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Abstract Background The incidence of mental health problems among medical graduate students is much higher than among students of other disciplines. This can have adverse consequences for the medical students themselves as well as their future patients. This study aims to understand the pressures faced by Chinese medical students and the current status of mental health education. It also propose recommendations for the current situation and prospects for the future. Method The authors conducted in-depth semi-structured interviews with 22 master’s students from five medical schools during November 2023. All interview sessions were recorded and transcribed verbatim. The transcriptions were analyzed using the Colaizzi’s seven-step method. Result Three main themes were extracted from the students’ statements: sources of psychological stress, ways to cope with stress, and perspectives on mental health education. The study showed that current mental health education in China is mostly in the form of printed mental health education manuals and mental health lectures, and there is no active tiered intervention for students at different levels. It is suggested that reforms should be made to shift to a model where the school proactively identifies problems and intervenes based on feedback. Conclusion This study reveals the widespread psychological stress and shortcomings in current education methods. To address these challenges, institutions should develop tailored interventions, including tiered support systems, open dialogue promotion, and resilience training. Future research should focus on evaluating innovative interventions’ effectiveness, ultimately fostering a supportive environment that enhances students’ success and contributes to a healthier healthcare workforce.

Human beings are living longer than ever before and aging is accompanied by an increased incidence of motor deficits, including those associated with the neurodegenerative conditions, Parkinson's disease (PD) and Huntington's disease (HD). However, the biological correlates underlying this epidemiological finding, especially the functional basis at the synapse level, have been elusive. This study reveals that motor skill performance examined via rotarod, beam walking and pole tests is impaired in aged mice. This study, via electrophysiology recordings, further identifies an aging-related reduction in the efficacy of inhibitory synaptic transmission onto dorsolateral striatum (DLS) indirect-pathway medium spiny neurons (iMSNs), i.e., a disinhibition effect on DLS iMSNs. In addition, pharmacologically enhancing the activity of DLS iMSNs by infusing an adenosine A2A receptor (A2AR) agonist, which presumably mimics the disinhibition effect, impairs motor skill performance in young mice, simulating the behavior in aged naïve mice. Conversely, pharmacologically suppressing the activity of DLS iMSNs by infusing an A2AR antagonist, in order to offset the disinhibition effect, restores motor skill performance in aged mice, mimicking the behavior in young naïve mice. In conclusion, this study identifies a functional inhibitory synaptic plasticity in DLS iMSNs that likely contributes to the aging-related motor skill deficits, which would potentially serve as a striatal synaptic basis underlying age being a prominent risk factor for neurodegenerative motor deficits.

Abstract Background The timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged

Abstract Background D-type cyclins (CYCD) regulate the cell cycle G1/S transition and are thus closely involved in cell cycle progression. However, little is known about their functions in rice. Results We identified 14 CYCD genes in the rice genome and confirmed the presence of characteristic cyclin domains in each. The expression of the OsCYCD genes in different tissues was investigated. Most OsCYCD genes were expressed at least in one of the analyzed tissues, with varying degrees of expression. Ten OsCYCD proteins could interact with both retinoblastoma-related protein (RBR) and A-type cyclin-dependent kinases (CDKA) forming holistic complexes, while OsCYCD3;1, OsCYCD6;1, and OsCYCD7;1 bound only one component, and OsCYCD4;2 bound to neither protein. Interestingly, all OsCYCD genes except OsCYCD7;1, were able to induce tobacco pavement cells to re-enter mitosis with different efficiencies. Transgenic rice plants overexpressing OsCYCD2;2, OsCYCD6;1, and OsCYCD7;1 (which induced cell division in tobacco with high-, low-, and zero-efficiency, respectively) were created. Higher levels of cell division were observed in both the stomatal lineage and epidermal cells of the OsCYCD2;2- and OsCYCD6;1-overexpressing plants, with lower levels seen in OsCYCD7;1-overexpressing plants. Conclusions The distinct expression patterns and varying effects on the cell cycle suggest different functions for the various OsCYCD proteins. Our findings will enhance understanding of the CYCD family in rice and provide a preliminary foundation for the future functional verification of these genes.

PurposeThis study investigated whether RNA-Seq-based endometrial receptivity test (rsERT)—which provides precision for the optimal hour of the window of implantation (WOI)—can improve clinical outcomes of frozen embryo transfer (FET) cycles in patients with a history of repeated implantation failure (RIF).MethodsPatients with a history of RIF who received at least one autologous high-quality blastocyst during the subsequent FET cycle were retrospectively enrolled and divided into two groups: rsERT and FET, comprising patients who underwent rsERT-guided pET (n=115) and standard FET without rsERT (n=272), respectively.ResultsIn the rsERT group, 39.1% (45/115) of patients were receptive. rsERT patients showed a higher probability of achieving both positive human chorionic gonadotropin (63.5% vs. 51.5%, P=0.03) and clinical pregnancy (54.8% vs. 38.6%, P=0.003) rates. In subgroup analysis, rsERT patients with non-receptive results had higher clinical pregnancy rates than patients undergoing FET (58.6% vs. 38.6%, P=0.003). rsERT patients with receptive results guided by rsERT with a precise WOI time had higher, although non-significant, clinical pregnancy rates (48.9% vs. 38.6%, P=0.192) than patients who underwent standard-time FET.ConclusionHourly precise rsERT can significantly improve the probability of achieving clinical pregnancy in patients with RIF, especially in those with non-receptive rsERT results.

