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Abstract Background The severity and frequency of drought are expected to increase substantially in the coming century and dramatically reduce crop yields. Manipulation of rhizosphere microbiomes is an emerging strategy for mitigating drought stress in agroecosystems. However, little is known about the mechanisms underlying how drought-resistant plant recruitment of specific rhizosphere fungi enhances drought adaptation of drought-sensitive wheats. Here, we investigated microbial community assembly features and functional profiles of rhizosphere microbiomes related to drought-resistant and drought-sensitive wheats by amplicon and shotgun metagenome sequencing techniques. We then established evident linkages between root morphology traits and putative keystone taxa based on microbial inoculation experiments. Furthermore, root RNA sequencing and RT-qPCR were employed to explore the mechanisms how rhizosphere microbes modify plant response traits to drought stresses. Results Our results indicated that host plant signature, plant niche compartment, and planting site jointly contribute to the variation of soil microbiome assembly and functional adaptation, with a relatively greater effect of host plant signature observed for the rhizosphere fungi community. Importantly, drought-resistant wheat (Yunhan 618) possessed more diverse bacterial and fungal taxa than that of the drought-sensitive wheat (Chinese Spring), particularly for specific fungal species. In terms of microbial interkingdom association networks, the drought-resistant variety possessed more complex microbial networks. Metagenomics analyses further suggested that the enriched rhizosphere microbiomes belonging to the drought-resistant cultivar had a higher investment in energy metabolism, particularly in carbon cycling, that shaped their distinctive drought tolerance via the mediation of drought-induced feedback functional pathways. Furthermore, we observed that host plant signature drives the differentiation in the ecological role of the cultivable fungal species Mortierella alpine (M. alpina) and Epicoccum nigrum (E. nigrum). The successful colonization of M. alpina on the root surface enhanced the resistance of wheats in response to drought stresses via activation of drought-responsive genes (e.g., CIPK9 and PP2C30). Notably, we found that lateral roots and root hairs were significantly suppressed by co-colonization of a drought-enriched fungus (M. alpina) and a drought-depleted fungus (E. nigrum). Conclusions Collectively, our findings revealed host genotypes profoundly influence rhizosphere microbiome assembly and functional adaptation, as well as it provides evidence that drought-resistant plant recruitment of specific rhizosphere fungi enhances drought tolerance of drought-sensitive wheats. These findings significantly underpin our understanding of the complex feedbacks between plants and microbes during drought, and lay a foundation for steering “beneficial keystone biome” to develop more resilient and productive crops under climate change. Video Abstract

Alveoli are an important part of the respiratory system whose function is to exchange oxygen and carbon dioxide molecules from the bloodstream. Maintaining the integrity and barrier function of the alveoli requires complex interactions of multiple cell lineages. Hence, comprehensive understanding of the biology of lung stem cells could improve the treatment of patients with lung disorders such as acute respiratory distress syndrome, fibrotic lung disease and cancer. This review focuses on recent progresses on mammalian alveolar stem cell subpopulations and PSC-derived lung models and discusses insights about the regeneration-specific cell status of alveolar stem cells. We also provide future directions for an improved understanding of post-injury lung repair processes and lung diseases.

Abstract Background The rhizosphere microbiome, which is shaped by host genotypes, root exudates, and plant domestication, is crucial for sustaining agricultural plant growth. Despite its importance, how plant domestication builds up specific rhizosphere microbiomes and metabolic functions, as well as the importance of these affected rhizobiomes and relevant root exudates in maintaining plant growth, is not well understood. Here, we firstly investigated the rhizosphere bacterial and fungal communities of domestication and wild accessions of tetraploid wheat using amplicon sequencing (16S and ITS) after 9 years of domestication process at the main production sites in China. We then explored the ecological roles of root exudation in shaping rhizosphere microbiome functions by integrating metagenomics and metabolic genomics approaches. Furthermore, we established evident linkages between root morphology traits and keystone taxa based on microbial culture and plant inoculation experiments. Results Our results suggested that plant rhizosphere microbiomes were co-shaped by both host genotypes and domestication status. The wheat genomes contributed more variation in the microbial diversity and composition of rhizosphere bacterial communities than fungal communities, whereas plant domestication status exerted much stronger influences on the fungal communities. In terms of microbial interkingdom association networks, domestication destabilized microbial network and depleted the abundance of keystone fungal taxa. Moreover, we found that domestication shifted the rhizosphere microbiome from slow growing and fungi dominated to fast growing and bacteria dominated, thereby resulting in a shift from fungi-dominated membership with enrichment of carbon fixation genes to bacteria-dominated membership with enrichment of carbon degradation genes. Metagenomics analyses further indicated that wild cultivars of wheat possess higher microbial function diversity than domesticated cultivars. Notably, we found that wild cultivar is able to harness rhizosphere microorganism carrying N transformation (i.e., nitrification, denitrification) and P mineralization pathway, whereas rhizobiomes carrying inorganic N fixation, organic N ammonification, and inorganic P solubilization genes are recruited by the releasing of root exudates from domesticated wheat. More importantly, our metabolite-wide association study indicated that the contrasting functional roles of root exudates and the harnessed keystone microbial taxa with different nutrient acquisition strategies jointly determined the aboveground plant phenotypes. Furthermore, we observed that although domesticated and wild wheats recruited distinct microbial taxa and relevant functions, domestication-induced recruitment of keystone taxa led to a consistent growth regulation of root regardless of wheat domestication status. Conclusions Our results indicate that plant domestication profoundly influences rhizosphere microbiome assembly and metabolic functions and provide evidence that host plants are able to harness a differentiated ecological role of root-associated keystone microbiomes through the release of root exudates to sustain belowground multi-nutrient cycles and plant growth. These findings provide valuable insights into the mechanisms underlying plant-microbiome interactions and how to harness the rhizosphere microbiome for crop improvement in sustainable agriculture. Video Abstract

