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Abstract Groundwater of Luohe Formation is the main water source for industrial and agricultural and residential use in Binchang mining area, which is one of the key elements to water conservation coal mining. However, few studies are available to document the enrichment characteristics and influence of underground coal mining on groundwater for the Luohe Formation. This study evaluates the changes of groundwater levels and spring flow caused by mining activities to explore the influence mechanism of coal mining on groundwater by comparatively analysing existing mining data and survey data combined with a series of mapping methods. The results show that the aquifer of Luohe Formation are gradually thinning south-eastwards, disappeared at the mining boundary. In the vertical direction, the lithological structure is distinct, due to alternative sedimentation of meandering river facies and braided river facies. According to the yielding property, the aquifer is divided into three sections, namely, strong water-rich section, medium water-rich section, and weak water-rich section, which are located in northwest and central part, southwest, and the rest part of the mining area, respectively. Mining of Tingnan Coal Mine since 2004 has caused a 3.16 to 194.87 meters drop in groundwater level of Luohe Formation. Until 2015, 70.10% of the mining area undergoes a groundwater level drop larger than 10.00 meters. Another influence of underground mining is that the total flow from 34 springs in 8 southern coal mines of the area has decreased by 286.48 L/s with a rate of decrease at 46.95% from 2007 to 2017. The areas that groundwater level falls or spring flow declines are manly located in the mine gob areas. Results also indicate that the ratio of the height of water conducted fracture zone to the mining height in Binchang mining area is between 16.85 and 27.92. This may increase ground water flow in vertical direction, causing a water level in the aquifer system to drop and ultimately decreasing the flow from the springs. The research results will provide data and theoretical support for the protection of groundwater resources and water conservation coal mining of Luohe Formation in Binchang mining area.

The main purpose of this study was to analyze the effect of coal mining on the springs in the Yushenfu mining area of China. The results of two springs and hydrological surveys conducted in 1994 and 2015 were compared to study the occurrence and evolution of springs before and after large-scale mining. The mechanism of spring evolution and ecological effects of domain evolution were analyzed by combined groundwater monitoring and evaluation of coal mining intensity. The results show that the maximum amount of single water inflow of spring with sand infiltration recharge was more than 10 L/s, the total amount of single water inflow of spring with mixed infiltration recharge was the highest, and the ecological effect of spring with loess infiltration recharge was the most significant. In the study area, 2580 springs (group) were distributed with a total flow of 4998.9428 L/s before 1994 and 376 residual springs (group) were present with a total flow of 996.392 L/s in 2015. Large-scale mining decreased the regional groundwater level, thus decreasing the amount of spring water. The high intensity of mining decreased the number of springs (group) and area of water and wetland in the study area. This directly affected the watershed ecology; the ecological degradation was significant.

Abstract Perennial ryegrass (Lolium perenne) is a widely cultivated forage and turf grass species. Salt stress can severely damage the growth of grass plants. The genome-wide molecular mechanisms of salt tolerance have not been well understood in perennial grass species. In this study, the salt sensitive genotype P1 (PI265351, Chile) and the salt tolerant genotype P2 (PI368892, Algeria) of perennial ryegrass were subjected to 200 mM NaCl, and transcriptomics and metabolomics analyses were performed. A total of 5,728 differentially expressed genes (DEGs) were identified through pairwise comparisons. Antioxidant enzyme encoding genes (LpSOD1, LpCAT1), ion channel gene LpCaC1 and transcription factors (LpERFs, LpHSF1 and LpMYB1) were significantly upregulated in P2, suggesting their involvement in regulating expression of salt-responsive genes for salt tolerance. Functional analysis of DEGs revealed that biosynthesis of secondary metabolites, carbohydrate metabolism and signal transduction were the main pathways in response to salt stress. Weighted gene co-expression network analysis (WGCNA) based on RNA-Seq data showed that membrane transport and ABC transporters were significantly correlated with salt tolerance-related traits. The combined transcriptomics and metabolomics analysis demonstrated that the phenylpropanoid biosynthesis pathway was a major secondary metabolic pathway in the salt response of perennial ryegrass. Especially, the tolerant genotype P2 had greater amounts of upregulated phenylpropanoids, flavonoids and anthocyanins and higher expressions of relevant genes in the pathway than the sensitive genotype P1, indicating a role of phenylpropanoid biosynthesis for perennial ryegrass to adapt to salt stress. The results provided insights into the molecular mechanisms of perennial ryegrass adaptation to salinity and laid a base for genetic improvement of salt tolerance in perennial grass species.

Abstract Topologically associating domains (TADs) are essential units of genome architecture, influencing transcriptional regulation and diseases. Despite numerous methods proposed for TAD identification, it remains challenging due to complex background and nested TAD structures. We introduce HTAD, a human-in-the-loop TAD caller that combines machine learning with human supervision to achieve high accuracy. HTAD begins with feature extraction for potential TAD border pairs, followed by an interactive labeling process through active learning. Performance assessments using public curation and synthetic datasets demonstrate HTAD’s superiority over other state-of-the-art methods and reveal highly hierarchical TAD structures, offering a human-in-the-loop solution for detecting complex genomic patterns.

ObjectiveThis study aims to elucidate the relationship between postoperative monocyte count and gastric cancer prognosis. We introduce a standardized monocyte ratio (MMR) to predict postoperative survival rates in gastric cancer patients effectively.MethodsA test cohort was created to develop and evaluate the pre- and postoperative MMR as a mortality predictor in gastric cancer patients. We used Kaplan-Meier survival analysis, complemented by univariate and multivariate analyses. The predictive utility of MMR was assessed via time-dependent ROC curves and decision-curve analysis.ResultsThe sample distributions in both cohorts were similar. The MMR showed high predictive value and significant clinical benefits in 1, 3, and 5-year overall survival (OS) assessments. These findings enhance understanding of prognosis and aid in developing more precise treatment plans.ConclusionsMMR is confirmed as an independent factor in predicting overall survival in gastric cancer patients, proving to be a reliable and cost-effective prognostic indicator.

Background: Inflammatory breast cancer (IBC) is an aggressive and rare phenotype of breast cancer, which has a poor prognosis. Thus, it is necessary to establish a novel predictive model of high accuracy for the prognosis of IBC patients. Methods: Clinical information of 1,230 IBC patients from 2010 to 2020 was extracted from the Surveillance, Epidemiology and End Results (SEER) database. Cox analysis was applied to identify clinicopathological characteristics associated with the overall survival (OS) of IBC patients. Random survival forest (RSF) algorithm was adopted to construct an accurate prognostic prediction model for IBC patients. Kaplan–Meier analysis was performed for survival analyses. Results: Race, N stage, M stage, molecular subtype, history of chemotherapy and surgery, and response to neoadjuvant therapy were identified as independent predictive factors for the OS of IBC patients. The top five significant variables included surgery, response to neoadjuvant therapy, chemotherapy, breast cancer molecular subtypes, and M stage. The C-index of RSF model was 0.7704 and the area under curve (AUC) values for 1, 3, 5 years in training and validation datasets were 0.879–0.955, suggesting the excellent predictive performance of RSF model. IBC patients were divided into high-risk group and low-risk group according the risk score of RSF model, and the OS of patients in the low-risk group was significantly longer than those in the high-risk group. Conclusion: In this study, we constructed a prognosis prediction model for IBC patients through RSF algorithm, which may potentially serve as a useful tool during clinical decision-making.