IntroductionBacterial resistance presents a major challenge to both the ecological environment and human well-being, with persistence playing a key role. Multiple studies were recently undertaken to examine the factors influencing the formation of persisters and the underlying process, with a primary focus on Gram-negative bacteria and Staphylococcus aureus (Gram-positive bacteria). Enterococcus faecalis (E. faecalis) is capable of causing a variety of infectious diseases, but there have been few studies of E. faecalis persisters. Previous studies have shown that the sex pheromone cCF10 secreted by E. faecalis induces conjugative plasmid transfer. However, whether the pheromone cCF10 regulates the persistence of E. faecalis has not been investigated.MethodsAs a result, we investigated the effect and potential molecular mechanism of pheromone cCF10 in regulating the formation of persisters in E. faecalis OG1RF using a persistent bacteria model.Results and discussionThe metabolically active E. faecalis OG1RF reached a persistence state and temporarily tolerated lethal antibiotic concentrations after 8 h of levofloxacin hydrochloride (20 mg/mL) exposure, exhibiting a persistence rate of 0.109 %. During the growth of E. faecalis OG1RF, biofilm formation was a critical factor contributing to antibiotic persistence, whereas 10 ng/mL cCF10 blocked persister cell formation. Notably, cCF10 mediated the antibiotic persistence of E. faecalis OG1RF via regulating metabolic activity rather than suppressing biofilm formation. The addition of cCF10 stimulated the Opp system and entered bacterial cells, inhibiting (p)ppGpp accumulation, thus maintaining the metabolically active state of bacteria and reducing persister cell generation. These findings offer valuable insights into the formation, as well as the control mechanism of E. faecalis persisters.

Abstract Background Due to the chronic nature of HIV, mental health has become a critical concern in people living with HIV (PLWHIV). However, little knowledge exists about the association between fear of progression (FoP) and medical coping modes (MCMs) in PLWHIV in China. Methods A cohort of 303 PLWHIV were consecutively enrolled and their demographic, clinical and psychological information was collected. The Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Social Support Rating Scale (SSRS), Internalized HIV Stigma Scale (IHSS) and MCMs Questionnaire were utilized. Results Of the participants, 215 PLWHIV were classified into the low-level FoP group, and 88 were grouped into the high-level FoP group based on their FoP-Q-SF scores, according to the criteria for the classification of dysfunctional FoP in cancer patients. The high-level group had a higher proportion of acquired immunodeficiency syndrome (AIDS) stage (P = 0.005), lower education levels (P = 0.027) and lower income levels (P = 0.031). Additionally, the high-level group had lower scores in social support (P

Abstract Curiosity, or novelty seeking, is a fundamental mechanism motivating animals to explore and exploit environments to improve survival, and is also positively associated with cognitive, intrapersonal and interpersonal well-being in humans. However, curiosity declines as humans age, and the decline even positively predicts the extent of cognitive decline in Alzheimer’s disease patients. Therefore, determining the underlying mechanism, which is currently unknown, is an urgent task for the present aging society that is growing at an unprecedented rate. This study finds that seeking behaviors for both social and inanimate novelties are compromised in aged mice, suggesting that the aging-related decline in curiosity and novelty-seeking is a biological process. This study further identifies an aging-related reduction in the activity (manifesting as a reduction in spontaneous firing) of dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Finally, this study establishes that this reduction in activity causally underlies the aging-related decline in novelty-seeking behaviors. This study potentially provides an interventional strategy for maintaining high curiosity in the aged population, i.e., compensating for the reduced activity of VTA/SNc dopaminergic neurons, enabling the aged population to cope more smoothly with the present growing aging society, physically, cognitively and socioeconomically.

In the field of image segmentation, there are still some technical problems, such as the segmentation accuracy of the image with intensity inhomogeneity is not high enough. Level set method has the advantages of solid theoretical foundation and stable algorithm for segmentation of small sample data, so far it has played a significant role in image segmentation. In this paper, with the level set method for the research framework, we present a new approach to segment noise and weak boundary images that is supported by an adaptive velocity correction function. Based on the properties analysis of noise and edge information, this correction function is replaced the original constant to largely improve the segmentation accuracy. In addition, on the basis of some theoretical analysis, we use the edge stop function constructed by entropy to effectively improve the accuracy of image segmentation. Finally, a large number of challenging image experiments show that the proposed segmentation model performs better than other classical models in segmentation accuracy.