Abstract As the number of turbines in offshore wind farms increases, so does the complexity of cable routing optimisation problems. Optimising the collector network is a crucial task for developers contributing between 15% and 30% of initial investment costs. For some algorithms, increasing the number of turbines leads to unfavourable scaling of the computational time and memory required to reach optimal solutions. Heuristics offer an alternative but are likely to incur increases in total costs relative to the optimal solution since heuristic searching cannot guarantee optimality. This study proposes a novel optimisation algorithm based on the ant‐colony heuristic by introducing decomposition techniques informed by the problem formulation to improve the computational performance. The new algorithm can reach near‐optimal solutions and requires little computational resource. Three algorithms are compared on a set of six case studies, including mixed‐integer linear programming (MILP), classical ant‐colony optimisation (ACO) algorithm, and the proposed ACO with decomposition, ACOsp. Optimal solutions were found using the MILP algorithm. ACO algorithm solutions cost 0.4–7.6% more than optimal solutions, whereas ACOsp solutions cost only 0.0–1.4% more than optimal solutions. The proposed ACOsp algorithm has shown to be a robust approach for large‐scale cable layout optimisation problems (>100 turbines) without requiring high‐performance computing facilities.

BackgroundSpontaneous intracerebral hemorrhage (SICH) is associated with high mortality and disability. Accurately predicting adverse prognostic risks of SICH is helpful in developing risk stratification and precision medicine strategies for this phenomenon.MethodsWe analyzed 413 patients with SICH admitted to Hefei Second People's Hospital as a training cohort, considering 74 patients from the First Affiliated Hospital of Anhui Medical University for external validation. Univariate and multivariate logistic regression analyses were used to select risk factors for 90-day functional outcomes, and a nomogram was developed to predict their incidence in patients. Discrimination, fitting performance, and clinical utility of the resulting nomogram were evaluated through receiver operating characteristic (ROC) curves, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), calibration plots, and decision curves analysis (DCA), respectively.ResultsOf the 413 patients, 180 had a poor prognosis. Univariate analysis showed significant variance of age, systolic pressure, intraventricular hemorrhage (IVH), Glasgow Coma Scale (GCS) scores, National Institute of Health Stroke Scale (NIHSS) scores, and hematoma volume between the groups (p < 0.05). Logistic multivariate regression analysis showed that age, IVH, NIHSS, and hematoma volume were associated with unfavorable outcomes. Based on the results, a nomogram model was developed with an area under the ROC curve of 0.91 (95% CI; 0.88–0.94) and 0.89 (95% CI; 0.80–0.95) in the training and validation sets, respectively. In the validation set, the accuracy, sensitivity, specificity, PPV, and NPV of the model were 0.851, 0.923, 0.812, 0.727, and 0.951, respectively. The calibration plot demonstrates the goodness of fit between the nomogram predictions and actual observations. Finally, DCA indicated significant clinical adaptability.ConclusionWe developed and validated a short-term prognostic nomogram model for patients with SICH including NIHSS scores, age, hematoma volume, and IVH. This model has valuable potential in predicting the prognosis of patients with SICH.

Abstract Background Brugada syndrome (Brs) and long QT syndrome (LQTs) are the most observed “inherited primary arrhythmia syndromes” and “channelopathies”, which lead to sudden cardiac death. Methods Detailed clinical information of Brs and LQTs patients was collected. Genomic DNA samples of peripheral blood were conducted for whole-exome sequencing on the Illumina HiSeq 2000 platform. Then, we performed bioinformatics analysis for 200 genes susceptible to arrhythmias and cardiomyopathies. Protein interaction and transcriptomic co-expression were analyzed using the online website and GTEx database. Results All sixteen cases of Brs and six cases of LQTs were enrolled in the current study. Four Brs carried known pathogenic or likely pathogenic of single-point mutations, including SCN5A p.R661W, SCN5A p.R965C, and KCNH2 p.R692Q. One Brs carried the heterozygous compound mutations of DSG2 p.F531C and SCN5A p.A1374S. Two Brs carried the novel heterozygous truncated mutations (MAF C). Three LQTs carried a single pathogenic mutation of SCN5A p.R1880H, KCNH2 p.D161N, and KCNQ1 p.R243S, respectively. One patient of LQTs carried a frameshift mutation of KCNH2 p. A188Gfs*143. Conclusions The truncated mutations of NEBL (p.R882X) and NPPA (p.R107X) may induce Brugada syndrome by abnormally affecting cardiac sodium channel. SCN5A (p.R661W, p.R965C and p.A1374S) and KCNH2 (p.R692Q) may cause Brugada syndrome, while SCN5A (p.R1880H), KCNQ1 (c.922-1G > C and p.R243S) and KCNH2 (p.D161N and p.A188Gfs*143) may lead to long QT syndrome.

