efficacy by overcoming BMF-mediated immunotherapy resistance.

Road traffic safety is a social issue of widespread concern. It is important for traffic managers to understand the distribution patterns of road traffic accidents. To this end, this study examines the spatial and temporal patterns of road traffic accidents from both accident frequency and accident severity perspectives. Road traffic accident data from 2016 to 2018 in Harbin, China, were used for the analysis. First, the spatial localization of accidents was completed using geocoding, and the localized accident data were classified by season. Then, density analysis was performed both with and without considering road network density. The results of the density analysis showed that when road network density was considered, accidents were mainly distributed in urban centers, while accidents were more dispersed when road network density was not considered. Third, a cluster analysis considering accident severity found that low-severity accident clusters occurred mostly in urban centers. High-severity accident clusters were mostly present in suburban areas. Finally, the results of these two methods are shown by using the comap technique. Areas of the city with a high frequency and severity of crashes in each season were identified. This study will help traffic management to have a more visual and intuitive understanding of the urban traffic safety situation and to take targeted measures to improve it accordingly.

MicroRNAs (miRNAs) are essential factors in the reproductive process of poultry. Here, we found miR-302d is a potential differentiation and negative factor of chicken embryonic stem cells (ESCs) into spermatogonia stem cells (SSCs). The competition mechanism was carried out for the preliminary exploration to determine the relationship among miR-302d, lncRNA-341(interacting with miR-302d), and target gene TLE4. The results showed that lncRNA-341 can competitively bind to miR-302d to decrease the targeted binding of miR-302d and TLE4 which promotes the differentiation of chicken SSCs. Moreover, it is suggested that miR-302d may participate in the Wnt signaling pathway through TLE4.

We study the approximation capability of the orthogonal super greedy algorithm (OSGA) with respect to μ-coherent dictionaries in Hilbert spaces. We establish the Lebesgue-type inequalities for OSGA, which show that the OSGA provides an almost optimal approximation on the first [1/(18μs)] steps. Moreover, we improve the asymptotic constant in the Lebesgue-type inequality of OGA obtained by Livshitz E D.

Line-structured light three-dimensional (3D) measurement is apt for measuring the 3D profile of objects in complex industrial environments. The light-plane calibration, which is a crucial link, greatly affects the accuracy of measurement results. This paper proposes a novel calibration method for line-structured light 3D measurement based on a simple target, i.e., a single cylindrical target (SCT). First, the line-structured light intersects with the target to generate a light stripe. Meanwhile, the camera captures the calibration images, extracts the refined subpixel center points of the light stripe (RSCP) and detects the elliptic profiles of the two ends of the cylindrical target (EPCT). Second, two elliptical cones defined by the EPCT and the camera optical center are determined. Combining the two defined elliptical cones and the known radius of the SCT, we can uniquely solve the axis equation of the SCT. Finally, because the coordinates of RSCP in the camera coordinate system fulfill both the camera model and the cylindrical equation, these coordinates can be solved and used to obtain the optimal solution of the light-plane equation. The results of simulations and experiments verify that our proposed method has higher accuracy and effectiveness.

Ovarian follicle selection largely depends on the transition of granulosa cells from an undifferentiated to a fully differentiated state, which is accompanied by morphological and functional changes in follicles. The processes and transcriptional regulation of follicles during follicle selection are unclear; we thus used follicles from the prehierarchal to the hierarchal stage to investigate histology, reproductive endocrinology, and transcription. The morphology of follicles changed markedly during follicle selection. The numbers of large white, small yellow, and large yellow follicles (LWF, SYF, and LYF, respectively) were 11.83 ± 2.79, 6.83 ± 2.23, and 1.00, respectively, per ovary. LYF showed thicker granulosa cell layers than those of other prehierarchal follicles. Progesterone concentrations were significantly higher in LYF than that in LWF and SYF. In total, 16,823 genes were positively expressed in LWF, SYF, and LYF. Among follicle types, 1290 differentially expressed genes were enriched regarding cell differentiation, blood vessel morphogenesis, and response to steroid hormones. Candidate genes associated with follicle selection participated in the Wnt signaling pathway, steroid hormone biosynthesis, and the TGF-β signaling pathway. We produced insights into crucial morphological characteristics of transcriptional regulation in follicle development. Our results provide an important basis for revealing the mechanism of follicle selection and potential impact on the poultry industry.