PurposeThe family residence structure serves as a crucial pathway through which the family environment influences adolescents’ development.MethodsDrawing on nationally representative data, this study employs multiple linear regression models and propensity score matching to examine the impact of various family residence structures on adolescents’ non-cognitive abilities. Causal identification is achieved through propensity score matching, while robustness is assessed using methods such as augmented inverse probability weighting and placebo tests. Heterogeneity analysis is conducted based on gender and household registration, aiming to explore the mechanisms by which family residence structure affects adolescents’ non-cognitive abilities.ResultsThe findings indicate that compared to two-parent co-residence households, three-generation co-residence families have significantly positive effects on emotional stability, conscientiousness, and agreeableness among adolescents. In contrast, skip-generation coresidence families exhibit significant negative effects on emotional stability and agreeableness in adolescents. Further investigation into the underlying mechanisms reveals that parental involvement and family socioeconomic status within three-generation co-residence families positively influence adolescents’ non-cognitive abilities.ConclusionThis study highlights the importance of considering grandparents’ role in adolescent growth and advocates for policy recommendations focusing on enhancing non-cognitive abilities in adolescents from skip-generation co-residence families.

Abstract A lack of stability in the expression of Bacillus thuringiensis genes (CRY) and the dialaninophosphate resistance gene (BAR) in transgenic rice plants can lead to the loss of important characters. The genetic stability of transgenic expression in high-generation lines is thus critically important for ensuring the success of molecular breeding efforts. Here, we studied the genetic stability of resistance to insect pests and herbicides in transgenic rice lines at the molecular and phenotypic levels in a pesticide-free environment. Southern blot analysis, real-time polymerase chain reaction, and enzyme-linked immunosorbent assays revealed high stability in the copy numbers and expression levels of CRY1C, CRY2A, and BAR in transgenic lines across different generations, and gene expression levels were highly correlated with protein expression levels. The insecticide resistance of the transgenic rice lines was high. The larval mortality of Chilo suppressalis was 50.25% to 68.36% higher in transgenic lines than in non-transgenic control lines. Percent dead hearts and percent white spikelets were 16.66% to 22.15% and 27.07% to 33.47% lower in transgenic lines than in non-transgenic control lines, respectively. The herbicide resistance of the transgenic rice lines was also high. The bud length and root length ranged were 2.53 cm to 4.20 cm and 0.28 cm to 0.73 cm higher in transgenic lines than in non-transgenic control lines in the budding stage, respectively. Following application of the herbicide Basta, the chlorophyll content of the transgenic lines began to recover 2 d later in the seedling and tillering stages and 3 d later in the booting and heading stages, by contrast, the chlorophyll content of the non-transgenic lines did not recover and continued to decrease. These findings revealed high genetic stability of the resistance to insect pests and herbicides across several generations of transgenic rice regardless of the genetic background.

Abstract Background Phytochromes are important photoreceptors in plants, and play essential roles in photomorphogenesis. The functions of PhyA and PhyB in plants have been fully analyzed, while those of PhyC in plant are not well understood. Results A rice mutant, late heading date 3 (lhd3), was characterized, and the gene LHD3 was identified with a map-based cloning strategy. LHD3 encodes phytochrome C in rice. Animo acid substitution in OsphyC disrupted its interaction with OsphyB or itself, restraining functional forms of homodimer or heterodimer formation. Compared with wild-type plants, the lhd3 mutant exhibited delayed flowering under both LD (long-day) and SD (short-day) conditions, and delayed flowering time was positively associated with the day length via the Ehd1 pathway. In addition, lhd3 showed a pale-green-leaf phenotype and a slower chlorophyll synthesis rate during the greening process. The transcription patterns of many key genes involved in photoperiod-mediated flowering and chlorophyll synthesis were altered in lhd3. Conclusion The dimerization of OsPhyC is important for its functions in the regulation of chlorophyll synthesis and heading. Our findings will facilitate efforts to further elucidate the function and mechanism of OsphyC and during light signal transduction in rice.

BackgroundThe fertility of female kidney transplant recipients is increasing with the progression of transplant management. This article aims to evaluate the clinical prognosis of mothers and newborns for post-kidney transplant couples.MethodsFrom January 2019 to April 2022, a total of four couples, all kidney transplant recipients, were successfully prepared for pregnancy after a rigorous preconception evaluation, including three cases of natural conception and one case of in vitro fertilization. Data regarding the mother and newborn, including general clinical condition and laboratory results, were recorded and assessed throughout the pregnancy and up until 12 months after delivery.ResultsThe mean conception age of the mothers was 34.8 years (30–38 years), and the mean interval between renal transplantation and pregnancy was 6.6 years (3.7–8.7 years). All deliveries were by cesarean section and took place without incident. There were three premature births (