In influenza vaccine development, Madin–Darby canine kidney (MDCK) cells provide multiple advantages, including large-scale production and egg independence. Several cell-based influenza vaccines have been approved worldwide. We cultured H5N1 virus in a serum-free MDCK cell suspension. The harvested virus was manufactured into vaccines after inactivation and purification. The vaccine effectiveness was assessed in the Wuhan Institute of Biological Products BSL2 facility. The pre- and postvaccination mouse serum titers were determined using the microneutralization and hemagglutination inhibition tests. The immunological responses induced by vaccine were investigated using immunological cell classification, cytokine expression quantification, and immunoglobulin G (IgG) subtype classification. The protective effect of the vaccine in mice was evaluated using challenge test. Antibodies against H5N1 in rats lasted up to 8 months after the first dose. Compared with those of the placebo group, the serum titer of vaccinated mice increased significantly, Th1 and Th2 cells were activated, and CD8+ T cells were activated in two dose groups. Furthermore, the challenge test showed that vaccination reduced the clinical symptoms and virus titer in the lungs of mice after challenge, indicating a superior immunological response. Notably, early after vaccination, considerably increased interferon-inducible protein-10 (IP-10) levels were found, indicating improved vaccine-induced innate immunity. However, IP-10 is an adverse event marker, which is a cause for concern. Overall, in the case of an outbreak, the whole-virion H5N1 vaccine should provide protection.

Myo-inositol and its derivatives play important roles in the tolerance of higher plants to abiotic stresses, and myo-inositol-1-phosphate synthase (MIPS) is the rate-limiting enzyme in myo-inositol biosynthesis. In this study, we found that increased myo-inositol biosynthesis enhanced drought tolerance in MdMIPS1-overexpressing apple lines under short-term progressive drought stress. The effect of myo-inositol appeared to be mediated by the increased accumulation of osmoprotectants such as glucose, sucrose, and proline, and by the increased activities of antioxidant enzymes that eliminate reactive oxygen species. Moreover, enhanced water-use efficiency (WUE) was observed in MdMIPS1-overexpressing apple lines under long-term moderate water deficit conditions that mimicked the water availability in the soil of the Loess Plateau. Enhanced WUE may have been associated with the synergistic regulation of osmotic balance and stomatal aperture mediated by increased myo-inositol biosynthesis. Taken together, our findings shed light on the positive effects of MdMIPS1-mediated myo-inositol biosynthesis on drought tolerance and WUE in apple.

Background Ischemic cardiovascular disease is the leading cause of death worldwide. Current pharmacologic therapy has multiple limitations, and patients remain symptomatic despite maximal medical therapies. Deficiency or inhibition of thymidine phosphorylase (TYMP) in mice reduces thrombosis, suggesting that TYMP could be a novel therapeutic target for patients with acute myocardial infarction (AMI). Methods and Results A mouse AMI model was established by ligation of the left anterior descending coronary artery in C57BL/6J wild‐type and TYMP‐deficient (Tymp−/−) mice. Cardiac function was monitored by echocardiography or Langendorff assay. TYMP‐deficient hearts had lower baseline contractility. However, cardiac function, systolic left ventricle anterior wall thickness, and diastolic wall strain were significantly greater 4 weeks after AMI compared with wild‐type hearts. TYMP deficiency reduced microthrombus formation after AMI. TYMP deficiency did not affect angiogenesis in either normal or infarcted myocardium but increased arteriogenesis post‐AMI. TYMP deficiency enhanced the mobilization of bone marrow stem cells and promoted mesenchymal stem cell (MSC) proliferation, migration, and resistance to inflammation and hypoxia. TYMP deficiency increased the number of larger MSCs and decreased matrix metalloproteinase‐2 expression, resulting in a high homing capability. TYMP deficiency induced constitutive AKT phosphorylation in MSCs but reduced expression of genes associated with retinoid‐interferon‐induced mortality‐19, a molecule that enhances cell death. Inhibition of TYMP with its selective inhibitor, tipiracil, phenocopied TYMP deficiency, improved post‐AMI cardiac function and systolic left ventricle anterior wall thickness, attenuated diastolic stiffness, and reduced infarct size. Conclusions This study demonstrated that TYMP plays an adverse role after AMI. Targeting TYMP may be a novel therapy for patients with AMI.

Abstract This study presents a new turbine layout optimisation approach using a grid‐based problem formulation for improved design performance and computational efficiency for industrial‐scale applications. A particle swarm optimisation algorithm is employed in the wind turbine layout optimisation, in which a micro‐siting function is proposed to allow solutions 50 m of deviation while maximising energy capture without compromising maritime navigation or search and rescue operations. Solutions are assessed by a wind farm model, comprising the Larsen wake model, a multiple wake effect summation method, and a rotor‐effective wind speed calculation. A novel look‐up function is populated by on‐the‐fly algorithm and is used to reduce the number of model evaluations by approximately 95%. A gigawatt scale hypothetical site is presented to test the model on a realistically complex scenario. A set of design solutions generated by the algorithm are compared to empirical designs, with the algorithm outperforming the empirical solutions by 7.55% on average, in terms of net‐present‐value of energy capture minus the capital cost of turbines. The numerical efficiency and design effectiveness are examined and further improvements discussed.

