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Abstract The offshore wind farms are the main trend of the wind power development in the future. The medium frequency diode rectifier unit based high voltage direct current transmission system is proposed here for offshore wind farm integration. Unlike conventional high voltage direct current solutions, the rated frequency of the offshore alternating current (AC) grid is increased to about 100∼400 Hz in the proposed system. Besides, a grid‐forming control scheme for the wind turbine converters is also proposed in this paper, where the machine side converter controls the direct current (DC) voltage and the grid side converter controls its output alternating current voltage in the global unified reference coordinate system. As a result, smaller and lighter passive components, such as the transformers, alternating current filters and reactive power (VAR) compensators, could be adopted in the offshore grid, which is beneficial for achieving higher economic efficiency. The small stability analysis and the time domain simulation of the proposed system are carried out based on a simplified model and power systems computer aided design/electromagnetic transients including DC (PSCAD/EMTDC) respectively, and the feasibility of the proposed schemes is verified.

Abstract Introduction Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure. Materials and methods All 154 patients with COVID-19 were recruited from the Second People’s Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study. Results There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge. Conclusion Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.

Abstract The advantages, such as the mature control method, less volume of the converter and generator, make the doubly fed induction generator system prevalent in the wind power industry. Nevertheless, the doubly fed induction generator is more susceptible to grid faults and disturbances. The instantaneous high voltage fault may occur due to the excessive local reactive power after the doubly fed induction generator system achieving low voltage ride through, and then the wind turbine might be disconnected again. Hence, not only the low voltage ride through but also high voltage ride through capability should be required for the doubly fed induction generator system to meet the grid code requirements. A comprehensive review of the state of the art low voltage ride through and high voltage ride through technologies for the doubly fed induction generator system is presented. Firstly, different types of common low voltage ride through and high voltage ride through techniques are classified according to their features, i.e. auxiliary hardware, linear or nonlinear control strategies etc. The pros and cons of different low voltage ride through and high voltage ride through techniques are given. Furthermore, the latest developments of low voltage ride through and high voltage ride through technologies are introduced. Finally, the future trends of both the low voltage ride through and high voltage ride through technologies are discussed.

Previously we have reported a specific hydrolysate form of silk fibroin named SFH and in vitro beneficial effects of SFH on neuron, however, evidence in vivo for the specific neuroprotective function of SFH on AD is urgently needed and our understanding for mechanism underlying SFH function is far from completion. In this study, we report here the amelioration of neurodegenerative changes in Aβ25-35-induced rat models of AD by SFH. We found that SFH in vivo significantly attenuated impairment of spatial learning and memory, prevented neuronal damages and decreased multisite tau hyperphosphorylation induced by Aβ25-35. In vivo and in vitro results also further indicated that the beneficial effect of SFH on AD may be due to its interference with microglia-mediated neuroinflammation. SFH can inhibit abnormal activation of microglial and expressions of proinflammatory mediators in Aβ25-35-induced rat and rat primary microglia models can be inhibited by SFH via MAPKs /NF-κB signaling pathway.

Bordetella pertussis is the most frequent causative agent for pertussis, which is a highly contagious disease. Here, we developed a method based on loop-mediated isothermal amplification (LAMP) and nanoparticle-based lateral flow biosensor (LFB) for the timely diagnosis of B. pertussis infections. A set of six primers was designed for LAMP reactions, and the LAMP results were rapidly and visually indicated using LFB. The recommended condition for the B. pertussis LAMP reactions is 40 min at 66°C. Our results confirmed that the LAMP-LFB assay could specifically detect B. pertussis and did not cross-react with non-B. pertussis isolates. The sensitivity of the B. pertussis LAMP-LFB assay was 50 fg per reaction. In particular, 108 nasopharyngeal swab (NPS) samples were collected to evaluate the B. pertussis LAMP-LFB assay, and the results were compared with those of the quantitative PCR (qPCR) method. The positive rates of B. pertussis LAMP-LFB and qPCR were 40.7% and 38.8%, respectively, and the agreement between the LAMP-LFB and qPCR results was 98%, with a kappa value of 0.96. The whole process of LAMP-LFB can be completed within 1 h, which is much shorter than that of qPCR, including about 15 min of rapid DNA extraction, 40 min of LAMP reaction, and within 2 min of the LFB test. Collectively, the B. pertussis LAMP-LFB assay developed in this report offers a new option for the rapid, reliable, and simple diagnosis of B. pertussis infections.