Pervious concrete (PC) pavements can effectively reduce surface runoff, but it will be clogged with time and its service life will be affected. In this study, based on three groups of PC specimens with different aggregate gradations optimized by previous experiments, the pavement-clogging simulation test is carried out using the two-way coupling of the particle flow code with computational fluid dynamics (PFC-CFD). The results show that when the gradation of aggregates in the pervious pavement is different, the volume fraction of clogging material in the pavement and the time when the volume fraction of the clogging material reaches the maximum are also different. It is related to the zigzag degree and size of the pore in the pervious pavement. The smaller the particle size of coarse aggregate in the pervious pavement, the easier it is to be clogged, and the discontinuous graded coarse aggregate has a good shielding effect on the clogging material. Different clogging material gradations have different effects on the clogging of pervious pavements. According to the aforementioned research results, researchers can select different mix ratios of anti-clogging PC according to different areas of use. The law obtained from the experiment can provide a reference for further study of the double-layer pervious pavement structure design.

Abstract Background Computational prediction of the interaction between drugs and protein targets is very important for the new drug discovery, as the experimental determination of drug-target interaction (DTI) is expensive and time-consuming. However, different protein targets are with very different numbers of interactions. Specifically, most interactions focus on only a few targets. As a result, targets with larger numbers of interactions could own enough positive samples for predicting their interactions but the positive samples for targets with smaller numbers of interactions could be not enough. Only using a classification strategy may not be able to deal with the above two cases at the same time. To overcome the above problem, in this paper, a drug-target interaction prediction method based on multiple classification strategies (MCSDTI) is proposed. In MCSDTI, targets are firstly divided into two parts according to the number of interactions of the targets, where one part contains targets with smaller numbers of interactions (TWSNI) and another part contains targets with larger numbers of interactions (TWLNI). And then different classification strategies are respectively designed for TWSNI and TWLNI to predict the interaction. Furthermore, TWSNI and TWLNI are evaluated independently, which can overcome the problem that result could be mainly determined by targets with large numbers of interactions when all targets are evaluated together. Results We propose a new drug-target interaction (MCSDTI) prediction method, which uses multiple classification strategies. MCSDTI is tested on five DTI datasets, such as nuclear receptors (NR), ion channels (IC), G protein coupled receptors (GPCR), enzymes (E), and drug bank (DB). Experiments show that the AUCs of our method are respectively 3.31%, 1.27%, 2.02%, 2.02% and 1.04% higher than that of the second best methods on NR, IC, GPCR and E for TWLNI; And AUCs of our method are respectively 1.00%, 3.20% and 2.70% higher than the second best methods on NR, IC, and E for TWSNI. Conclusion MCSDTI is a competitive method compared to the previous methods for all target parts on most datasets, which administrates that different classification strategies for different target parts is an effective way to improve the effectiveness of DTI prediction.

BackgroundAcute rejection is a determinant of prognosis following kidney transplantation. It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment.MethodsGene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway—T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene.ResultsA total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples.ConclusionsOur study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis.

In plants, MAP65 preferentially cross-links the anti-parallel microtubules (MTs) and plays an important role for cytokinesis. However, the functions of MAP65 isoforms in rice (Oryza sativa. L) are largely unknown. Here, we identified two MAP65-3 homologs in rice, OsMAP65-3.1 and OsMAP65-3.2. We found that both OsMAP65-3.1 and OsMAP65-3.2 were similar in dimerization and location to AtMAP65-3, and the expression of either rice genes driven by the AtMAP65-3 promoter suppressed the cytokinesis failure and growth defect of atmap65-3. However, OsMAP65-3.1 with native promoter also recovered the atmap65-3, but OsMAP65-3.2 with its own promoter had no effects. OsMAP65-3.1 but not OsMAP65-3.2 was actively expressed in tissues enriched with dividing cells. R1R2R3-Myb (MYB3R) transcription factors directly bound to the OsMAP65-3.1 promoter but not that of OsMAP65-3.2. Furthermore, osmap65-3.2 had no obvious phenotype, while either osmap65-3.1 or osmap65-3.1(+/-) was lethal. The eminent MTs around the daughter nuclei and cytokinesis defects were frequently observed in OsMAP65-3.1-defective plants. Taken together, our findings suggest that OsMAP65-3.1, rather than OsMAP65-3.2, plays essential roles in rice cytokinesis resulting from their differential expression which were passably directly regulated by OsMYB3Rs.