The carbonate gas reservoir of the fourth Member of Upper Sinian Dengying Formation (hereinafter referred as “Deng 4 Member”) is characterized by deep burial, high temperature, low porosity, low permeability and strong heterogeneity in the Gaoshiti-Moxi area of the central Sichuan Basin. In order to effectively enhance the well productivity and gas reservoir development benefits, this paper defines the reservoir stimulation factor by comprehensively considering the drilling, logging and well type characteristic parameters, to carry out quantitative reservoir evaluation. Then, the refined segmentation method was developed by fully considering the reservoir stimulation factor, in-situ stress and borehole condition. In addition, the differential acid fracturing technology was prepared for different types of reservoirs. On this basis, the specified staged acid fracturing technology of horizontal well for strong-heterogeneity carbonate reservoirs was developed and then applied in the field. And the following research results were obtained. First, the reservoir stimulation factor (y) can be used to accurately evaluate the reservoir characteristics. The high quality reservoir has y ≥ 1.0, the moderate reservoir has 0.5 ≤ y

A unique rotary kite turbine designed with tensile rotary power transmission (TRPT) is introduced in this work. Power extraction, power transmission and the ground station are modelled in a modular framework. The TRPT system is the key component of power transmission, for which three models with different levels of complexity are proposed. The first representation is based on the stationary state of the system, in which the external and internal torques of a TRPT section are in equilibrium, referred to as the steady-state TRPT model. The second representation is a simplified spring-disc model for dynamic TRPT, and the third one is a multi-spring model with higher degrees of freedom and more flexibility in describing TRPT dynamics. To assess the torque loss on TRPT, a simple tether drag model is written for the steady-state TRPT, followed by an improved tether drag model for the dynamic TRPT. This modular framework allows for multiple versions of the rotor, tether aerodynamics and TRPT representations. The developed models are validated by laboratory and field-testing experimental data, simulated over a range of modelling options. Model-based analysis are performed on TRPT design, rotor design and tether drag to understand any limitations and crucial design drivers. Improved designs are explored through multi-parameter optimisation based on steady-state analysis.

Shale gas is as an emerging industry and its development is highly concerned in China. Under the guidance and support of national industrial policies, shale gas industry develops rapidly and has already stepped into the stage of large-scale exploitation of shale gas buried less than 3500 m deep underground. In order to standardize the healthy and rapid development of shale gas industry, ensure available standards for the national supervision on shale gas exploration and development and quickly copy the technologies in the efficient exploration and development of shale gas, it is necessary to formulate the technical standards and technical standard system of the whole shale gas industry chain. In this paper, the current situations of shale gas exploration and development technologies in China were analyzed. Then the role and significance of the formulation of shale gas technical standards in promoting the progress of shale gas technologies were described in detail. Finally, the development direction of shale gas exploration technology and standard formulation was predicted. And the following research results were obtained. First, China has established the exploration and development theories and technical systems that are in line with national conditions, and 27 distinguished technologies of 6 technical series have been developed, including comprehensive geological evaluation of shale gas, development optimization, optimized and fast drilling of horizontal wells, stimulated reservoir volume of horizontal wells, factory-like operation, and distinguished, efficient and clean exploitation. Second, 173 distinguished shale gas standards have been formulated, and they provide a powerful support for the quality and fast development of China's shale gas industry. The annual output of shale gas in 2019 is 143.6 × 108 m3. In conclusion, the construction of shale gas technical standard system promotes the continuous improvement of shale gas exploration and development technologies, impels the significant upgrading of technical level and ensures the all-around HSE control.

Background The COVID-19 pandemic led to emergency measures to continue patient care and research at a comprehensive cancer center while protecting both employees and patients. Determining exposure and infection rates with SARS-CoV-2 were important to adjust workplace policies over time. Methods Dana-Farber Cancer Institute (DFCI) has over 7,000 employees. Participation was voluntary. After consent, participants completed questionnaire of demographics, exposures and risk factors for COVID-19 illness at each time point (baseline, 3, 6, and 12 months) along with blood draws for SARS-CoV-2 antibody testing. Primary measure was determination of titers of SARS-CoV-2 spike protein IgG over time. Results In total, 745 employees enrolled from May 2020 to February 2021 (mean [SD] age, 40[14] years; 572[80%] women). From May to July 2020, 47 of 519 employees (9.2%, 95% confidence interval [CI] 6.7–12.0%) tested positive for SARS-CoV-2 spike protein IgG antibodies. Three months later, 40 of 428 employees had positive antibodies (8.5%, 95% CI 6.0–11.0%) with 17 newly positive. At month 6, 78.5% of participants reported having received at least one dose of vaccine and the positivity rate for those vaccinated was 98% (95% CI, 95–100%). Spike protein IgG titers for those vaccinated were 7.9 times higher than participants not vaccinated (median IgG titer = 0.28 for positive antibody but not vaccinated versus 2.2 for vaccinated) but demonstrate evidence of waning over time. Conclusions SARS-CoV-2 antibody positivity remained less than 10% at a single comprehensive cancer center prior to vaccination and there is evidence of waning IgG titers over time after vaccination.