Abstract Objective Early childhood caries has become a globally crucial oral health problem over the decades. Most studies have discussed the association between low birth weight and early childhood caries; however, studies focusing on high birth weight have been relatively limited. This study aimed to assess the impact of high birth weight on the incidence and severity of dental caries in 4–5-year-old children. Subjects and methods Study subjects included 491 children from a birth cohort study at 4–5 years of age. Data on dental caries, prenatal and perinatal factors, and socio-demographic determinants were recorded. Logistic regression models adjusted for potential confounders were performed to analyze the data. Two-sided P-value

Abstract Background Dental caries in young children is a difficult global oral health problem. In the last decade, China has put a great deal of effort into reducing the prevalence of dental caries. This study, which is part of the China Population Chronic Disease and Nutrition Surveillance 2021, aimed to investigate the prevalence of dental caries among children aged 5 in Shanghai, China, and its associated factors. Methods A total of 1281 children aged 5 years from 6 districts in Shanghai were selected by a stratified sampling method. The survey consisted of an oral health questionnaire and an oral health examination. The questionnaire included questions on oral health knowledge, attitudes, and behaviours. The oral health examination used WHO standards. After screening, the data were input and analysed. Chi-square tests and logistic regression analyses were used to study the relevant factors affecting dental caries. Results The prevalence of dental caries among 1281 children was 51.0%, the dmft index score was 2.46, the Significant Caries Index (SiC) score was 6.39, and the SiC10 score was 10.35. Dental caries experience was related to the frequency of sweet drink consumption, the age of starting tooth brushing, eating habits after brushing, whether the children had received an oral examination provided by the government (p 0.05). Logistic regression analysis showed that the region of residence, eating after brushing and the age of starting brushing were associated with dental caries. Conclusions Dental caries remained prevalent among 5-year-old children in Shanghai, China. Prevention strategies that target the associated factors including region of residence, eating after brushing, and the age of starting brushing should be considered.

Background: Using Mendelian randomization (MR) analysis, this study sought to determine the causal relationship between genetically predicted cheese intake, probiotics and breast cancer. Methods: A MR analysis including univariable and multivariable MR approaches using the public genome-wide association studies summary statistics was conducted to assess the causal effects. Results: Genetically predicted cheese intake per standard-deviation increase was associated with decreased risks of luminal A-like breast cancer (odds ratio [OR] = 0.80, 95 % confidence interval [CI]: 0.66–0.97, P = 0.03). No causal effect was detected between probiotics and breast cancer. Multivariable MR analysis showed that the causal effect between cheese intake and luminal A-like breast cancer might be driven by several major ingredients in cheese, including calcium, vitamin D and IGF-1 levels. Conclusions: Cheese intake is causally associated with luminal A-like breast cancer.

Abstract Examining patterns of genetic diversity are crucial for conservation planning on endangered species, while inferring the underlying process of recent anthropogenic habitat modifications in the context potential long‐term demographic changes remains challenging. The globally endangered scaly‐sided merganser (SSME), Mergus squamatus, is endemic to a narrow range in Northeast Asia, and its population has recently been contracted into two main breeding areas. Although low genetic diversity has been suggested in the Russian population, the genetic status and demographic history of these individuals have not been fully elucidated. We therefore examined the genetic diversity and structure of the breeding populations of the SSME and investigated the relative importance of historical and recent demographic changes to the present‐day pattern of genetic diversity. Using 10 nuclear microsatellite (SSR) markers and mitochondrial DNA (mtDNA) control region sequences, we found limited female‐inherited genetic diversity and a high level of nuclear genetic diversity. In addition, analysis of both markers consistently revealed significant but weak divergence between the breeding populations. Inconsistent demographic history parameters calculated from mtDNA and bottleneck analysis results based on SSR suggested a stable historical effective population size. By applying approximate Bayesian computation, it was estimated that populations started to genetically diverge from each other due to recent fragmentation events caused by anthropogenic effects rather than isolation during Last Glacial Maximum (LGM) and post‐LGM recolonization. These results suggest that limited historical population size and shallow evolutionary history may be potential factors contributing to the contemporary genetic diversity pattern of breeding SSME populations. Conservation efforts should focus on protecting the current breeding habitats from further destruction, with priority given to both the Russian and Chinese population, as well as restoring the connected suitable breeding grounds.

Abstract The high-resolution array is the basic structure of most kinds of microelectronics. Electrohydrodynamic jet (E-Jet) printing technology is widely applied in manufacturing array structures with high resolution, high material compatibility and multi-modal printing. It is still challenging to acquire high uniformity of printed array with micro-nanometer resolution, which greatly influences the performance and lifetime of the microelectronics. In this paper, to improve the uniformity of the printed array, the influence of each parameter on the uniformity of the E-jet printed dot array is studied on the cobuilt NEJ-E/P200 experimental platform, finding the applied voltage plays the most important role in maintaining the uniformity of the printed array. By appropriately adjusting the printing parameters, the dot arrays with different resolutions from 500 pixels per inch (PPI) to 17,000 PPI are successfully printed. For arrays below and over 10,000 PPI, the deviations of the uniformity are within 5% and 10% respectively. In this work, the dot array over 15,000 PPI is first implemented using E-jet printing. The conclusions acquired by experimental analysis of dot array printing process are of great importance in high resolution array printing as it provides practical guidance for parameters adjustment.

Abstract Background The large-scale application of pyrethroids and organophosphorus pesticides has great benefits for pest control. However, the increase of cancer incidence rate in recent years has also caused public concern about the health risks of pesticides. Hence, we utilized data from the National Health and Nutrition Examination Survey (NHANES) to assess the association and risk between pesticide exposure and several cancers, along with the comprehensive impact of oxidative stress. In this study, six cancers and six common pesticides were included to analyze their correlation and risk. And the levels of eight oxidative stress marks and two inflammatory markers were used for stratified analysis. Multiple logistic regression analysis was applied to estimate the odds ratio and 95% confidence intervals. Machine learning prediction models were established to evaluate the importance of different exposure factors. Results According to the data analyzed, each pesticide increased the risk of three to four out of six cancers on average. Iron, aspartate aminotransferase (AST), and gamma glutamyl transferase levels positively correlated with cancer risk in most cases of pesticide exposure. Except for demographic factors, factors such as AST, iron, and 3-phenoxybenzoic acid showed high contributions to the random forest model, which was consistent with our expectations. The receiver operating characteristic curve showed that the prediction model had sufficient accuracy (74.2%). Conclusion Our results indicated that specific pesticide exposure increased the risk of cancer, which may be mediated by various oxidative stress mechanisms. Additionally, some biochemical indicators have the potential to be screened for cancer prevention.