Members of the Thaumarchaeota phylum play a key role in nitrogen cycling and are prevalent in a variety of environments including soil, sediment, and seawater. However, few studies have shown the presence of Thaumarchaeota in the terrestrial deep subsurface. Using high-throughput 16S rRNA gene sequencing, this study presents evidence for the high relative abundance of Thaumarchaeota in a biofilm sample collected from the well of Chinese Continental Scientific Drilling at a depth of 2000 m. Phylogenetic analysis showed a close relationship of these thaumarchaeotal sequences with known ammonia-oxidizing archaea (AOA) isolates, suggesting the presence of AOA in the deep metamorphic environment of eastern China which is believed to be oxic. Based on fluid geochemistry and FAProTax functional prediction, a pathway of nitrogen cycling is proposed. Firstly, heterotrophic nitrogen fixation is executed by diazotrophic bacteria coupled with methane oxidation. Then, ammonia is oxidized to nitrite by AOA, and nitrite is further oxidized to nitrate by bacteria within the phylum Nitrospirae. Denitrification and anaerobic ammonia oxidation occur slowly, leading to nitrate accumulation in the subsurface. With respect to biogeochemistry, the reaction between downward diffusing O2 and upward diffusing CH4 potentially fuels the ecosystem with a high relative abundance of Thaumarchaeota.

Previous studies have implicated the role of CD146 and its soluble form (sCD146) in the pathogenesis of inflammatory diseases. However, the association between CD146 and acute rejection in kidney transplant patients remains unexplored. In this study, fifty-six patients with biopsy-proved rejection or non-rejection and 11 stable allograft function patients were retrospectively analyzed. Soluble CD146 in plasma was detected in peripheral blood by enzyme linked immunosorbent assay (ELISA), and local CD146 expression in graft biopsy was detected by immunohistochemistry. We found that plasma soluble CD146 in acute rejection recipients was significantly higher than in stable patients without rejection, and the biopsy CD146 staining in the rejection group was higher than that of the non-rejection group. Multivariate analysis demonstrated soluble CD146 as an independent risk factor of acute rejection. The area under the receiver operating characteristic curve (AUC) of sCD146 for AR diagnosis was 0.895, and the optimal cut-off value was 75.64 ng/ml, with a sensitivity of 87.8% and a specificity of 80.8%, which was better than eGFR alone (P = 0.02496). Immunohistochemistry showed CD146 expression in glomeruli was positively correlated with the Banff-g score, and its expression in tubules also had a positive relationship with the Banff-t score. Therefore, soluble CD146 may be a potential biomarker of acute rejection. Increased CD146 expression in the endothelial or tubular epithelial cells may imply that endothelial/epithelial dysfunction is involved in the pathogenesis of immune injury.

BackgroundIn the Xuanwei region of China, lung cancer incidence and mortality are among the highest in China, attributed to severe air pollution generated by combustion of smoky coal. No study has yet comprehensively evaluated the prevalence of epidermal growth factor receptor (EGFR) mutation characteristics in patients with non-small cell lung cancer (NSCLC) in Xuanwei. This meta-analysis was designed to analyze the EGFR mutation pattern in NSCLC patients in Xuanwei region of Yunnan Province in China.MethodsElectronic databases were comprehensively searched and relevant literatures were retrieved. The odds ratio (OR) for EGFR mutations between Xuanwei region and non-Xuanwei region was calculated, and the absolute incidence of EGFR mutations in Xuanwei was pooled by mutation subtype.ResultsSeven studies involving 1,355 patients with NSCLC from Yunnan Province (442 in Xuanwei and 913 in other regions) were included. The EGFR mutation rate ranged between 30.19% and 55.56%. Higher uncommon EGFR mutations (OR: 5.69, 95%CI: 2.23–14.49, P