With coordinated charging and discharging, electric vehicles (EVs) in smart car parks can be used as energy storage systems and a reserve against unexpected outrage. In this work, a modeling and control framework for EVs in a smart car park has been built up, which includes key factors such as the charging and discharging costs, the battery degradation cost, the driving probability, the feed-in tariff (FIT), and the vehicle-to-grid (V2G) rebates. Each EVs' charging and discharging activities are scheduled through an optimization route with the purpose to minimize the car park electricity cost. Results from comprehensive simulation studies demonstrate the potential benefits of V2G for car park systems with multiple EVs subject to vehicle and battery characteristics, FIT and policy support.

Background: Cognitive decline leading to dementia, accompanied by the accumulation of amyloid-beta (Aβ) in neuritic plaques together with the appearance of neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (tau), are previously noted hallmarks of Alzheimer's disease (AD). We previously discovered hypervascularity in brain specimens from AD patients and consistent with this observation, we demonstrated that overexpression of Aβ drives cerebrovascular neoangiogenesis leading to hypervascularity and coincident tight-junction disruption and blood-brain barrier (BBB) leakiness in animal models of AD. We subsequently demonstrated that amyloid plaque burden and cerebrovascular pathogenesis subside when pro-angiogenic Aβ levels are reduced. Based on these data, we propose a paradigm of AD etiology where, as a compensatory response to impaired cerebral blood flow (CBF), Aβ triggers pathogenic cerebrovascular neoangiogenesis that underlies the conventional hallmarks of AD. Consequently, here we present evidence that repurposing anti-cancer drugs to modulate cerebrovascular neoangiogenesis, rather than directly targeting the amyloid cascade, may provide an effective treatment for AD and related vascular diseases of the brain. Methods: We explored whether the anti-cancer drug, Axitinib, a small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR) can inhibit aberrant cerebrovascular neoangiogenic changes, reduce Aβ deposits and reverse cognitive decline in an animal model of AD. One month post-treatment with Axitinib, we employed a battery of tests to assess cognition and memory in aged Tg2576 AD mice and used molecular analysis to demonstrate reduction of amyloid plaques, BBB leakage, hypervascularity and associated disease pathology. Findings: Targeting the pro-angiogenic pathway in AD using the cancer drug, Axitinib, dramatically reduced cerebrovascular neoangiogenesis, restored BBB integrity, resolved tight-junction pathogenesis, diminishes Aβ depositions in plaques and effectively restores memory and cognitive performance in a preclinical mouse model of AD. Interpretation: Modulation of neoangiogenesis, in an analogous approach to those used to treat aberrant vascularization in cancer and also in the wet form of age-related macular degeneration (AMD), provides an alternative therapeutic strategy for intervention in AD that warrants clinical investigation. Funding: None

The development of the Light Detection and Ranging (LIDAR) technology has enabled wider options for wind turbine control, in particular regarding disturbance rejection. The LIDAR measurements provide a spatial, preview wind information, based on which the controller has a better chance to cope with the wind disturbance before it affects the turbine operation. In this paper, a model predictive controller for above-rated wind turbine control was developed with the use of pseudo-LIDAR wind measurements data. A predictive control algorithm was developed based on a linearised wind turbine model, in which the disturbance from the incoming wind was computed by the LIDAR simulator. The optimal control action was applied to the nonlinear turbine model. The developed controller was compared with the baseline control and a previously developed LIDAR-assisted control combining a feedback-and-feedforward design. Our simulation studies on a 5 MW nonlinear wind turbine model, under different wind conditions, demonstrated that the developed LIDAR-based predictive control achieved improved performance in the presence of small variations in the out-of-plane rotor torque and fore-aft tower acceleration, as well as a smoother generator speed regulation and satisfied pitch activity control constraints.

Abstract Background Bladder cancer (BC) is a common type of cancer that involves tumors of the urinary system and poses a serious threat to human health. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNA biomarkers in BC urgently need to be investigated in regard to its function and regulatory mechanisms. Methods Identification of differentially expressed lncRNAs in BC tissue was performed via microarray analysis. To investigate the biological functions of LINC00612, loss-of-function and gain-of-function experiments were performed in vitro and in vivo. Bioinformatics analysis, dual-luciferase reporter assays, AGO2-RIP assays, RNA pull-down assays, real-time quantitative PCR (RT-qPCR) arrays, fluorescence in situ hybridization assays, and western blot assays were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). Results LINC00612 was upregulated in BC tissues and cell lines. Functionally, downregulation of LINC00612 inhibited cell proliferation and invasion in vitro and in vivo, whereas overexpression of LINC00612 resulted in the opposite effects. Bioinformatics analysis and luciferase assays revealed that miR-590 was a direct target of LINC0061, which was validated by dual-luciferase reporter assays, AGO2-RIP assays, RNA pull-down assays, RT-qPCR arrays, and rescue experiments. Additionally, miR-590 was shown to directly target the PHD finger protein 14 (PHF14) gene. LNIC00612 modulated the expression of E-cadherin and vimentin by competitively sponging miR-590 to elevate the expression of PHF14, thus affecting BC cellular epithelial-mesenchymal transition (EMT). Conclusions Our results indicate that LINC00612 enhances the proliferation and invasion ability of BC cells by sponging miR-590 to upregulate PHF14 expression and promote BC cellular EMT, suggesting that LINC00612 may act as a potential biomarker and therapeutic target for BC.