Abstract Background Protein–protein interactions (PPIs) are the core of protein function, which provide an effective means to understand the function at cell level. Identification of PPIs is the crucial foundation of predicting drug-target interactions. Although traditional biological experiments of identifying PPIs are becoming available, these experiments remain to be extremely time-consuming and expensive. Therefore, various computational models have been introduced to identify PPIs. In protein-protein interaction network (PPIN), Hub protein, as a highly connected node, can coordinate PPIs and play biological functions. Detecting hot regions on Hub protein interaction interfaces is an issue worthy of discussing. Methods Two clustering methods, LCSD and RCNOIK are used to detect the hot regions on Hub protein interaction interfaces in this paper. In order to improve the efficiency of K-means clustering algorithm, the best k value is selected by calculating the distance square sum and the average silhouette coefficients. Then, the optimization of residue coordination number strategy is used to calculate the average coordination number. In addition, the pair potentials and relative ASA (PPRA) strategy is also used to optimize the predicted results. Results DataHub dataset and PartyHub dataset were used to train two clustering models respectively. Experiments show that LCSD and RCNOIK have the same coverage with Hub protein datasets, and RCNOIK is slightly higher than LCSD in Precision. The predicted hot regions are closer to the standard hot regions. Conclusions This paper optimizes two clustering methods based on PPRA strategy. Compared our methods for hot regions prediction against the well-known approaches, our improved methods have the higher reliability and are effective for predicting hot regions on Hub protein interaction interfaces.

An increasing trend of research on microplastics (MPs) pollution in soil requires plenty of accurate data on MPs occurrence in soil samples. Efficient and economical methods of obtaining MP data are in development, especially for film MPs. We focused on MPs originating from agricultural mulching films (AMF) and presented an approach that can separate MPs in batches and identify them quickly. It mainly includes separation by ultrasonic cleaning and centrifugation, digestion of organic matter, and an AMF-MPs identification model. Adding olive oil or n-hexane to saturated sodium chloride constituted the best combination of separation solutions. Controlled experiments proved that the optimized methods improved the efficiency of this approach. The AMF-MPs identification model provides specific characteristics of MPs and can identify MPs efficiently. Evaluation results showed that the mean MP recovery rate reached 95%. The practical application demonstrated that this approach could conduct MPs analysis in soil samples in batches with less time and low cost.

Porous MgAl2O4 ceramics were prepared via in-situ decomposition pore-forming (ISDP) technique using Al(OH)3 and magnesite as raw materials. The influence of Al(OH)3 particle size (0–44 µm, 44–88 µm, 88–100 µm, 100–150 µm) on the microstructures and strengths of porous spinel ceramics were investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectrometer (EDS). The bimodal distributions were observed among all the pore size distributions of the porous spinel ceramics. The small pores existed inside the particles and the big pores existed between the particles. When the Al(OH)3 particle size decreased from 100–150 µm to 0–44 µm, the peak of large pores shifted towards left while intensity of the peak of small pores decreased. Simultaneously, the neck-bonds formed between particles grew significantly, which resulted in the increase of compressive strength from 1.4 to 10.8 MPa. The optimized product is the sample with the Al(OH)3 particle size of 0–44 µm, which has a high apparent porosity (55.2%), a high compressive strength (10.8 MPa) and a relatively homogeneous pore size distribution.

Abstract Background Long control region (LCR) of human papillomavirus (HPV) has shown multiple functions on regulating viral transcription. The variations of LCR related to different lineages/sub-lineages have been found to affect viral persistence and cervical cancer progression differently. In this study, we focused on gene polymorphism of HPV16/18/58 LCR to assess the effect variations caused on transcription factor binding sites (TFBS) and provided more data for further study of LCR in Southwest China. Methods LCR of HPV16/18/58 were amplified and sequenced to do polymorphic and phylogenetic anlysis. Sequences of each type were aligned with the reference sequence by MEGA 6.0 to identify SNPs. Neighbor-joining phylogenetic trees were constructed using MEGA 6.0. Transcription factor binding sites were predicted by JASPAR database. Results The prevalence of these three HPVs ranked as HPV16 (12.8%) > HPV58 (12.6%) > HPV18 (3.5%) in Chengdu, Southwest China. 59 SNPs were identified in HPV16-LCR, 18 of them were novel mutations. 30 SNP were found in HPV18-LCR, 8 of them were novel. 55 SNPs were detected in HPV58-LCR, 18 of them were novel. Also, an insertion (CTTGTCAGTTTC) was detected in HPV58-LCR between position 7279 and 7280. As shown in the neighbor-joining phylogenetic trees, most isolates of HPV16/18/58 were clustered into lineage A. In addition, one isolate of HPV16 was classified into lineage C and 3 isolates of HPV58 were classified as lineage B. JASPAR results suggested that TFBS were potentially influenced by 7/6 mutations on LCR of HPV16/18. The insertion and 5 mutations were shown effects in LCR of HPV58. Conclusion This study provides more data for understanding the relation among LCR mutations, lineages and carcinogenesis. It also helps performing further study to demonstrate biological function of LCR and find potential marker for diagnosis and therapy.

The relationship between the microstructure and properties of laser-clad Cu-Fe alloys with different W contents was investigated. As the content of W increased, the size of the Fe core free in the Fe-rich region first decreased and then increased. In addition, almost all the W condensed in the Fe-rich region. The calculations verified that the Fe core in the molten pool was mainly driven by the Marangoni motion, and the phase field was used to simulate the nucleation and diffusion of the Fe cores inside the molten pool, revealing the formation process of the Fe-rich region. The addition of W was also beneficial in improving the wear resistance of the Cu-Fe alloy. When the W content was increased to 30%, the coefficient of friction of the alloy was reduced by 13%.