Efficient parking tends to be challenging in most large cities in China. Drivers often spend substantial amounts of time looking for parking lots while driving at low speeds, thereby resulting in interference with road traffic. This paper focuses on efficiently allocating parking spaces to the demanders. A double-objective model is proposed that considers both the utilizing rate and the walking distance. First, managers want to utilize parking resources fully. Therefore, they tend to prioritize the efficient distribution of parking spaces in response to parking demands. However, demanders typically choose parking spaces according to convenience. The second objective is the acceptable walking distance from the parking space to the destination. The particle swarm optimization (PSO) algorithm is used to solve this model. We collected parking demand and supply data in a central business district (CBD) of Harbin in China and evaluated the feasibility of the model. The results demonstrate that the proposed model increases the occupying rates of parking lots in residential zones while decreasing the walking distance. The shared use of parking spaces maximizes the utility and alleviates the shortage of parking spaces in downtown.

The optimization problem of the number of mirrors under energy efficiency (EE) maximization for vehicular visible light communication (VVLC) via mirror array-based intelligent reflecting surface (IRS) is investigated. Under considering that the formulated optimization problem is subject to the real and non-negative of the transmitted signal, the maximum power consumption satisfied luminous ability and eye safety, the minimum achievable rate, and the required bit error ratio (BER), EE is proved to be a unimodal function of the number of mirrors. Then, the binary search-conditional iteration (BSCI) algorithm is proposed for quickly finding the optimal number of mirrors with maximum EE. Numerical results demonstrate that fewer mirrors can obtain the maximum EE, and the computational complexity of the BSCI algorithm is reduced by 105 orders of magnitude, compared with the Bubble Sort method.

Spermatogonial stem cells (SSCs) have significant applications in reproductive and regenerative medicine. However, nothing is known about genes in mediating human SSCs. Here we have explored for the first time the function and mechanism of P21-activated kinase 1 (PAK1) in regulating the proliferation and apoptosis of the human SSC line. PAK1 level was upregulated by epidermal growth factor (EGF), but not glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF2). PAK1 promoted proliferation and DNA synthesis of the human SSC line, whereas PAK1 suppressed its apoptosis in vitro and in vivo. RNA sequencing identified that PDK1, ZNF367, and KDR levels were downregulated by PAK1 knockdown. Immunoprecipitation and Western blots demonstrated that PAK1 interacted with PDK1. PDK1 and KDR levels were decreased by ZNF367-small interfering RNAs (siRNAs). The proliferation of the human SSC line was reduced by PDK1-, KDR-, and ZNF367-siRNAs, whereas its apoptosis was enhanced by these siRNAs. The levels of phos-ERK1/2, phos-AKT, and cyclin A were decreased by PAK1-siRNAs. Tissue arrays showed that PAK1 level was low in non-obstructive azoospermia patients. Collectively, PAK1 was identified as the first molecule that controls proliferation and apoptosis of the human SSC line through PDK1/KDR/ZNF367 and the ERK1/2 and AKT pathways. This study provides data on novel gene regulation and networks underlying the fate of human SSCs, and it offers new molecular targets for human SSCs in translational medicine. Keywords: PAK1, human spermatogonial stem cells, proliferation, apoptosis, PDK1/KDR/ZNF367, ERK1/2 and AKT pathways