The series line-commutated converter (LCC) and modular multilevel converter (MMC) hybrid HVDC system provides a more economical and flexible alternative for UHVDC transmission. With the LCC DC voltage reduction, no current cut-off will occur under slight rectifier-side AC faults. However, with the limitation of the MMC voltage modulation ratio, when the rectifier-side AC fault is extremely acute, the current cut-off will unavoidably exist, resulting in enormous impacts on AC and DC systems. To reduce the risk of the current cut-off and improve fault recovery, this paper proposes an enhanced coordinated control strategy. First, under the varying severity of rectifier-side AC faults, the $U$ - $I$ operation characteristics are meticulously analyzed. Then, the third harmonic voltage injection (THVI) and reactive power dynamic adjustment (RPDA) are introduced to expand the operation range of MMC DC voltage. Based on the enlarged operation range, a backup DC current control of MMC is proposed to adaptively regulate the MMC DC voltage relying on the fault severity. Finally, the feasibility and effectiveness of the proposed coordinated control strategy is verified through several simulation scenarios of varied fault severity on PSCAD/EMTDC. The simulation results show that, the proposed control enlarges the system operation range, improves the fault recovery, and significantly reduces the risk of current cut-off.

Uncontrolled bleeding and infection can cause significant increases in mortalities. Hydrogel sealants have attracted extensive attention for their ability to control bleeding. However, because interfacial water is a formidable barrier to strong surface bonding, a challenge remains in finding a product that offers robust tissue adhesion combined with anti-infection properties. Inspired by the strong adhesive mechanism of biofilm and mussels, we report a novel dual bionic adhesive hydrogel (DBAH) based on chitosan grafted with methacrylate (CS-MA), dopamine (DA), and N-hydroxymethyl acrylamide (NMA) via a facile radical polymerization process. CS-MA and DA were simultaneously included in the adhesive polymer for imitating the two key adhesive components: polysaccharide intercellular adhesin (PIA) of staphylococci biofilm and 3,4-dihydroxy-l-phenylalanine (Dopa) of mussel foot protein, respectively. DBAH presented strong adhesion at 34 kPa even upon three cycles of full immersion in water and was able to withstand up to 168 mm Hg blood pressure, which is significantly higher than the 60–160 mm Hg measured in most clinical settings. Most importantly, these hydrogels presented outstanding hemostatic capability under wet and dynamic in vivo movements while displaying excellent antibacterial properties and biocompatibility. Therefore, DBAH represents a promising class of biomaterials for high-efficiency hemostasis and wound healing.

Abstract Background Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers. Methods We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity. Results FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion. Conclusions Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

The calculation of the main circuit parameters is the basic part of the engineering design for high voltage direct current (HVDC) transmission systems. Compared to the conventional line commutated converter (LCC), the application of the capacitor commutated converter (CCC) can reduce the probability of commutation failures and the shunt capacitor reactive compensation. This paper proposes a calculation method of main circuit parameters for the CCC-based HVDC system. Firstly, the topology of a CCC-HVDC transmission system is described. Secondly, based on the steady-state mathematical model of the CCC, the paper proposes the calculation method of the commutation capacitor to satisfy the system requirements, and the calculation formulas of the main circuit parameters are also given. Then the calculation procedure of the main circuit steady-state parameters is described in detail considering system parameters, control modes, calculation tolerances and operating conditions. Finally, a two-terminal ±500 kV/3000 MW LCC-CCC HVDC transmission system is presented to verify the validity of the main circuit parameter calculation method. The proposed method has great significance for the AC filter design in practical engineering application.