The propagation of pollutants between regions has become a noticeable factor affecting air pollution. Given the complicated propagation relationship, most of the existing works lack an effective perception mechanism of geographic correlations and time-varying features, which is crucial in exploring and understanding the propagation mechanism by integrating empirical knowledge and data inherent characteristics. In this paper, we abstract the complicated propagation relationship between regions as a dynamic network, and introduce visual analytics techniques to explore the spatiotemporal multivariate patterns of air pollution propagation. A particle tracking based model is first proposed to construct pollution propagation networks under multi-source factors. It combines numerical simulation and data characteristics simultaneously, and detects active pollution source areas based on long-term transport relationships and temporal correlations. Based on it, we extract propagation patterns and analyze the temporal evolution of diachronic propagation networks. Moreover, we design an interactive system to achieve an in-depth analysis of air pollution issues. Through elaborate multi-level glyphs and linkage views, the system facilitates users to perceive and explore propagation mechanism in spatiotemporal multivariate information, and compare propagation patterns from global and local perspectives. We present several case studies to demonstrate the usefulness of our work in air pollution propagation analysis.

The extent of molecular diversity and differentially expressed proteins (DEPs) in transgenic lines provide valuable information to understand the phenotypic performance of transgenic crops compared with their parents. Here, we compared the differences in the phenotypic variation of twelve agronomic and end-use quality traits, the extent of microsatellite diversity, and DEPs of a recurrent parent line with three transgenic rice restorer lines carrying either CRY1C gene on chromosome 11 or CRY2A gene on chromosome 12 or both genes. The three transgenic lines had significantly smaller stem borer infestation than the recurrent parent without showing significant differences among most agronomic traits, yield components, and end-use quality traits. Using 512 microsatellite markers, the three transgenic lines inherited 2.9–4.3% of the Minghui 63 donor genome and 96.3–97.1% of the CH891 recurrent parent genome. As compared with the recurrent parent, the number of upregulated and down-regulated proteins in the three transgenic lines varied from 169 to 239 and from 131 to 199, respectively. Most DEPs were associated with the secondary metabolites biosynthesis transport and catabolism, carbohydrate transport and metabolism, post-translational modification, and signal transduction mechanisms. Although several differentially expressed proteins were observed between transgenic rice and its recurrent parent, the differences may not have been associated with grain yield and most other phenotypic traits in transgenic rice.

In this study, a two-step method was used to realize the liquefaction of waste sawdust under atmospheric pressure, and to achieve a high liquefaction rate. Specifically, waste sawdust was pretreated with NaOH, followed by liquefaction using phenol. The relative optimum condition for alkali–heat pretreatment was a 1:1 mass ratio of NaOH to sawdust at 140 °C. The reaction parameters including the mass ratio of phenol to pretreated sawdust, liquefaction temperature, and liquefaction time were optimized by response surface methodology. The optimal conditions for phenol liquefaction of pretreated sawdust were a 4.21 mass ratio of phenol to sawdust, a liquefaction temperature of 173.58 °C, and a liquefaction time of 2.24 h, resulting in corresponding liquefied residues of 6.35%. The liquefaction rate reached 93.65%. Finally, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) were used to analyze untreated waste sawdust, pretreated sawdust, liquefied residues, and liquefied liquid. SEM results showed that the alkali–heat pretreatment and liquefaction reactions destroyed the intact, dense, and homogeneous sample structures. FT-IR results showed that liquefied residues contain aromatic compounds with different substituents, including mainly lignin and its derivatives, while the liquefied liquid contains a large number of aromatic phenolic compounds. XRD showed that alkali–heat pretreatment and phenol liquefaction destroyed most of the crystalline regions, greatly reduced the crystallinity and changed the crystal type of cellulose in the sawdust.

Breast cancer is one of the most common cancers diagnosed in women. For preventive diagnosis, feature selection is an essential step to construct the breast cancer classifier. The features of a real breast cancer dataset are usually composed of discrete and continuous ones. Also, the Area Under the Curve (AUC) of the receiver operating characteristic receives more attention in such a medical field. The existing research work is insufficient to take into account both the hybrid trait of the features and the specific classification objective. We have proposed a wrapper method, i.e., a integrated framework in which Bayesian classifiers are embedded for the feature selection of breast cancer datasets. To deal with both the discrete features and the continuous features, we adopt the naive approach for the discrete features but the kernel probability density estimation for the continuous ones, respectively, which leads to feature-type-aware hybrid Bayesian classifiers. All the classifiers are fed with different feature subsets and evaluated by their AUC metrics as the fitness indexes. Thus, with the genetic algorithm, we can obtain a near optimal feature subset, which yields a good AUC metric with its corresponding classifiers. Moreover, the one-class F-score is used to help enhance the convergence of the algorithm. Experiments are done both with the continuous Wisconsin diagnostic breast cancer dataset and the real breast cancer dataset for Chinese women. The results prove that the proposed wrapper is feasible, accurate and efficient, compared with the related genetic algorithm based approaches.