Human spermatogonial stem cells (SSCs) could have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. The fate determinations of human SSCs are mediated by epigenetic factors. However, nothing is known about the regulation of non-coding RNA on human SSCs. Here we have explored for the first time the expression, function, and target of miR-663a in human SSCs. MiR-663a was upregulated in human spermatogonia compared with pachytene spermatocytes, as indicated by microRNA microarray and real-time PCR. CCK-8 and 5-Ethynyl-2′-deoxyuridine (EDU) assays revealed that miR-663a stimulated cell proliferation and DNA synthesis of human SSCs. Annexin V and propidium iodide (PI) staining and flow cytometry demonstrated that miR-663a inhibited early and late apoptosis of human SSCs. Furthermore, NFIX was predicted and verified as a direct target of miR-663a. NFIX silencing led to an enhancement of cell proliferation and DNA synthesis and a reduction of the early apoptosis of human SSCs. NFIX silencing neutralized the influence of miR-663a inhibitor on the proliferation and apoptosis of human SSCs. Finally, both miR-663a mimics and NFIX silencing upregulated the levels of cell cycle regulators, including Cyclin A2, Cyclin B1, and Cyclin E1, whereas miR-663a inhibitor had an adverse effect. Knockdown of Cyclin A2, Cyclin B1, and Cyclin E1 led to the decrease in the proliferation of human SSCs. Collectively, miR-663a has been identified as the first microRNA that promotes the proliferation and DNA synthesis and suppresses the early apoptosis of human SSCs by targeting NFIX via cell cycle regulators Cyclin A2, Cyclin B1, and Cyclin E1. This study thus provides novel insights into the molecular mechanisms underlying human spermatogenesis, and it could offer novel targets for treating male infertility and other human diseases. Keywords: miRNA-663a, human spermatogonial stem cells, proliferation, apoptosis, NFIX, cell cycle proteins

Research and regulation of tree growth at molecular level is a new trend in the development of forest biotechnology. However, as the limitations of wood as a research material, it is difficult to operate and compare the growth cycle in the laboratory, which greatly hinders study of the molecular biology of forest trees. Arabidopsis thaliana is the most important model plant in botanical research and is an excellent material for plant molecular biology research. Recent studies have shown that herbaceous Arabidopsis can not only provide genetic resources for tree molecular breeding but also can be used as an auxiliary means of wood molecular biology research and even can be directly used as an experimental model for the study of the molecular mechanism of tree development. This paper mainly discusses the establishment process of the tree molecular gene system platform under the background of the Internet of Things and studies the molecular genome of Arabidopsis, combining the characteristics of the tree itself and using the diversity of the frequency of different bases in the gene fragment to cluster the tree molecular genome, which is a molecular biology research and provides an important way of thinking.

Human spermatogenesis includes three main stages, namely, the mitosis of spermatogonia, meiosis of spermatocytes, and spermiogenesis of spermatids, which are precisely regulated by epigenetic and genetic factors. Abnormality of epigenetic and genetic factors can result in aberrant spermatogenesis and eventual male infertility. However, epigenetic regulators in controlling each stage of normal and abnormal human spermatogenesis remain unknown. Here, we have revealed for the first time the distinct microRNA profiles in human spermatogonia, pachytene spermatocytes, and round spermatids between obstructive azoospermia (OA) patients and non-obstructive azoospermia (NOA) patients. Human spermatogonia, pachytene spermatocytes, and round spermatids from OA patients and NOA patients were isolated using STA-PUT velocity sedimentation and identified by numerous hallmarks for these cells. RNA deep sequencing showed that 396 microRNAs were differentially expressed in human spermatogonia between OA patients and NOA patients and 395 differentially expressed microRNAs were found in human pachytene spermatocytes between OA patients and NOA patients. Moreover, 378 microRNAs were differentially expressed in human round spermatids between OA patients and NOA patients. The differential expression of numerous microRNAs identified by RNA deep sequencing was verified by real-time PCR. Moreover, a number of novel targeting genes for microRNAs were predicted using various kinds of software and further verified by real-time PCR. This study thus sheds novel insights into epigenetic regulation of human normal spermatogenesis and the etiology of azoospermia, and it could offer new targets for molecular therapy to treat male infertility.

Tropospheric ozone is the only normal pollutant with a continuously increasing annual average concentration worldwide. In this study, data were monitored at the Nankai University Air Quality Research Supersite (NKAQRS) (38.99° N, 117.33° E) between 1 April, and 31 August from 2018 to 2020, 33 O3 episodes from 2018 to 2020 were analyzed to reveal the characteristics of O3, VOCs and OFP during O3 episodes and to evaluate the driving factors. The O3 episodes showed a decreasing trend in terms of pollution frequency, days, heavy pollution duration and peak concentration. Ethane, acetylene, cyclopentane, and methylcyclopentane were the major types in 2020, while 1-hexene was the main component in 2019. The main ozone-contributing species in 2020 were propene cyclopentane methylcyclopentane and ethylene. Alkenes were important contributors to ozone formation. Using generalized additive models (GAMs), the explanatory variables in the study are divided into environmental and meteorological factors, and 16 impact factors are selected as explanatory variables. We found that the influence of these meteorological factors on O3 pollution was nonlinear and impacted by the interaction between variables. O3 episodes were mainly driven by meteorological and precursor (NO) factors in 2018, while meteorological conditions (T), followed by precursor (NO2) were the driving factors in 2019 and 2020, suggesting that O3 episodes were mainly driven by meteorological conditions.