Well Wutan 1 is a wildcat well deployed in the Dazhou–Kaijiang paleo-uplift, eastern Sichuan Basin and its design depth is 7570 m. The Cambrian and Sinian strata are its main exploration targets, and the strata below the Silurian in this well are geologically uncertain with a high risk. A large section of gypsum-salt layer may be encountered in the Cambrian and the longitudinal pressure system is complex. It is predicted that the bottom hole temperature is up to 175 °C, and the bottom hole liquid column pressure exceeds 140 MPa, and there is hydrogen sulfide. As a result, the casing program design is confronted with great challenges. In this paper, the difficulties and risks of drilling engineering were analyzed. Then, a casing program was designed and optimized referring to the successful drilling experience of subsalt ultra-deep wells at home and abroad, combined with the pressure system characteristics of Well Wutan 1 and the creep performance of gypsum-salt layers. Finally, the casing program was applied on site. And the following research results were obtained. First, in order to prevent lost circulation, blowout and differential pressure induced stuck pipe in the open hole section, it is determined that the casing program shall be in the pattern of six-section casing with 5 setting points. Second, no setting point is needed in the Carboniferous pressure depleted reservoir for it is lithologically tight and differential pressure induced stuck pipe and lost circulation are less risky. Third, to better isolate the salt layer, one section of casing is specially designed for the Cambrian gypsum-salt layer and its collapse strength is 160 MPa to prevent collapse by salt creep. Fourth, Well Wutan 1 is drilled successfully to the expected strata and its total depth is 8060 m. In conclusion, the unconventional six-section casing program with 5 setting points to ensure the subsalt drilling safety in the eastern Sichuan Basin is rational. The successful drilling of Well Wutan 1 provides experiences and references for the follow-up exploration of deep-seated gas in the Dazhou–Kaijiang paleo-uplift. Keywords: Ultra-deep well, Complex pressure system, Gypsum-salt layer, Hydrogen sulfide bearing, Casing program, Sichuan basin, Eastern sichuan basin, Dazhou–kaijiang paleo-uplift, Well wutan 1

Objective: To compare the efficacy of traditional Chinese medicine (TCM) based on Zheng differentiation with angiotensin receptor blocker/angiotensin-converting enzyme inhibitor (ARB/ACEI) in treating diabetic kidney disease (DKD) from the aspects of decreasing urinary microalbumin, declining 24-h urinary protein, reducing endpoint events, and renal function protection. Methods: The Chinese Biomedical Literature Database (CBM), the Chinese Academy of Sciences database (CNKI), the VIP Chinese journal database, Wanfang DATA, Medline database, Cochrane library, excerpt medical database (Embase), and Web of science were used for literature searching. The reviewer manager 5.3 software was utilized to analyze the data. Results: Twenty-four studies including 1956 participants were involved in this review. Results showed that TCM had a better effect (mean difference [MD], −23.20, 95% confidence interval [CI], −30.60 to −15.79, P < 0.00001) than ARB/ACEI on lowering urinary albumin excretion rate (UAER) and urine albumin-to-creatinine ratio (MD −4.56 mg/mmol, 95% CI, −5.76 to −3.36, P < 0.00001). Moreover, the advantage of decreasing UAER was greater as the follow-up period become longer (P = 0.04). TCM also had a better effect in 24-h urinal protein, decreasing 0.36 g/24 h (95% CI, −0.45 to −0.27, P < 0.00001) more than the control in shorter follow-up period (ranged from 12 to 24 weeks) subgroup but only 0.08 g/24 h (95% CI, −0.13 to −0.03, P = 0.0006) in the longer follow-up period (>24 weeks) subgroup. TCM worked as well as ACEI/ARB in reducing endpoint events (relative risk, 0.67, 95% CI, 0.20–2.224, P = 0.51) and decreasing urinary albumin concentration (UAC) (MD, −16.50, 95% CI, −46.28–13.28, P = 0.28). As for protecting renal function, TCM had an equal effect to AECI/ARB in improving creatinine clearance ratio (MD, −3.30, 95% CI, −6.66–0.03, P = 0.05) or estimated glomerular filtration rate (MD, 1.00, 95% CI, −0.59–2.58, P = 0.22). However, TCM had a better effect in releasing the glomerular hyperfiltration state (MD, −9.64, 95% CI, −14.45 to −4.84, P < 0.0001). Conclusions: TCM based on Zheng differentiation can work as well as ACEI/ARB in treating DKD and even better in decreasing urinary microalbumin and releasing glomerular hyperfiltration. It is a good alternative treatment of DKD.