The key to drug discovery is the identification of a target and a corresponding drug compound. Effective identification of drug–target interactions facilitates the development of drug discovery. In this paper, drug similarity and target similarity are considered, and graphical representations are used to extract internal structural information and intermolecular interaction information about drugs and targets. First, drug similarity and target similarity are fused using the similarity network fusion (SNF) method. Then, the graph isomorphic network (GIN) is used to extract the features with information about the internal structure of drug molecules. For target proteins, feature extraction is carried out using TextCNN to efficiently capture the features of target protein sequences. Three different divisions (CVD, CVP, CVT) are used on the standard dataset, and experiments are carried out separately to validate the performance of the model for drug–target interaction prediction. The experimental results show that our method achieves better results on AUC and AUPR. The docking results also show the superiority of the proposed model in predicting drug–target interactions.

BackgroundMany studies have shown that NAFLD is indeed closely related to the occurrence of colon tumors. The aim of this study was to further establish an assessment for the risk associated with NAFLD and the site-specificity of colon tumors.MethodsWe searched the PubMed, Embase, Cochrane, and Scopus databases published from January 1, 1981, to December 15, 2019, assessing the risk of colorectal neoplasms in patients with NAFLD. The primary outcome measure was the incidence of site-specific risk of colorectal neoplasms in patients with NAFLD reported as ORs which pooled under a random-effects model and calculated via Mantel-Haenszel weighting. The study is registered with PROSPERO, number CRD42020162118.Results11 articles (12,081 participants) were included in this meta-analysis. After heterogeneity removed, the overall risk-value pooled for right colon tumors(OR = 1.60,95% CI 1.27-2.01,I2 = 58%,P = 0.02)was higher than the left(OR = 1.39,95% CI 1.11-1.73,I2 = 59%,P = 0.02).However, this outcome was unclear when considering gender differences (Male&Right:OR = 1.05; Male&Left:OR = 1.26; Female&Right: OR = 1.17; Female&Left:OR = 1.17).The incidence of right colon tumors(Asian&Right:OR = 1.56)was obviously higher in Asians with NAFLD than the left (Asian&Left:OR = 1.23),while the risk relevance was similar and moderately associated with an increased risk of incident double-sided colorectal tumors in Europeans (European&Right:OR = 1.47; European&Left:OR = 1.41). The outcome of pathological morphology includes: the advanced adenoma OR = 1.82;the tubular adenoma OR = 1.24;the serrated adenoma OR = 2.16.ConclusionsNAFLD is associated with a high risk of colon tumors, especially in regard to tumors of the right colon, which are more prevalent in Asian populations.

Leaf senescence is one of the most common factors that affects the growth and yield of rice. Although numerous genes affecting leaf senescence have been identified, few involved in cuticular wax synthesis have been described for rice premature leaf senescence. Here, we cloned and characterized Premature Leaf Senescence 4 (PLS4) in rice (Oryza sativa), which encodes a putative 3-oxoacyl-reductase in the fatty acid biosynthetic pathway. Subcellular localization of OsPLS4 was observed in the chloroplast. A single nucleotide substitution in OsPLS4 reduced leaf cuticular wax, and the expression levels of most wax biosynthesis-associated genes were downregulated. TEM showed chloroplast development were defective in the pls4 mutant. Further investigation revealed that the chlorophyll (Chl) content was reduced in the pls4 mutant compared with the WT and that the photosynthesis rate was lower, which caused ROS dramatic accumulation at the heading stage. These results confirmed premature leaf senescence in pls4 plants. Cold treatment indicated that the mutant was more sensitive than the WT was to cold stress. Together, all the above results indicate that the OsPLS4 mutation affects cuticular wax biosynthesis and chloroplast development in rice, causing reduced cuticular wax and premature leaf senescence.

Abstract Background Exercise-based cardiac rehabilitation is a beneficial therapy for patients with chronic heart failure. The delivery of exercise-based cardiac rehabilitation should adopt an evidence-based approach, as well as be culturally appropriate and sensitive to individual needs and preferences. The Baduanjin Eight-Silken-Movements with Self-efficacy Building for Heart Failure (BESMILE-HF) program is the first to apply a traditional Chinese exercise, Baduanjin, as the core component in an exercise-based cardiac rehabilitation program. This trial aims to assess the efficacy, safety, and acceptability of the addition of the BESMILE-HF program to usual medications for patients with chronic heart failure. Methods/design The BESMILE-HF study is a mixed-design study. It includes a two-group, parallel, randomized controlled trial with 200 chronic heart failure patients, as well as a qualitative component. Patients will be randomized into either an intervention group receiving the 12-week BESMILE-HF program plus usual medications, or a control group receiving only usual medications. The primary outcomes are peak oxygen consumption assessed using a cardiopulmonary exercise test, and disease-specific quality of life using the Minnesota Living with Heart Failure Questionnaire. The secondary outcomes are: exercise performance, exercise self-efficacy, general quality of life, dyspnea and fatigue, depression, cardiac function, prognostic and inflammatory indicator levels, hospitalization, use of medications, and major adverse cardiac events. Assessments will be carried out at baseline, and at the 4th week, 8th week, and 12th week. The qualitative component will include a semi-structure interview describing patients’ experiences with the intervention. Discussion This study can provide evidence for how to deliver a contextually adapted exercise-based cardiac rehabilitation program with the potential to be scaled up throughout China. Trial registration ClinicalTrials.gov, ID: NCT03180320. Registered on 2 June 2017.