With the popularity of Android, malware detection and family classification have also become a research focus. Many excellent methods have been proposed by previous authors, but static and dynamic analyses inevitably require complex processes. A hybrid analysis method for detecting Android malware and classifying malware families is presented in this paper, and is partially optimized for multiple-feature data. For static analysis, we use permissions and intent as static features and use three feature selection methods to form a subset of three candidate features. Compared with various models, including k-nearest neighbors and random forest, random forest is the best, with a detection rate of 95.04%, while the chi-square test is the best feature selection method. After using feature selection to explore the critical static features contained in this dataset, we analyzed a subset of important features to gain more insight into the malware. In a dynamic analysis based on network traffic, unlike those that focus on a one-way flow of traffic and work on HTTP protocols and transport layer protocols, we focused on sessions and retained protocol layers. The Res7LSTM model is then used to further classify the malicious and partially benign samples detected in the static detection. The experimental results show that our approach can not only work with fewer static features and guarantee sufficient accuracy, but also improve the detection rate of Android malware family classification from 71.48% in previous work to 99% when cutting the traffic in terms of the sessions and protocols of all layers.

The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC–ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.

Forced expression of core cardiogenic transcription factors can directly reprogram fibroblasts to induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. This cardiac reprogramming approach provides a proof of concept for induced heart regeneration by converting a fibroblast fate to a cardiomyocyte fate. However, it remains elusive whether chamber-specific cardiomyocytes can be generated by cardiac reprogramming. Therefore, we assessed the ability of the cardiac reprogramming approach for chamber specification in vitro and in vivo. We found that in vivo cardiac reprogramming post-myocardial infarction exclusively induces a ventricular-like phenotype, while a major fraction of iCMs generated in vitro failed to determine their chamber identities. Our results suggest that in vivo cardiac reprogramming may have an inherent advantage of generating chamber-matched new cardiomyocytes as a potential heart regenerative approach.

The wide application of encryption technology has made traffic classification gradually become a major challenge in the field of network security. Traditional methods such as machine learning, which rely heavily on feature engineering and others, can no longer fully meet the needs of encrypted traffic classification. Therefore, we propose an Inception-LSTM(ICLSTM) traffic classification method in this paper to achieve encrypted traffic service identification. This method converts traffic data into common gray images, and then uses the constructed ICLSTM neural network to extract key features and perform effective traffic classification. To alleviate the problem of category imbalance, different weight parameters are set for each category separately in the training phase to make it more symmetrical for different categories of encrypted traffic, and the identification effect is more balanced and reasonable. The method is validated on the public ISCX 2016 dataset, and the results of five classification experiments show that the accuracy of the method exceeds 98% for both regular encrypted traffic service identification and VPN encrypted traffic service identification. At the same time, this deep learning-based classification method also greatly simplifies the difficulty of traffic feature extraction work.

With the rapid increase in the number of Android malware, the image-based analysis method has become an effective way to defend against symmetric encryption and confusing malware. At present, the existing Android malware bytecode image detection method, based on a convolution neural network (CNN), relies on a single DEX file feature and requires a large amount of computation. To solve these problems, we combine the visual features of the XML file with the data section of the DEX file for the first time, and propose a new Android malware detection model, based on a temporal convolution network (TCN). First, four gray-scale image datasets with four different combinations of texture features are created by combining XML files and DEX files. Then the image size is unified and input to the designed neural network with three different convolution methods for experimental validation. The experimental results show that adding XML files is beneficial for Android malware detection. The detection accuracy of the TCN model is 95.44%, precision is 95.45%, recall rate is 95.45%, and F1-Score is 95.44%. Compared with other methods based on the traditional CNN model or lightweight MobileNetV2 model, the method proposed in this paper, based on the TCN model, can effectively utilize bytecode image sequence features, improve the accuracy of detecting Android malware and reduce its computation.