Drought has gradually become one of the most severe abiotic stresses on plants. Plants that experience stress training can exhibit enhanced stress tolerance. According to MicroRNA (miRNA) sequencing data, this study identified 195 candidate drought memory-related miRNAs in wheat, and targets of 64 (32.8%) candidate miRNAs were validated by degradome sequencing. Several drought memory-related miRNAs such as tae-miR9676-5p, tae-MIR9676-p3_1ss21GA, tae-miR171a, tae-miR531_L-2, tae-miR408_L-1, PC-3p-5049_3565, tae-miR396c-5p, tae-miR9778, tae-miR164a-5p, and tae-miR9662a-3p were validated as having a strong response to drought memory by regulating the expression of their target genes. In addition, overexpression of drought memory-related miRNA, tae-miR531_L-2, can remarkably improve the drought tolerance of transgenic Arabidopsisthaliana. Drought memory can regulate plant cellular signal transduction, plant biosynthetic processes, and other biological processes to cope with drought via transcriptional memory. In addition, drought memory-related miRNAs can promote starch and sucrose catabolism and soluble sugar accumulation and regulate proline homeostasis to improve plant drought resistance. Our results could contribute to an understanding of drought memory in wheat seedlings and may provide a new strategy for drought-resistant breeding.

HIV patients have an increased risk of developing non-AIDS-defining cancers but the molecular mechanisms underlying this predisposition are unclear. Here the authors show that exosomes secreted by HIV-infected T cells or isolated from the blood of HIV-positive patients, stimulate oncogenic properties of cancer cells through the activation of ERK1/2 signaling pathway.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), is a human respiratory disease. Hitherto, there is no effective treatment has been established. Patients with cardiovascular or diabetes comorbidities are a high-risk cohort. COVID-19 is accompanied by excessive systemic thrombotic events, but the mechanism is not yet known. Recent studies have indicated that thymidine phosphorylase (TYMP) plays an important role in platelet activation, thrombosis, and TYMP expression is increased in diabetic patients. By using data provided by the MGH (Massachusetts General Hospital) Emergency Department COVID-19 Cohort with Olink Proteomics, here we show that plasma TYMP level is correlated with the COVID-19 associated thrombotic event, inflammation, and organ damage, as evidenced by the positive correlations with plasma D-dimer, CRP (C reactive protein), and LDH (lactate dehydrogenase), as well as Interferons (IFN). Plasma TYMP is also positively correlated with COVID-19 patients who had respiratory symptoms. TYMP thus could be an acuity marker for COVID-19 diagnosis. Targeting TYMP with tipiracil, a selective TYMP inhibitor, which has been approved by the Food and Drug Administration for clinical use, could be a novel effective medicine for COVID-19.

The implementation of horizontal wells is a key to economic development of the deep shale gas reservoir. In order to optimize the key parameters for drilling, stimulation, and the production system, the development effect of a horizontal well in deep shale gas formations was investigated from various aspects in this study. The drilling, fracturing, and production performances of this well were analyzed combining with the geological characteristics. The main technical problems and key factors that restrict the gas well performance and estimated ultimate recovery (EUR) were clarified. Through the integrated study of geology and engineering, the optimization strategies for increasing gas production and EUR are provided. The Z2 area, where the Z2-H1 well is located, has good reservoir physical properties, which bring a high drilling efficiency. However, there are still some problems during its development, such as poor fracture extension both horizontally and vertically, limited stimulated reservoir volume (SRV), rapid production declining, large water production, and serious liquid accumulation. In this study, a comprehensive approach was proposed that can improve single-well production and EUR by optimizing the target position, horizontal section length, pathway, spacing, new drilling and fracturing technology, and production system.

According to the current situation of knowledge popularization, students simply rely on the knowledge learned in the classroom that is far from adapting to the development of modern society; so, every student needs to have the consciousness and ability of independent learning. The research of the English self-help learning system based on partial differential equation method comes into being with information network technology as the foundation for survival and development. The existing partial differential equation recognition models based on average curvature motion are all edge-based and need to use the external force defined by the image gradient to attract the zero level set (evolution curve) to move to the target edge and finally stay on the target edge. Therefore, it is difficult to obtain ideal results when extracting fuzzy or discrete boundaries (perceptual boundaries), and it is very sensitive to the selection of initial contour and noise. To solve this problem, this paper proposes a new recognition model of partial differential equations based on mean curvature motion. This overcomes some defects of existing edge models because it is region-based and does not require image gradient as a condition to stop evolution. The proposed model can avoid manual initial curve selection and allow stopping conditions to be set in the algorithm. In addition, in the numerical solution of partial differential equations, the existing model uses upwind difference scheme, and the semi-implicit additive operator separation method is adopted in this paper. Some other layers are added, and some hyperparameters are adjusted when the convolutional neural networks of inception PDEs are constructed by stacking the structure of inception PDEs. In the contrast experiment with the prototype, the software and hardware environment are the same, and the input is exactly the same. For the handwritten English alphabet data set, the variant structure can obtain more than 90% of the training accuracy and verification accuracy, which is better than the experimental accuracy of the prototype. In addition, because the inception PDE structure contains fewer parameters than the prototype, it is more computationally efficient and takes less training time per batch than the prototype.

Autophagy is an indispensable biological process and plays crucial roles in plant growth and plant responses to both biotic and abiotic stresses. This study systematically identified autophagy-related proteins (ATGs) in wheat and its diploid and tetraploid progenitors and investigated their genomic organization, structure characteristics, expression patterns, genetic variation, and regulation network. We identified a total of 77, 51, 29, and 30 ATGs in wheat, wild emmer, T. urartu and A. tauschii, respectively, and grouped them into 19 subfamilies. We found that these autophagy-related genes (ATGs) suffered various degrees of selection during the wheat’s domestication and breeding processes. The genetic variations in the promoter region of Ta2A_ATG8a were associated with differences in seed size, which might be artificially selected for during the domestication process of tetraploid wheat. Overexpression of TaVAMP727 improved the cold, drought, and salt stresses resistance of the transgenic Arabidopsis and wheat. It also promoted wheat heading by regulating the expression of most ATGs. Our findings demonstrate how ATGs regulate wheat plant development and improve abiotic stress resistance. The results presented here provide the basis for wheat breeding programs for selecting varieties of higher yield which are capable of growing in colder, drier, and saltier areas.