Focusing on the three technical features related to the offshore wind turbine and the offshore transmission channel, eight schemes of offshore wind power transmission and their corresponding key technologies are discussed. The first technical feature describes the grid-forming capability of the offshore wind turbine; two types of wind turbines are discussed, namely, the grid-following wind turbine and the grid-forming wind turbine. The second technical feature describes the frequency characteristics of the output voltage and current of the offshore wind turbine, including DC, low-frequency AC, power-frequency AC and medium-frequency AC. The third technical feature describes the power transmission modes adopted by the offshore high-voltage main transmission channel, which are HVDC, high-voltage low-frequency AC and high-voltage power-frequency AC. Finally, the technical characteristics and maturity of the eight offshore wind power transmission schemes are reviewed, and a technical development direction is recommended.

Porcine reproductive and respiratory syndrome (PRRS) is a vertically transmitted reproductive disorder that is typically characterized by miscarriage, premature birth, and stillbirth in pregnant sows after infection. Such characteristics indicate that PRRSV can infect and penetrate the porcine placental barrier to infect fetus piglets. The porcine trophoblast is an important component of the placental barrier, and secretes various hormones, including estrogen and progesterone, to maintain normal pregnancy and embryonic development during pregnancy. It is conceivable that the pathogenic effects of PRRSV infection on porcine trophoblast cells may lead to reproductive failure; however, the underlying detailed mechanism of the interaction between porcine trophoblast (PTR2) cells and PRRSV is unknown. Therefore, we conducted genome-wide mRNA and long non-coding RNA (lncRNA) analysis profiling in PRRSV-infected PTR2. The results showed that 672 mRNAs and 476 lncRNAs were significantly different from the control group after viral infection. Target genes of the co-expression and co-location of differential mRNAs and lncRNAs were enriched by GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, revealing that most of the pathways were involved in cell nutrient metabolism, cell proliferation, and differentiation. Specifically, the estrogen signaling pathway, the PI3K (PhosphoInositide-3 Kinase)-Akt (serine/threonine kinase) signaling pathway, and the insulin secretion related to embryonic development were selected for analysis. Further research found that PRRSV inhibits the expression of G-protein-coupled estrogen receptor 1 (GPER1), thereby reducing estrogen-induced phosphorylation of AKT and the mammalian target of rapamycin (mTOR). The reduction in the phosphorylation of AKT and mTOR blocks the activation of the GPER1- PI3K-AKT-mTOR signaling pathway, consequently restraining insulin secretion, impacting PTR2 cell proliferation, differentiation, and nutrient metabolism. We also found that PRRSV triggered trophoblast cell apoptosis, interrupting the integrity of the placental villus barrier. Furthermore, the interaction network diagram of lncRNA, regulating GPER1 and apoptosis-related genes, was constructed, providing a reference for enriching the functions of these lncRNA in the future. In summary, this article elucidated the differential expression of mRNA and lncRNA in trophoblast cells infected with PRRSV. This infection could inhibit the PI3K-AKT-mTOR pathway and trigger apoptosis, providing insight into the mechanism of the vertical transmission of PRRSV and the manifestation of reproductive failure.

Renal cell carcinoma (RCC) originates from the epithelial cells of the renal tubules and has a high degree of malignancy and heterogeneity. Recent studies have found that exosomes regulate intercellular communication via transferring various bioactive molecules, such as circular RNAs (circRNAs), which are critical for cancer progression. However, the role of tumor cell-derived exosomal circRNAs in RCC remains unclear. In this study, we reported the high expression of circ-PRKCI in RCC tissues and serum exosomes. We also found that circ-PRKCI could be transferred exosomally from highly malignant RCC cells to relatively less malignant RCC cells. Tumor cell-derived exosomal circ-PRKCI promoted the proliferation, migration, and invasion of RCC cells, while inhibiting their apoptosis. Mechanistically, we found that circ-PRKCI promoted the proliferation of RCC via the miR-545-3p/CCND1 signaling pathway. Our study is the first to report the potential mechanisms of tumor cell-derived exosomal circ-PRKCI in RCC. In conclusion, this study will provide a new understanding about the molecular mechanisms of RCC progression.