Rutile nano-titanium dioxide (RNTD) characterized by loose particles with diameter in 20–50 nm has a very large surface area for adsorption of Tl, a typical trace metal that has severe toxicity. The increasing application of RNTD and widespread discharge of Tl-bearing effluents from various industrial activities would increase the risk of their co-exposure in aquatic environments. The adsorption behavior of Tl(I) (a prevalent form of Tl in nature) on RNTD was studied as a function of solution pH, temperature, and ion strength. Adsorption isotherms, kinetics, and thermodynamics for Tl(I) were also investigated. The adsorption of Tl(I) on RNTD started at very low pH values and increased abruptly, then maintained at high level with increasing pH >9. Uptake of Tl(I) was very fast on RNTD in the first 15 min then slowed down. The adsorption of Tl(I) on RNTD was an exothermic process; and the adsorption isotherm of Tl(I) followed the Langmuir model, with the maximum adsorption amount of 51.2 mg/g at room temperature. The kinetics of Tl adsorption can be described by a pseudo-second-order equation. FT-IR spectroscopy revealed that -OH and -TiOO-H play an important role in the adsorption. All these results indicate that RNTD has a fast adsorption rate and excellent adsorption amount for Tl(I), which can thus alter the transport, bioavailability and fate of Tl(I) in aqueous environment.

This study was designed to investigate the hemodynamic effect of rolipram, a phosphodiesterase type 4 (PDE4) inhibitor, in normal rat hearts both in vivo and in vitro and its underlying mechanism. The pressure-volume loop, isolated heart, and Ca2+ transients triggered by field stimulation or caffeine were used to analyze the hemodynamic mechanism of rolipram. The results demonstrated that rolipram (3 mg/kg, ip) significantly increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-systolic volume, end-diastolic volume, end-systolic pressure, heart rate, ejection fraction, peak rate of rise of left pressure (+dp/dtmax), the slopes of end-systolic pressure-volume relationship (slope of ESPVR) named as left ventricular end-systolic elastance, and reduced the slopes of end-diastolic pressure-volume relationship (slope of EDPVR). Meanwhile, the systolic blood pressure, diastolic blood pressure, and pulse pressure were significantly enhanced by rolipram. Also, rolipram deviated normal ventricular-arterial coupling without changing the arterial elastance. Furthermore, rolipram (0.1, 1, 10 μM) also exerted positive inotropic effect in isolated rat hearts by increasing the left ventricular development pressure, and +dp/dtmax in non-paced and paced modes. Rolipram (10 μM) increased the SERCA2a activity, Ca2+ content, and Ca2+ leak rate without changing diastolic Ca2+ level. Rolipram had significant positive inotropic effect with less effect on peripheral vascular elastance and its underlying mechanism was mediated by increasing SERCA2a activity. PDE4 inhibition by rolipram resulted in a positive inotropic effect and might serve as a target for developing agents for the treatment of heart failure in clinical settings.

More frequent trade transactions between countries exacerbate the environmental pollution, especially chemical products which are rather sensitive to environmental impact since they have rich varieties and high complexity of chemical reaction process. It is therefore necessary for us to analyze and study the national trade transfers and environmental pollution of so many chemicals. Based on the complex network theory, this paper throws light on the national trade transfer properties of organic chemicals. Given this, it is analyzed what impact they play on environmental pollution. A network map of environmental pollution impact is thereby built, providing the clues to the production and trading of organic chemicals in China.