Abstract Introduction The rising prevalence of knee osteoarthritis is placing a considerable strain on the global healthcare system. To address this issue, telemedicine-supported multicomponent exercise therapy has emerged as a promising approach. This therapy combines exercise, patient education, and health coaching to empower knee osteoarthritis patients to manage their condition from the comfort of their homes. Nevertheless, there are some existing limitations in the current research on this approach, including challenges related to patient compliance and the absence of objective evaluation methods. Methods and analysis Patients diagnosed with knee osteoarthritis, who have not undergone knee surgery in the past year, will be recruited for a randomized controlled trial. The trial will include an intervention group and a control group. The intervention group will receive an mHealth app-based multicomponent exercise therapy, consisting of exercise therapy, patient education, and health coaching. Meanwhile, the control group will receive usual care, involving drug therapy and patient education. The primary outcome of the trial will be the measurement of pain intensity, assessed using a visual analog scale at baseline and at 4, 8, and 12 weeks of the post-intervention. To analyze the data, a two-factor, four-level repeated measures ANOVA will be used if the assumptions of homogeneity of variance and sphericity are met. If not, a mixed effects model will be employed. Discussion The aim of the study is to evaluate the effectiveness of multicomponent exercise therapy aimed at enhancing pain self-management for knee osteoarthritis patients in the comfort of their own homes. The intervention incorporate wearable devices equipped with advanced deep learning systems to monitor patients' adherence to the prescribed at-home exercise regimen, as well as to track changes in outcomes before and after the exercise sessions. The findings from this trial have the potential to enhance both the accessibility and quality of care provided to knee osteoarthritis patients, offering valuable insights for future improvements in their treatment and management. Trial registration Chinese Clinical Trials Registry, ChiCTR2300073688. Registered on 19 July 2023, https://www.chictr.org.cn/bin/project/edit?pid=199707 . World Health Organization International Clinical Trials Registry Platform, https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300073688 .

Summary: Background: Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown. Methods: In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline. Findings: One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH. Interpretation: Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants. Funding: This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, under Award No. U19AI145825. N.D. is a clinical researcher and A.M. is Research Director at the Fonds de la Recherche Scientifique (F.R.S.-FNRS), Belgium. M.E.A. was partially supported by NIH NIAID 1U19AI14825. This article is published with the support of the Fondation Universitaire of Belgium.

ABSTRACTResearch has indicated that intratumor microbiomes affect the occurrence, progression, and therapeutic response in many cancer types by influencing the immune system. We aim to evaluate the characteristics of immune-related intratumor microbiomes (IRIMs) in breast cancer (BC) and search for potential prognosis prediction factors and treatment targets. The clinical information, microbiome data, transcriptomics data of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) patients were obtained from Kraken-TCGA-Raw-Data and TCGA portal. The core tumor-infiltrating immune cell was identified using univariate Cox regression analysis. Based on consensus clustering analysis, BC patients were categorized into two immune subtypes, referred to as immune-enriched and immune-deficient subtypes. The immune-enriched subtype, characterized by higher levels of immune infiltration of CD8+ T and macrophage M1 cells, demonstrated a more favorable prognosis. Furthermore, significant differences in alpha-diversity and beta-diversity were observed between the two immune subtypes, and the least discriminant analysis effect size method identified 33 types of IRIMs. An intratumor microbiome-based prognostic signature consisting of four prognostic IRIMs (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania) was constructed using the Cox proportional-hazard model, and it had great prognostic value. The prognostic IRIMs were correlated with immune gene expression and the sensitivity of chemotherapy drugs, specifically tamoxifen and docetaxel. In conclusion, our research has successfully identified two distinct immune subtypes in BC, which exhibit contrasting prognoses and possess unique epigenetic and intratumor microbiomes. The critical IRIMs were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in BC. Consequently, this study has identified potential IRIMs as biomarkers, providing a novel therapeutic approach for treating BC.IMPORTANCERecent research has substantiated the presence of the intratumor microbiome in tumor immune microenvironment, which could influence tumor occurrence and progression, as well as provide new opportunities for cancer diagnosis and treatment. This study identified the critical immune-related intratumor microbiome (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania), which were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in breast cancer and might be the novel target to regulate immunotherapy in BC.

Abstract This study used the Baidu Index to analyze searches using discriminatory language toward the source of the outbreak during the initial stages of the COVID-19 pandemic. The study found a strong correlation between official intervention and a reduction in searches using discriminatory language. Following the official naming of the virus bt the government, the general public understood that searches using discriminatory language should be avoided, and search behavior dramatically changed. Meanwhile, this study also found that official intervention also overcame the effects of local socioeconomic factors. Regions with higher levels of socioeconomic development and higher population density had a stronger discriminatory language in internet searches, while the opposite was the case for regions with lower CPI and unemployment rates. However, after the official intervention, these factors no longer had a significant effect. It is recommended that officials worldwide provide early official media guidance during infectious disease outbreaks to reduce the use of discriminatory language and ensure the delivery of transparent and effective information to the public.

Abstract Background Several observational studies have explored the associations between Sjögren’s syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers. Methods We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P

Abstract Background The main purpose of the study was to investigate the prevalence and related risk factors of malocclusion in permanent dentition among adolescents in Shanghai, and provide basic data for government’s preventive strategies and intervention plans. Methods 1799 adolescents aged 11–15 years old from 18 middle schools in 6 districts of Shanghai were recruited to investigate oral health status and related risk factors using cluster random sampling method in 2021. Malocclusion and caries were examined by on-site inspection. The investigation criteria referred to Bjoerk and the recommendation of the WHO. The malocclusion inspection items included molars relationship, canine relationship, overbite, overjet, midline displacement, anterior crossbite, posterior crossbite, scissors bite, crowding and spacing. The subjects were asked to fill in a questionnaire including parents’ education level, oral health behaviors and dietary habits. The chi-square test and logistic regression analysis were used to analyze the relationship between malocclusion and risk factors. Results 1799 adolescents were included in the study and the prevalence of malocclusion in adolescents in Shanghai was 83.5%, and the proportion of molar relationship class I, class II, and class III was 48.9%, 14.7%, and 19.0%, respectively. The most common occlusal characteristic of malocclusion was anterior crowding, followed by midline irregularities and deep overbite, with prevalence rates of 44.8%, 39.0% and 38.6%, respectively. The prevalence rate of adolescents with caries was 34.3%. Those who had dental caries and preferred soft food were more likely to have abnormal occlusal characteristics (p

Tumor recurrence and tissue regeneration are two major challenges in the postoperative treatment of cancer. Current research hotspots are focusing on developing novel scaffold materials that can simultaneously suppress tumor recurrence and promote tissue repair. Here, we propose a microfluidic 3D-printed methacrylate fish gelatin (F-GelMA@BBR) scaffold loaded with berberine (BBR) for the postoperative treatment of gastric cancer. The F-GelMA@BBR scaffold displayed a significant killing effect on gastric cancer MKN-45 cells in vitro and demonstrated excellent anti-recurrence efficiency in gastric cancer postoperative models. In vitro experiments have shown that F-GelMA@BBR exhibits significant cytotoxicity on gastric cancer cells while maintaining the cell viability of normal cells. The results of in vivo experiments show that F-GelMA@BBR can significantly suppress the tumor volume to 49.7 % of the control group. In addition, the scaffold has an ordered porous structure and good biocompatibility, which could support the attachment and proliferation of normal cells to promote tissue repair at the tumor resection site. These features indicated that such scaffold material is a promising candidate for postoperative tumor treatment in the practical application.