The Lower Cambrian Longwangmiao dolomite gas reservoirs in the Sichuan Basin are characterized by well-developed natural micro-fractures and dissolved pores and cavities. Due to the strong heterogeneity of reservoirs and the serious damage of drilling and completion fluids, acid placement is difficult, and especially the acidizing stimulation of long-interval highly deviated wells or horizontal wells is more difficult. In this paper, the diverting mechanism and rheological behavior of viscoelastic surfactant (VES) based diverting acid was firstly investigated, and the diverting acid with good diversion performance and low secondary damage was selected as the main acid. Then, based on the experimental results of its rheological behaviors, an empirical model of effective viscosity was fitted and a two-scale wormhole propagation model was coupled. And accordingly, a mathematical model for the acidizing of self-diverting acid was established to simulate the pH value, Ca2+ concentration, effective viscosity and wormhole shape under the effect of diverting acid in long-interval highly deviated wells that are non-uniformly damaged. Finally, gelled acid and 5% VES diverting acid were compared in terms of their etched wormhole shapes, flow rate distribution and acid imbibition profiles. It is shown that the diverting acid can obviously improve the acid imbibition profile of strong-heterogeneity reservoirs to intensify low-permeability reservoir stimulation. In view of the strong heterogeneity of Longwangmiao dolomite reservoirs and the complexities of drilling and completion fluid damage in the Sichuan Basin, a placement technology was developed for variable VES concentration diverting acid in horizontal wells and long-interval highly deviated wells completed with slotted liners. This acid placement technology has been practically applied in 8 wells and their cumulative gas production rate tested at the wellhead is 1233.46 × 104 m3/d. The average production stimulation ratio per well is up to 1.95. It provides a support for the efficient development of the Longwangmiao giant gas reservoir. Keywords: Sichuan Basin, Early Cambrian, Longwangmiao Fm gas reservoir, Dolomite, Diverting acid, Rheological behavior, Matrix acidizing, Numerical simulation, Field application, Highly-efficient development

Multipath is one of the dominant error sources for high-precision positioning systems, such as global navigation satellite systems. The minimum mean square error criterion is usually employed for multipath estimation under the assumption of Gaussian noise. For non-Gaussian noise as appeared in most practical applications, alternative solutions are required for multipath estimation. In this paper, a multipath estimation algorithm is proposed based on the minimum error entropy (MEE) criterion under Gaussian or non-Gaussian noises. A key advantage of using MEE is that it can minimize the randomness of error signals; however, the shift-invariance characteristics in MEE may lead to a bias of the estimation result. To mitigate such a bias, an improved estimation strategy is proposed by integrating the second-order central moment of the estimation error together with the prior information of multipath parameters as a constraint. The multipath estimation problem is thus formulated as a constrained optimization problem. A modified ε-constrained rank-based differential evolution (εRDE) algorithm is developed to find the optimal solution. The effectiveness of the proposed algorithm, in terms of reducing the multipath estimation error and minimizing the randomness in the error signal, has been examined through case studies with Gaussian and non-Gaussian noises.

Plant proline-rich proteins (PRPs) are cell wall proteins that occur in the plant kingdom and are involved in plant development and stress response. In this study, 9 PRP genes were identified from the apple genome and a comprehensive analysis of the PRP family was conducted, including gene structures, phylogenetic analysis, chromosome mapping, and so on. The expression of MdPRPs varied among tissues and in response to different types of stresses. MdPRP4 and MdPRP7 were induced by five detected stress treatments, including heat, drought, abscisic acid, cold, and salt; the expression patterns of the others varied under different types of stress. Subcellular localization showed that MdPRPs mainly functioned in the cytoplasm, except for MdPRP1 and MdPRP5, which also functioned in the nucleus. When MdPRP6 was overexpressed in tobacco, the transgenic plants showed higher tolerance to high temperature (48 °C) compared with wild-type (WT) plants. The transgenic plants showed milder wilting, a lower accumulation of electrolyte leakage, MDA and ROS, and a higher level of chlorophyll and SOD and POD activity, indicating that MdPRP6 may be an important gene in apples for heat stress tolerance. Overall, this study suggested that MdPRPs are critically important for the ability of apple responses to stresses.

The combination of the ionic liquid co-lyophilized lipase and microwave irradiation was used to improve enzyme performance in enantioselective esterification of α-lipoic acid. Effects of various reaction conditions on enzyme activity and enantioselectivity were investigated. Under optimal condition, the highest enantioselectivity (E = 41.2) was observed with a high enzyme activity (178.1 μmol/h/mg) when using the ionic liquid co-lyophilized lipase with microwave assistance. Furthermore, the ionic liquid co-lyophilized lipase exhibited excellent reusability under low power microwave.