Minerals provide physical niches and supply nutrients or serve as electron donors/acceptors for microorganism survival and growth, and thus minerals and microbes co-evolved. Yet, little is known about how sediment minerals impact microbial community assembly in hot springs and to what extent mineralogical composition influences microbial community composition and diversity. Here the influences of minerals on thermophiles in Tengchong hot springs were revealed by network analysis of field samples, as well as in-situ microcosm experiments with minerals. A molecular ecological network was constructed based on high throughput sequencing data of 16S rRNA gene, with a combination of water geochemistry and sedimentary mineralogical compositions. Six modules were identified and this highly modular network structure represents the microbial preference to different abiotic factors, consequently resulting in niche partitioning in sedimentary communities in hot springs. Diverse mineralogical compositions generated special niches for microbial species. Subsequently, the in-situ microcosm experiments with four minerals (aragonite, albite, K-feldspar, and quartz) and spring water were conducted in a silicate-hosted alkaline spring (i.e., Gmq) and a carbonate-hosted neutral hot spring (i.e., Gxs) for 70 days. Different microbial preferences were observed among different mineral types (carbonate versus silicate). Aragonite microcosms in Gmq spring enriched archaeal genera Sulfophobococcus and Aeropyrum within the order Desulfurococcales by comparison with both in-situ water and silicate microcosms. Sulfophobococcus was also accumulated in Gxs aragonite microcosms, but the contribution to overall dissimilarity is much lower than that in Gmq spring. Besides, Caldimicrobium was a bacterial genus enriched in Gxs aragonite microcosms, in contrast to in-situ water and silicate microcosms, whereas Candidatus Kryptobacter and Thermus were more abundant in silicate microcosms. The differences in microbial accumulations among different mineral types in the same spring implied that mineral chemistry may exert extra deterministic selective pressure in drawing certain species from the bulk water communities, in addition to stochastic absorption on mineral surface. Taken together, our results highlight the special niche partitioning determined by mineralogical compositions and further confirm that minerals could be used as “fishing bait” to enrich certain rare microbial species.

Mesozoic porphyritic rocks from the Zijinshan area, southwestern Fujian Province, China, are andesitic to rhyolitic in composition. The whole-rock SiO2 contents of these rocks are between 62.5% and 78.1%. Magmatic zircon from the Mesozoic porphyritic rocks was determined via secondary-ionization mass spectrometry (SIMS) for the U-Pb age and Hf and O isotopes. The zircon U-Pb ages could be mainly divided into three age groups: Group 1: ~138.8 Ma; Group 2: 109.2~107.4 Ma; and Group 3: 99.7~98.2 Ma. The εHf(t) and δ18O values of the porphyritic zircons showed that the porphyritic rocks in Group 2 were more affected by mantle-derived magma. Combined with previous research results, the medium-acidic magmatism in the southwestern Fujian Province can be divided into eight periods: Paleoproterozoic, Mesoproterozoic, Middle Neoproterozoic, Silurian to Lower Devonian, Permian to Triassic, Middle Jurassic to early Lower Cretaceous, late Lower Cretaceous, and late Lower Cretaceous to early Upper Cretaceous. The Paleoproterozoic crust was the predominant magmatic source for the subsequent Mesoproterozoic to Jurassic magmatism, but the only melts that were closely related to mineralization were derived from partial melting of the Mesoproterozoic crust and a more depleted upper mantle.

The present study established an efficient genome editing approach for the construction of stable transgenic cell lines of the domestic chicken (Gallus gallus domesticus). Our objectives were to facilitate the breeding of high-yield, high-quality chicken strains, and to investigate gene function in chicken stem cells. Three guide RNA (gRNAs) were designed to knockout the C2EIP gene, and knockout efficiency was evaluated in DF-1 chicken fibroblasts and chicken ESCs using the luciferase single-strand annealing (SSA) recombination assay, T7 endonuclease I (T7EI) assay, and TA clone sequencing. In addition, the polyethylenimine-encapsulated Cas9/gRNA plasmid was injected into fresh fertilized eggs. At 4.5 d later, frozen sections of the embryos were prepared, and knockout efficiency was evaluated by the T7EI assay. SSA assay results showed that luciferase activity of the vector expressing gRNA-3 was double that of the control. Results of the T7EI assay and TA clone sequencing indicated that Cas9/gRNA vector-mediated gene knockdown efficiency was approximately 27% in both DF-1 cells and ESCs. The CRISPR/Cas9 vector was also expressed in chicken embryos, resulting in gene knockdown in three of the 20 embryos (gene knockdown efficiency 15%). Taken together, our results indicate that the CRISPR/Cas9 system can mediate stable gene knockdown at the cell and embryo levels in domestic chickens.