Abstract Background Breast cancer brain metastases (BCBM) are the most fatal, with limited survival in all breast cancer distant metastases. These patients are deemed to be incurable. Thus, survival time is their foremost concern. However, there is a lack of accurate prediction models in the clinic. What’s more, primary surgery for BCBM patients is still controversial. Methods The data used for analysis in this study was obtained from the SEER database (2010–2019). We made a COX regression analysis to identify prognostic factors of BCBM patients. Through cross-validation, we constructed XGBoost models to predict survival in patients with BCBM. Meanwhile, a BCBM cohort from our hospital was used to validate our models. We also investigated the prognosis of patients treated with surgery or not, using propensity score matching and K–M survival analysis. Our results were further validated by subgroup COX analysis in patients with different molecular subtypes. Results The XGBoost models we created had high precision and correctness, and they were the most accurate models to predict the survival of BCBM patients (6-month AUC = 0.824, 1-year AUC = 0.813, 2-year AUC = 0.800 and 3-year survival AUC = 0.803). Moreover, the models still exhibited good performance in an externally independent dataset (6-month: AUC = 0.820; 1-year: AUC = 0.732; 2-year: AUC = 0.795; 3-year: AUC = 0.936). Then we used Shiny-Web tool to make our models be easily used from website. Interestingly, we found that the BCBM patients with an annual income of over USD$70,000 had better BCSS (HR = 0.523, 95%CI 0.273–0.999, P

Abstract 3D morphable models (3DMMs) are generative models for face shape and appearance. Recent works impose face recognition constraints on 3DMM shape parameters so that the face shapes of the same person remain consistent. However, the shape parameters of traditional 3DMMs satisfy the multivariate Gaussian distribution. In contrast, the identity embeddings meet the hypersphere distribution, and this conflict makes it challenging for face reconstruction models to preserve the faithfulness and the shape consistency simultaneously. In other words, recognition loss and reconstruction loss can not decrease jointly due to their conflict distribution. To address this issue, we propose the Sphere Face Model (SFM), a novel 3DMM for monocular face reconstruction, preserving both shape fidelity and identity consistency. The core of our SFM is the basis matrix which can be used to reconstruct 3D face shapes, and the basic matrix is learned by adopting a two-stage training approach where 3D and 2D training data are used in the first and second stages, respectively. We design a novel loss to resolve the distribution mismatch, enforcing that the shape parameters have the hyperspherical distribution. Our model accepts 2D and 3D data for constructing the sphere face models. Extensive experiments show that SFM has high representation ability and clustering performance in its shape parameter space. Moreover, it produces high-fidelity face shapes consistently in challenging conditions in monocular face reconstruction. The code will be released at https://github.com/a686432/SIR

ABSTRACTThe association between the oral microbiome and mild cognitive impairment (MCI) remains unclear. This study aimed to investigate such an association among Chinese older adults. Participants without dementia were recruited from the community. A battery of neuropsychological tests was administered to evaluate the cognitive function. The diagnosis of MCI was based on Peterson’s criteria. The non-stimulated saliva was collected to extract sequences of the oral microbiome. Forty-seven MCI and 47 cognitively normal participants were included. There was significant difference in alpha diversity and insignificant difference in beta diversity between the two groups of participants. Compared with the cognitively normal group, Gemella haemolysans and Streptococcus gordonii were two significantly decreased species while Veillonella unclassified_Veillonella and Fusobacterium sp._HMT_203 were two significantly increased species in the MCI group. The richness of Gemella haemolysans presented the best discriminate value for MCI with the AUC (Area Under Curve) of 0.707, a cut-off value of 0.008 for relative abundance, the sensitivity of 63.8% and specificity of 70.2%. The dysbiosis of oral microbiome and relative abundance of Gemella haemolysans was significantly associated with MCI. Further studies were needed to develop new treatment strategies targeting the oral microbiome for cognitive impairment.

Abstract Kentucky bluegrass (Poa pratensis L.) cultivars are diverse in their phenotype with a common classification system used to describe their growth habit but it is unclear why their growth differs. Growth analysis measurements have been used to explain growth rate differences among grass species and cultivars. The objective of this experiment was to study the growth of six commercially available Kentucky bluegrass cultivars from different growth habit classifications using classical growth analysis. Kentucky bluegrass seed was germinated and transplanted into cone‐tainers and transferred to a growth chamber maintained at 25/15°C (day/night) and a 12‐h photoperiod. Thirty plants per cultivar were used with six whole plants of each cultivar harvested 8 weeks after transplanting and once per week for the next 4 weeks for a total of five harvests. Barvette HGT produced the largest plants, and Moonlight SLT produced the smallest plants by the end of the experiment, although the relative growth rate and absolute growth rate did not vary between the cultivars. Results from the growth analysis revealed that Moonlight SLT had the highest leaf area ratio (89.4 cm2 g−1), specific leaf area (200.1 cm2 g−1), and rhizome weight ratio (0.101 g g−1), but the lowest stem weight ratio (0.120 g g−1) and root weight ratio (0.338 g g−1). Final plant weights and leaf area measurements were closely aligned with Kentucky bluegrass classification information. Unfortunately, classical growth analysis provided little insight into why some cultivars possess more aggressive growth characteristics or compact growth habits.

In this paper, a novel boundary layer enhancement structure as well as various bluff body arrangement strategies were proposed to optimize the voltage output performance of a piezoelectric vibration-based energy harvest equipment. A systematic investigation in both numerical and experimental approaches revealed that an inversed 6-cylinder bluff body arrangement yielded significantly better voltage output performance than the previously reported dual-cylinder arrangement. A positive correlation can be observed between both flow velocity and the voltage output, and the cantilever beam tends to oscillate at a slightly higher frequency under a higher inflow velocity. A very noticeable improvement was observed when the proposed wall structure was applied, and our numerical study revealed that the wall structure induced a relatively stable layer of fluid near the wall and led to a much more chaotic wake of the bluff bodies which may account for the performance improvement of the system.

Kentucky bluegrass (Poa pratensis L.) is an eminent turfgrass species with a complex genome, but it is sensitive to rust (Puccinia striiformis). The molecular mechanisms of Kentucky bluegrass in response to rust still remain unclear. This study aimed to elucidate differentially expressed lncRNAs (DELs) and genes (DEGs) for rust resistance based on the full-length transcriptome. First, we used single-molecule real-time sequencing technology to generate the full-length transcriptome of Kentucky bluegrass. A total of 33,541 unigenes with an average read length of 2,233 bp were obtained, which contained 220 lncRNAs and 1,604 transcription factors. Then, the comparative transcriptome between the mock-inoculated leaves and rust-infected leaves was analyzed using the full-length transcriptome as a reference genome. A total of 105 DELs were identified in response to rust infection. A total of 15,711 DEGs were detected (8,278 upregulated genes, 7,433 downregulated genes) and were enriched in plant hormone signal transduction and plant–pathogen interaction pathways. Additionally, through co-location and expression analysis, it was found that lncRNA56517, lncRNA53468, and lncRNA40596 were highly expressed in infected plants and upregulated the expression of target genes AUX/IAA, RPM1, and RPS2, respectively; meanwhile, lncRNA25980 decreased the expression level of target gene EIN3 after infection. The results suggest that these DEGs and DELs are important candidates for potentially breeding the rust-resistant Kentucky bluegrass.