Offshore drilling rigs are the foundation of oil and gas exploitation in water areas. Their spatial and temporal distribution, state attributes and other information directly reflect the exploitation level of regional oil and gas resources. Therefore, it is very important to build an automatic detecting method for offshore drilling rigs with good performance to accurately capture the temporal and spatial distribution and state of oil and gas exploitation activities. At present, there are two main groups of methods for offshore drilling rigs: invariant feature-based methods and nighttime firelight-based methods. Methods based on invariant location are more subjective in terms of their parameter settings and require intensive computation. Nighttime light-based methods are largely unable to identify offshore drilling rigs without associated waste gas ignition. Furthermore, multiple offshore drilling rigs in close proximity to one another cannot be effectively distinguished with low spatial resolution imagery. To address these shortcomings, we propose a new method for the automatic identification of offshore drilling rigs based on Landsat-7 ETM+ images from 2018 to 2019, taking the Caspian Sea as the research area. We build a nominal annual cloud and cloud shadow-free Normalized Difference Water Index (NDWI) composite by designing an optimal NDWI compositing method based of the influence of cloud and cloud shadow on the NDWI values of water, bare land (island) and offshore drilling rigs. The classification of these objects is simultaneously done during the compositing process, with the following rules: water body (Max_NDWI > 0.55), bare land (island) (Min_NDWI < −0.05) and offshore drilling rig (0 < Mean_NDWI < 0.4). A threshold segmentation and postprocessing were carried out to further refine the results. Using this method, 497 offshore platforms were automatically identified using a nominal annual cloud and cloud shadow-free NDWI composite image and Google Earth Engine. Validation using Sentinel-2 Multispectral Imager (MSI) and Google Earth images demonstrated that the correct rate of offshore drilling rig detection in the Caspian Sea is 90.2%, the missing judgment rate is 5.3% and the wrong judgment rate is 4.5%, proving the performance of the proposed method. This method can be used to identify offshore drilling rigs within a large water surface area relatively quickly, which is of great significance for exploring the exploitation status of offshore oil and gas resources. It can also be extended to finer spatial resolution optical remote sensing images; thus small-size drilling rigs can be effectively detected.

Previous studies have indicated that the monocyte chemo-attractant protein 1 (MCP-1), also referred to as C-C motif chemokine ligand 2 (CCL2), plays a significant role in the pathogenesis of sepsis, and this study investigated the clinical relevance of two MCP-1 gene polymorphisms on sepsis onset and progression. The Multiplex SNaPshot genotyping method was used to detect MCP-1 gene polymorphisms in the Chinese Han population (403 sepsis patients and 400 controls). MCP-1 mRNA expression levels were measured using real-time quantitative PCR, and enzyme-linked immunosorbent assays were used to analyze MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1β) plasma concentrations. The rs1024611 polymorphism analysis showed lower frequencies of minor homozygous genotype (AA) and allele (A) in sepsis patients compared to the healthy controls (19.4% vs. 31.5%, P = 0.0001 and 45.9% vs. 54.8%, P = 0.0004, respectively). And the frequencies of GG genotype and G allele were lower in sepsis patients compared to the controls (19.6% vs. 31.3%, P = 0.0002 and 46.0% vs. 54.5%, P = 0.0007, respectively). The rs1024611 AG/GG and rs2857656 GC/CC genotypes were both overrepresented in patients with severe sepsis (both P = 0.0005) and septic shock (P = 0.010 and P = 0.015, respectively) compared to the patients with mild sepsis. Moreover, among sepsis patients, the rs1024611 AG/GG and rs2857656 GC/CC carriers exhibited significant increases in expression levels of MCP-1 (P = 0.025), TNF-α (P = 0.034) and IL-6 (P = 0.043) compared with the rs1024611 AA or rs2857656 GG carriers. This study provides valuable clinical evidence that the MCP-1/CCL2 polymorphisms rs1024611 and rs2857656 are associated with sepsis susceptibility and development. We conclude that MCP-1/CCL2 plays a significant role in the pathogenesis of sepsis, which has potentially important therapeutic implications.

BACKGROUND: Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration. METHODS AND FINDINGS: The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium. CONCLUSIONS: This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.