In order to study the effect of initial defects on fatigue crack propagation law, a test method to identify fatigue crack propagation rate and path based on load waveform variation was presented, and a new test device was designed to apply fatigue pulsation loads to multiple wires for bridge cables simultaneously in this paper. To simplify the corrosion defect formation process, a machine-cut notch was used to describe the initial defect on the steel wire surface. Firstly, fatigue crack propagation tests were conducted on the surface notched steel wire specimens. By using crack front marking technique, the “beach-like patterns” visible to the naked eyes on the cross sections of the steel wires were formed, and the process of fatigue crack propagation can be tracked and reproduced. Then Autodesk Computer Aided Design (AutoCAD) software was used to describe the morphology of “beach-like patterns” and accurately measure the depth and width of cracks. Finally, the influence of initial defect morphology on fatigue crack propagation rate was investigated according to the relationship between fatigue cracks depth and cyclic loading numbers. The results show that the test device designed in this paper can effectively realize the synchronous fatigue crack propagation test of multiple wires, and significantly shorten the fatigue test period. By observing and analyzing the change of load waveform, the moment of fatigue crack propagation can be directly and accurately determined. The larger the depth, the smaller the width and the sharper the morphology of initial defect, the faster the crack propagation rate and the shorter the life of notched wire specimens under the combined action of fatigue loads and corrosive medium.

The durability problem in high-strength steel wire used for bridge cable is becoming more and more severe due to chlorine salt erosion, with the primary corrosion morphology of steel wire surfaces being pit corrosion. To simplify the pitting formation process, a machine-cut notch was used to represent a corrosion pit caused by electrochemical non-uniformity, and then the fatigue performance and corrosion fatigue performance of steel wire with initial defects were studied experimentally. A new type of test device was designed to carry out synchronous pulsating fatigue loading on multiple wires. A series of S-N curves of steel wire with initial defects under various loading conditions was obtained, and the effects of the concentration and pH value of the corrosive solution, and the shape and dimension of the initial defect on the fatigue corrosion performance of steel wire for bridge cables were investigated. The results show that the test device designed in this paper can effectively perform the life test under the combined action of corrosive medium and fatigue load, and can considerably shorten the duration of the fatigue test. Under the combined action of corrosive medium and fatigue load, the life of steel wire with an initial defect is significantly lower than that without consideration of the corrosion effect. The corrosion fatigue performance of steel wire decreases with the increase of acidity of the corrosive solution, rather than the increase of solution concentration. The life of steel wire with a narrow deep notch is much lower than that with a wide shallow notch. The stress concentration leads to a sharp reduction in wire life.

Highland barley starch (HBS), as a carbohydrate shell material with excellent performance in microcapsule applications, has rarely been reported. In the present study, three different microcapsules (CEO-SWSM, CEO-PM, and CEO-UM) were synthesized successfully via saturated aqueous solution method, molecular inclusion method and ultrasonic method, respectively, using HBS as shell material coupled with cinnamon essential oil (CEO) as the core material. The potential of HBS as a new shell material and the influence of synthetic methods on the performance of microcapsules, encapsulation efficiency (EE), yield, and release rate of CEO-SWSM, CEO-PM, and CEO-UM were determined, respectively. The results confirmed that CEO-PM had the most excellent EE (88.2%), yield (79.1%), as well as lowest release rate (11.5%, after 25 days of storage). Moreover, different kinetic models were applied to fit the release process of these three kinds of microcapsules: CEO-SWSM, CEO-PM, and CEO-UM had the uppermost R-squared value in the Higuchi model, the zero-order model, and the first-level model, respectively. Over all, this work put forward a novel perspective for the improved encapsulation effect of perishable core materials (e.g., essential oil) for the food industry.