IntroductionThe loss of occlusal support due to tooth loss is associated with systemic diseases. However, there was little about the association between occlusal support and cognitive impairment. The cross-sectional study aimed to investigate their association.MethodsCognitive function was assessed and diagnosed in 1,225 community-dwelling adults aged 60 years or older in Jing’an District, Shanghai. Participants were diagnosed with mild cognitive impairment (MCI) by Peterson’s criteria, or dementia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We determined the number of functional occlusal supporting areas according to Eichner classifications. We used multivariate logistic regression models to analyze the relationship between occlusal support and cognitive impairment and mediation effect models to analyze the mediation effect of age.ResultsSix hundred sixty participants were diagnosed with cognitive impairment, averaging 79.92 years old. After adjusting age, sex, education level, cigarette smoking, alcohol drinking, cardiovascular disease, and diabetes, individuals with poor occlusal support had an OR of 3.674 (95%CI 1.141–11.829) for cognitive impairment compared to those with good occlusal support. Age mediated 66.53% of the association between the number of functional occlusal supporting areas and cognitive impairment.DiscussionIn this study, cognitive impairment was significantly associated with the number of missing teeth, functional occlusal areas, and Eichner classifications with older community residents. Occlusal support should be a significant concern for people with cognitive impairment.

Abstract Methyl jasmonate (MeJA) plays a role in improving plant stress tolerance. The molecular mechanisms associated with heat tolerance mediated by MeJA are not fully understood in perennial grass species. The study was designed to explore transcriptomic mechanisms underlying heat tolerance by exogenous MeJA in perennial ryegrass (Lolium perenne L.) using RNA-seq. Transcriptomic profiling was performed on plants under normal temperature (CK), high temperature for 12 h (H), MeJA pretreatment (T), MeJA pretreatment + H (T-H), respectively. The analysis of differentially expressed genes (DEGs) showed that H resulted in the most DEGs and T had the least, compared with CK. Among them, the DEGs related to the response to oxygen-containing compound was higher in CKvsH, while many genes related to photosynthetic system were down-regulated. The DEGs related to plastid components was higher in CKvsT. GO and KEGG analysis showed that exogenous application of MeJA enriched photosynthesis related pathways under heat stress. Exogenous MeJA significantly increased the expression of genes involved in chlorophyll (Chl) biosynthesis and antioxidant metabolism, and decreased the expression of Chl degradation genes, as well as the expression of heat shock transcription factor - heat shock protein (HSF-HSP) network under heat stress. The results indicated that exogenous application of MeJA improved the heat tolerance of perennial ryegrass by mediating expression of genes in different pathways, such as Chl biosynthesis and degradation, antioxidant enzyme system, HSF-HSP network and JAs biosynthesis.

Breast cancer (BC) has the highest incidence rate of all cancers globally, with high heterogeneity. Increasing evidence shows that lactate and long non-coding RNA (lncRNA) play a critical role in tumor occurrence, maintenance, therapeutic response, and immune microenvironment. We aimed to construct a lactate-related lncRNAs prognostic signature (LRLPS) for BC patients to predict prognosis, tumor microenvironment, and treatment responses. The BC data download from the Cancer Genome Atlas (TCGA) database was the entire cohort, and it was randomly assigned to the training and test cohorts at a 1:1 ratio. Difference analysis and Pearson correlation analysis identified 196 differentially expressed lactate-related lncRNAs (LRLs). The univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to construct the LRLPS, which consisted of 7 LRLs. Patients could be assigned into high-risk and low-risk groups based on the medium-risk sore in the training cohort. Then, we performed the Kaplan–Meier survival analysis, time-dependent receiver operating characteristic (ROC) curves, and univariate and multivariate analyses. The results indicated that the prognosis prediction ability of the LRLPS was excellent, robust, and independent. Furthermore, a nomogram was constructed based on the LRLPS risk score and clinical factors to predict the 3-, 5-, and 10-year survival probability. The GO/KEGG and GSEA indicated that immune-related pathways differed between the two-risk group. CIBERSORT, ESTIMATE, Tumor Immune Dysfunction and Exclusion (TIDE), and Immunophenoscore (IPS) showed that low-risk patients had higher levels of immune infiltration and better immunotherapeutic response. The pRRophetic and CellMiner databases indicated that many common chemotherapeutic drugs were more effective for low-risk patients. In conclusion, we developed a novel LRLPS for BC that could predict the prognosis, immune landscape, and treatment response.

The construction of defects in semiconductor photocatalysts, as a kind of modification methods, plays an indispensable role in the enhancement of the photocatalytic performance. Herein, nitrogen defects were successfully introduced into the framework of graphite carbon nitride (CN-Tx) through thermal polymerization with melamine and 1,2,4-triazole as precursors. The existence of nitrogen defects in CN-Tx were confirmed to be located at the two-coordinated (N2c) CN–C lattice sites, which resulted in the destruction of its planar structure and the initiation of n-π∗ electron transition that greatly expanded the response range to visible light and improved the separation efficiency of photogenerated charge carrier. More significantly, CN-Tx could enhance photocatalytic water purification activity towards different kinds of pollutants. The photocatalytic rates of CN-T3 were estimated to be 2.54 (tetracycline) and 2.31 (2-hydroxynaphthalene) times higher than those of pristine g-C3N4. Furthermore, the possible photocatalytic degradation mechanism over CN-Tx photocatalyst was proposed by free radical trapping experiments combined with ERS characterization. This work provides an in-depth understanding of the important role of nitrogen defects in the electronic structure and chemical properties of g-C3N4 and its photocatalytic water purification performance.

Breast cancer (BC) is the most diagnosed cancer in women. Cuproptosis is new regulated cell death, distinct from known death mechanisms and dependent on copper and mitochondrial respiration. However, the comprehensive relationship between cuproptosis and BC is still blank until now. In the present study, we acquired 13 cuproptosis-related regulators (CRRs) from the previous research and downloaded the RNA sequencing data of TCGA-BRCA from the UCSC XENA database. The 13 CRRs were all differently expressed between BC and normal samples. Using consensus clustering based on the five prognostic CRRs, BC patients were classified into two cuproptosis-clusters (C1 and C2). C2 had a significant survival advantage and higher immune infiltration levels than C1. According to the Cox and LASSO regression analyses, a novel cuproptosis-related prognostic signature was developed to predict the prognosis of BC effectively. The high- and low-risk groups were divided based on the risk scores. Kaplan-Meier survival analysis indicated that the high-risk group had shorter overall survival (OS) than the low-risk group in the training, test and entire cohorts. GSEA indicated that the immune-related pathways were significantly enriched in the low-risk group. According to the CIBERSORT and ESTIMATE analyses, patients in the high-risk group had higher infiltrating levels of antitumor lymphocyte cell subpopulations and higher immune score than the low-risk group. The typical immune checkpoints were all elevated in the high-risk group. Furthermore, the high-risk group showed a better immunotherapy response than the low-risk group based on the Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenoscore (IPS). In conclusion, we identified two cuproptosis-clusters with different prognoses using consensus clustering in BC. We also developed a cuproptosis-related prognostic signature and nomogram, which could indicate the outcome, the tumor immune microenvironment, as well as the response to immunotherapy.

Occlusal support was proved to be associated with type 2 diabetes. Our aim was to investigate the association between the Eichner index and the prevalence of type 2 diabetes. We included 715 participants with oral health examinations in the Shanghai Aging Study. The occlusal support status was determined by the number of functional occlusal support areas and Eichner index classifications. Those with fasting plasma glucose ≥126 mg/dL and/or hemoglobin A1c ≥6.5% and/or current medications for type 2 diabetes with relevant medical history were diagnosed with type 2 diabetes. Multiple logistic regression models were used to analyze the relationship between occlusal support status and type 2 diabetes. The average age of 715 participants was 73.74 ± 6.49 years old. There were 84 diabetics with 1.71 occlusal supporting areas on average. Seven hundred and fifteen participants were divided into 3 groups according to Eichner classifications: Eichner group A with 4 occlusal functional areas, Eichner group B with 1-3 occlusal functional areas or 0 area with anterior occlusal contact, and Eichner group C with no functional occlusal contact. Blood glucose level was significantly lower in participants of Eichner group A compared to those in group B or C. The ordinal logistic regression showed more occlusal supporting areas were significantly associated with less type 2 diabetes cases with an Odds Ratio(OR) of 0.253(95%CI 0.108-0.594) after adjusting covariates. Participants in Eichner group A had a significantly much lower OR of 0.078 for type 2 diabetes (95%CI 0.009-0.694) compared to those in Eichner group C after adjustment. The number of functional occlusal support areas might be inversely related to the blood glucose level and the prevalence of type 2 diabetes.

Abstract Background Identification of genetic diversity in heat tolerance and associated traits is of great importance for improving heat tolerance in cool-season grass species. The objectives of this study were to determine genetic variations in heat tolerance associated with phenotypic and physiological traits and to identify molecular markers associated with heat tolerance in a diverse collection of perennial ryegrass (Lolium perenne L.). Results Plants of 98 accessions were subjected to heat stress (35/30 °C, day/night) or optimal growth temperature (25/20 °C) for 24 d in growth chambers. Overall heat tolerance of those accessions was ranked by principal component analysis (PCA) based on eight phenotypic and physiological traits. Among these traits, electrolyte leakage (EL), chlorophyll content (Chl), relative water content (RWC) had high correlation coefficients (− 0.858, 0.769, and 0.764, respectively) with the PCA ranking of heat tolerance. We also found expression levels of four Chl catabolic genes (CCGs), including LpNYC1, LpNOL, LpSGR, and LpPPH, were significant higher in heat sensitive ryegrass accessions then heat tolerant ones under heat stress. Furthermore, 66 pairs of simple sequence repeat (SSR) markers were used to perform association analysis based on the PCA result. The population structure of ryegrass can be grouped into three clusters, and accessions in cluster C were relatively more heat tolerant than those in cluster A and B. SSR markers significantly associated with above-mentioned traits were identified (R 2 > 0.05, p

Abstract Background The signal peptides (SPs) of secretory proteins are frequently used or modified to guide recombinant proteins outside the cytoplasm of prokaryotic cells. In the periplasmic space and extracellular environment, recombinant proteins are kept away from the intracellular proteases and often they can fold correctly and efficiently. Consequently, expression levels of the recombinant protein can be enhanced by the presence of a SP. However, little attention has been paid to the use of SPs with low translocation efficiency for recombinant protein production. In this paper, the function of the signal peptide of Bacillus thuringiensis (Bt) Cry1Ia toxin (Iasp), which is speculated to be a weak translocation signal, on regulation of protein expression was investigated using fluorescent proteins as reporters. Results When fused to the N-terminal of eGFP or mCherry, the Iasp can improve the expression of the fluorescent proteins and as a consequence enhance the fluorescent intensity of both Escherichia coli and Bt host cells. Real-time quantitative PCR analysis revealed the higher transcript levels of Iegfp over those of egfp gene in E. coli TG1 cells. By immunoblot analysis and confocal microscope observation, lower translocation efficiency of IeGFP was demonstrated. The novel fluorescent fusion protein IeGFP was then used to compare the relative strengths of cry1Ia (P i ) and cry1Ac (P ac ) gene promoters in Bt strain, the latter promoter proving the stronger. The eGFP reporter, by contrast, cannot indicate unambiguously the regulation pattern of P i at the same level of sensitivity. The fluorescent signals of E. coli and Bt cells expressing the Iasp fused mCherry (ImCherry) were also enhanced. Importantly, the Iasp can also enhanced the expression of two difficult-to-express proteins, matrix metalloprotease-13 (MMP13) and myostatin (growth differentiating factor-8, GDF8) in E. coli BL21-star (DE3) strain. Conclusions We identified the positive effects of a weak signal peptide, Iasp, on the expression of fluorescent proteins and other recombinant proteins in bacteria. The produced IeGFP and ImCherry can be used as novel fluorescent protein variants in prokaryotic cells. The results suggested the potential application of Iasp as a novel fusion tag for improving the recombinant protein expression.

The global phenomenon of coral bleaching under thermal stress has been recognized as the primary driver underlying coral reef degradation. The coral bacterial community plays an important role in the stability of coral reef ecosystem. Dimethylsulfoniopropionate (DMSP) and its associated metabolites are essential for the establishment of coral bacterial communities and provide key benefits for overall coral health and bleaching recovery. Substantial research to date has focused on the bacterial community composition, metabolism and functional properties within the coral holobiont, but less attention has been paid to the role of bacteria in seawater surrounding corals under thermal stress. Here, we investigated bacterial community composition, biological functions and DMSP metabolism changes of the seawater surrounding corals under thermal stress. We found that microbial community in seawater surrounding corals changed under thermal stress, and corals bleached eventually. The abundance of Rhodobacterales, Flavobacteriales and Rhizobiales increased while Chitinophagales and SAR11 decreased as temperature elevated. Correspondingly, stress tolerant, biofilm forming and mobile elements increased, resulting in large part from changes in Rhodobacterales and Phaeodactylibacter abundance. DMSP producing and catabolic levels in seawater surrounding corals were enhanced under thermal stress with higher dsyB (1.46-fold), dddP (2.43-fold) and dmdA (1.47-fold) detected. This study reveals the biological functions and metabolisms of bacteria in the water surrounding corals, providing valuable insight on how these communities and functions change in coral reef ecosystem under thermal stress.

Alfalfa (Medicago sativa L.) is a perennial forage crop known as the “Queen of Forages.” To dissect the genetic mechanism of flowering time (FT) in alfalfa, high−density linkage maps were constructed for both parents of an F1 mapping population derived from a cross between Cangzhou (P1) and ZhongmuNO.1 (P2), consisting of 150 progenies. The FT showed a transgressive segregation pattern in the mapping population. A total of 13,773 single-nucleotide polymorphism markers was obtained by using restriction-site associated DNA sequencing and distributed on 64 linkage groups, with a total length of 3,780.49 and 4,113.45 cM and an average marker interval of 0.58 and 0.59 cM for P1 and P2 parent, respectively. Quantitative trait loci (QTL) analyses were performed using the least square means of each year as well as the best linear unbiased prediction values across 4 years. Sixteen QTLs for FT were detected for P1 and 22 QTLs for P2, accounting for 1.40–16.04% of FT variation. RNA-Seq analysis at three flowering stages identified 5,039, 7,058, and 7,996 genes that were differentially expressed between two parents, respectively. Based on QTL mapping, DEGs analysis, and functional annotation, seven candidate genes associated with flowering time were finally detected. This study discovered QTLs and candidate genes for alfalfa FT, making it a useful resource for breeding studies on this essential crop.

Kentucky bluegrass (Poa pratensis L.) is a cool-season turfgrass species that responds strongly to nitrogen (N), but the metabolomic responses of this grass species to N supply is unknown. The N-tolerant cultivar Bluemoon and N-sensitive cultivar Balin were exposed to normal N (15 mM) and low N (0.5 mM) for 21 days for identification of differentially expressed metabolites (DEMs) between normal N and low N treatments. Balin had more reductions of chlorophyll and total soluble protein concentrations and a higher accumulation of superoxide radicals under low N stress. A total of 99 known DEMs were identified in either cultivar or both including 22 amino acids and derivatives, 16 carbohydrates, 29 organic acids, and 32 other metabolites. In Bluemoon, β-alanine metabolism was most enriched, followed by alanine, aspartate, and glutamate metabolism, biosynthesis of valine, leucine, and isoleucine biosynthesis, and glycine, serine, and threonine metabolism. In Balin, alanine, aspartate, and glutamate metabolism were most enriched, followed by the tricarboxylic acid (TCA), glyoxylate and decarbohydrate metabolism, and carbon fixation. Bluemoon generally maintained higher TCA cycle capacity and had more downregulated amino acids, while changes in more organic acids occurred in Balin under low N stress. Some metabolite changes by low-N stress were cultivar-specific. The results suggested that regulation of metabolites related to energy production or energy saving could contribute to low N tolerance in Kentucky bluegrass.

The shipping industry has accelerated the transformation of its carbon emission reduction and decarbonization, and relevant patents are rapidly increasing, but the industry still lacks consensus on the low-carbon development route of ship propulsion technology. We used the Derwent Innovation Index to collect the global patent information on ship power systems between 1965 and 2022 and proposed a new patent information mining framework. It is used for the dynamic tracking and analysis of global technology correlation characteristics, hot technology topics, and competitive situations. The findings indicate that: (1) the innovation of ship power systems is more radical and concentrated in the fuel field represented by LNG technology, whereas technical innovation in the field of pure electric propulsion is more scattered. Small tonnage ships, underwater operations, and recreation technology are among its innovation hotspots. (2) Pure electric propulsion technology is dominated by combined innovation with other propulsion methods (hybrid propulsion technology) and Chinese universities have recently begun to lead this technology. (3) Fuel cells and remote control have become innovation hotspots. Fuel cell technology, which combines electric, fuel, and hybrid power technology, is now on the cutting edge of innovation and has the potential for disruptive innovation.

Abstract Background The purpose of the study is to examine the association between tooth loss and hypertension among older community residents in urban China. Methods This study included 3677 participants aged ≥50 years from the Shanghai Aging Study. We determined the number of teeth missing from questionnaires. Hypertension was defined as the mean of two measurements of systolic blood pressure (SBP) (140 mmHg or higher), diastolic blood pressure (DBP) (90 mmHg or higher) or physician-diagnosed hypertension confirmed from medical records. A multivariable logistic regression model was used to investigate the association between tooth loss and hypertension. Results The average number of missing teeth among study participants was 9.67. Among them, participants with hypertension had lost an average of 10.88 teeth, significantly higher than those without hypertension (8.95) (p

During the development and construction of the Puguang Gas Field, Sichuan Basin, an advanced automatic control system and a fully covered industrial Internet of Things were built. In order to further increase its development benefit, the Puguang Gas Field started the construction of an intelligent gas-field project in 2013. However, there are not mature models and construction standards of intelligent oil and gas fields at home and abroad for reference. In this paper, an overall architecture design of intelligent gas field and its technical and business architecture design were demonstrated according to the principle of “overall planning, step-by-step implementation, response in each step and stressing the main points”, and based on the mainstream design concept and practical experience of intelligentization. Then, combined with the key business target and implementation principle of the gas field, it was conducted and applied. And the following research results were obtained. First, the overall architecture of the intelligent gas field project includes a platform, two centers and two systems, i.e., integrated coordinated application platform, resource sharing center, intelligently assistant decision-making direction center, standard specification system and information safety system. Second, the technical architecture consists of four layers, i.e., industrial Internet of Things + equipment perception introducing layer, infrastructure cloud service layer, platform cloud service layer and software cloud service layer. Third, the business architecture is designed focusing on four support units, including exploration and development management of the gas field, production and emergency direction management of gas field, QHSE management of gas field and business management of the gas field. Fourth, the construction of the intelligent gas field project creates four abilities, i.e., assistant exploration and development decision-marking ability, production optimization and coordination ability, safety control and treatment ability and refined business management ability, to support the smooth operation, efficient management and safe production of the Puguang Gas Field. In conclusion, the intelligent management and decision-making system with the resource sharing center as the base, the integrated platform as the core and two systems as the guarantee has been preliminarily built in the Puguang Gas Field. Keywords: Intelligent gas field, Puguang gas field, Architecture design, Internet of things, Big data, Cloud technology, Assistant decision-making

During the initial construction of the Puguang Gas Field, information infrastructure was built. Due to the absence of unified planning and deployment, however, many “isolated information islands” were formed in data systems, and the data resources cannot meet the construction requirements of intelligent gas field. In this paper, the status quo and problems of data resources in the Puguang Gas Field were analyzed, and a data resource sharing center was constructed according to the overall architecture design of the Puguang Intelligent Gas Field. Based on the architecture design of data resource sharing center, the overall construction conception of data resource sharing center was put forward and the business data model was designed. Finally, the integrated data collection, storage, calculation and utilization was realized by establishing data standard, combing data sources and designing data services, and then it was applied on site. The following research results were obtained. First, the data resource sharing center is an important foundation for the construction of this project, and its overall architecture is divided into three layers from bottom to top, i.e., data specification and standard, data collection, storage, calculation and utilization, and data control. Second, the data resource sharing center achieves the one-time collection, centralized storage, shared use and unified management of exploration & development, gathering & purification, production & operation and safety & environmental protection data, and provides an important data base for the construction of business system of the intelligent gas field and a comprehensive, reliable and effective data support for the intelligent and mobile application in the Puguang Gas Field. Keywords: Intelligent gas field, Puguang gas field, Standard and specification, Post data, Real time data, Video data, Distributed storage, Data sharing service

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) levels by facilitating the degradation of the LDL receptor (LDLR) and is an attractive therapeutic target for hypercholesterolemia intervention. Herein, we generated a novel fully human antibody with favourable druggability by utilizing phage display-based strategy. Methods: A potent single-chain variable fragment (scFv) named AP2M21 was obtained by screening a fully human scFv phage display library with hPCSK9, and performing two in vitro affinity maturation processes including CDR-targeted tailored mutagenesis and cross-cloning. Thereafter, it was transformed to a full-length Fc-silenced anti-PCSK9 antibody FAP2M21 by fusing to a modified human IgG1 Fc fragment with L234A/L235A/N297G mutations and C-terminal lysine deletion, thus eliminating its immune effector functions and mitigating mAb heterogeneity. Findings: Our data showed that the generated full-length anti-PCSK9 antibody FAP2M21 binds to hPCSK9 with a KD as low as 1.42 nM, and a dramatically slow dissociation rate (koff, 4.68 × 10−6 s−1), which could be attributed to its lower binding energy (-47.51 kcal/mol) than its parent counterpart FAP2 (-30.39 kcal/mol). We verified that FAP2M21 potently inhibited PCSK9-induced reduction of LDL-C uptake in HepG2 cells, with an EC50 of 43.56 nM. Further, in hPCSK9 overexpressed C57BL/6 mice, a single tail i.v. injection of FAP2M21 at 1, 3 and 10 mg/kg, dose-dependently up-regulated hepatic LDLR levels, and concomitantly reduced serum LDL-C by 3.3% (P = 0.658, unpaired Student's t-test), 30.2% (P = 0.002, Mann-Whitney U-test) and 37.2% (P = 0.002, Mann-Whitney U-test), respectively. Interpretation: FAP2M21 with potent inhibitory effect on PCSK9 may serve as a promising therapeutic agent for treating hypercholesterolemia and associated cardiovascular diseases.

Background: Triple negative breast cancer (TNBC), a fatal malignant tumor, is characterized by a lack of estrogen and progesterone hormone receptors and overexpression of HER2. Due to its characteristics, there are no effective targeted therapies for TNBC. Therefore, it is critical to identify the crucial factors that participate in modulating TNBC progression and explore the underlying molecular mechanism.Methods: CCK-8, bromodeoxyuridine incorporation, western blotting, qPCR, and transwell assays were utilized to evaluate breast cancer cell proliferation, migration, and invasion.Results: Activation of platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR) promoted the proliferation and metastatic phenotype of TNBC cells; however, these effects were attenuated by SHP-2 knockdown. Moreover, PDGF-B promoted the expression of zinc finger E-box binding homeobox 1 (ZEB1) by downregulating the expression of miR-200. Furthermore, knockdown of ZEB1 mitigated the promoting effects of PDGF-B on cell proliferation and migration. In addition, the regulatory effects of PDGF-B on miR-200 and ZEB1 were mediated through the SHP-2/Akt pathway.Conclusion: Our findings highlight the important roles of PDGF-B/PDGFR and their downstream signaling pathways in regulating cell proliferation and metastatic phenotype in TNBC. Hence, these molecules may serve as novel therapeutic targets for TNBC in the future.

Abstract Background Accumulation of cadmium (Cd) in maize (Zea mays L.) poses a significant risk to human health as it is ingested via the food chain. A genome-wide association study (GWAS) was conducted in a population of 269 maize accessions with 43,737 single nucleotide polymorphisms (SNPs) to identify candidate genes and favorable alleles for controlling Cd accumulation in maize. Results When grown in contaminated soil, accessions varied significantly in leaf Cd concentration at both the seeding and maturing stages with phenotypic variation and the coefficient of variation all above 48%. The co-localized region between SYN27837 (147,034,650 bp) and SYN36598 (168,551,327 bp) on chromosome 2 was associated with leaf Cd under three soil conditions varying in Cd content in 2015 and 2016. The significant SNP (SYN25051) at position 161,275,547 could explained 27.1% of the phenotype variation. Through QTL mapping using the IBMSyn10 double haploid (DH) population, we validated the existence of a major QTL identified by GWAS; qLCd2 could explain the 39.8% average phenotype variation across the experiments. Expression of GRMZM2G175576 encoding a cadmium/zinc-transporting ATPase underlying the QTL was significantly increased in roots, stems and leaves of B73, a low Cd accumulation line in response to Cd stress. Conclusions Our findings provide new insights into the genetic control of Cd accumulation and could aid rapid development of maize genotypes with low-Cd accumulation by manipulation of the favorable alleles.

P1B-type ATPases, known as heavy metal ATPases (HMAs), play an important role in the control of cadmium (Cd) accumulation in plants. In this study, a total of 12 ZmHMA genes were identified in the maize genome and particularly classified into six clusters based on their phylogenetic relationship and motif compositions. Furthermore, the expression patterns of different ZmHMA genes varied with developmental stages, and were tissue specific under normal conditions. ZmHMA2 and ZmHMA3 genes exhibited significant up-regulation under Cd treatment. Eventually, the association analysis between 103 inbred lines and alleles in ZmHMA2 and ZmHMA3 revealed that one insertion–deletion (InDel) in the intron from ZmHMA2 was associated with leaf Cd concentration under low Cd condition at the seedling stage. Twenty polymorphisms in ZmHMA3 were significantly associated with leaf Cd concentration under various Cd levels at seedling and maturing stages. Five single nucleotide polymorphisms (SNPs) and two InDels of these significantly associated polymorphic loci from ZmHMA3 caused the amino acid substitutions and insertion or deletion events. Importantly, the proteins encoded by ZmHMA2 and ZmHMA3 genes were located in the plasma membrane. This comprehensive analysis will provide an important theoretical basis for future functional verification of ZmHMA genes to unravel the mechanisms of Cd accumulation in leaves of maize. Additionally, the favorable alleles in ZmHMA3 will lay a foundation for the marker-assisted selection of low Cd accumulation in maize.

Sorghum is an important grain, forage, and bioenergy crop. The objective of this study was to identify genetic signals associated with plant architecture and bioenergy traits in sorghum and sudangrass germplasm through a genome-wide association study (GWAS). Plant height (HT), tiller number (TN), internode number (IN), stem diameter (SD), panicle length (PL), panicle weight (PW), reducing sugar (RS) content, Brix, and protein (PRO) content were assessed in 300 germplasm consisting of grain sorghum, sweet sorghum, sudangrass, sweet sorghum-sweet sorghum recombinant inbred lines (RILs) and sudangrass-sudangrass RILs grown in three different environments over two years. Large variations of phenotypic traits were observed in the population panel. The heritability of traits were all higher than 0.5, ranging from 0.52 (PRO) to 0.92 (HT) with an average of 0.76. The population exhibited three population structures (Q) and minor relative kinship (K), assessed by using 7982 single-nucleotide polymorphisms (SNPs). After controlling Q and K, GWAS identified 24 SNPs that were significantly associated with traits, including three SNPs with HT, four with TN, four with PL, three with Brix, and ten with RS. Of them, seven SNPs were novel signals that were not identified previously, including one for HT, one for TN, one for Brix, and four for RS. The putative candidate genes involved in brassinosteroid regulatory pathway, auxin biosynthesis, carbohydrate metabolism, and sugar transport were identified underlying the significant SNPs. Identification of SNP signals and related candidate genes would enrich the current genomic resource for further molecular breeding aimed at improvement of food, feed, and biofuel productions of sorghum.

Switchgrass (Panicum virgatum) is a native prairie grass and valuable bio-energy crop. The physiological change from juvenile to reproductive adult can draw important resources away from growth into producing reproductive structures, thereby limiting the growth potential of early flowering plants. Delaying the flowering of switchgrass is one approach by which to increase total biomass. The objective of this research was to identify genetic variants and candidate genes for controlling heading and anthesis in segregating switchgrass populations. Four pseudo-F2 populations (two pairs of reciprocal crosses) were developed from lowland (late flowering) and upland (early flowering) ecotypes, and heading and anthesis dates of these populations were collected in Lafayette, IN and DeKalb, IL in 2015 and 2016. Across 2 years, there was a 34- and 73-day difference in heading and a 52- and 75-day difference in anthesis at the Lafayette and DeKalb locations, respectively. A total of 37,901 single nucleotide polymorphisms obtained by exome capture sequencing of the populations were used in a genome-wide association study (GWAS) that identified five significant signals at three loci for heading and two loci for anthesis. Among them, a homolog of FLOWERING LOCUS T on chromosome 5b associated with heading date was identified at the Lafayette location across 2 years. A homolog of ARABIDOPSIS PSEUDO-RESPONSE REGULATOR 5, a light modulator in the circadian clock associated with heading date was detected on chromosome 8a across locations and years. These results demonstrate that genetic variants related to floral development could lend themselves to a long-term goal of developing late flowering varieties of switchgrass with high biomass yield.