Since its first appearance in April 2021, B.1.617.2, also termed variant Delta, catalyzed one major worldwide wave dominating the second year of coronavirus disease 2019 (COVID-19) pandemic. Despite its quick disappearance worldwide, the strong virulence caused by a few point mutations remains an unsolved problem largely. Along with the other two sublineages, the Delta variant harbors an accumulation of Spike protein mutations, including the previously identified L452R, E484Q, and the newly emerged T478K on its receptor binding domain (RBD). We used molecular dynamics (MD) simulations, in combination with free energy perturbation (FEP) calculations, to examine the effects of two combinative mutation sets, L452R + E484Q and L452R + T478K. Our dynamic trajectories reveal an enhancement in binding affinity between mutated RBD and the common receptor protein angiotensin converting enzyme 2 (ACE2) through a net increase in the buried molecular surface area of the binary complex. This enhanced binding, mediated through Gln493, sets the same stage for all three sublineages due to the presence of L452R mutation. The other mutation component, E484Q or T478K, was found to impact the RBD-ACE2 binding and help the variant to evade several monoclonal antibodies (mAbs) in a distinct manner. Especially for L452R + T478K, synergies between mutations are mediated through a complex residual and water interaction network and further enhance its binding to ACE2. Taking together, this study demonstrates that new variants of SARS-CoV-2 accomplish both “attack” (infection) and “defense” (antibody neutralization escape) with the same “polished sword” (mutated Spike RBD).

Abstract Background Obesity contributes to high cancer risk in humans and the mechanistic links between these two pathologies are not yet understood. Recent emerging evidence has associated obesity and cancer with metabolic abnormalities and inflammation where microRNA regulation has a strong implication. Methods In this study, we have developed an integrated framework to unravel obesity-cancer linkage from a microRNA regulation perspective. Different from traditional means of identifying static microRNA targets based on sequence and structure properties, our approach focused on the discovery of context-dependent microRNA-mRNA interactions that are potentially associated with disease progression via large-scale genomic analysis. Specifically, a meta-regression analysis and the integration of multi-omics information from obesity and cancers were presented to investigate the microRNA regulation in a dynamic and systematic manner. Results Our analysis has identified a total number of 2,143 unique microRNA-gene interactions in obesity and seven types of cancer. Common interactions in obesity and obesity-associated cancers are found to regulate genes in key metabolic processes such as fatty acid and arachidonic acid metabolism and various signaling pathways related to cell growth and inflammation. Additionally, modulated co-regulations among microRNAs targeting the same functional processes were reflected through the analysis. Conclusion We demonstrated the statistical modeling of microRNA-mediated gene regulation can facilitate the association study between obesity and cancer. The entire framework provides a powerful tool to understand multifaceted gene regulation in complex human diseases that can be generalized in other biomedical applications.

Entrepreneurship plays an important role in the development of national economy. The study aims to accelerate the construction of social and economic structure by improving the success rate of new entrepreneurs in the process of innovation and entrepreneurship. First, the related theories of financial risk prediction are introduced, and entrepreneurial psychological status and the psychological states on entrepreneurship are analyzed. Second, the current situation of entrepreneurial psychology of new entrepreneurs is analyzed through a questionnaire survey and model test. The results show that private enterprises account for the largest proportion, with a percentage of 58.14% of 125. In total, 32 Chinese-foreign joint ventures rank second and account for 14.88% of the total, and the scale of each type of enterprises accounts for 25%, respectively. The operating years of enterprises are mainly between 10 and 20 years. Among the enterprises surveyed, the significant level of entrepreneurial psychology and entrepreneurial opportunity of entrepreneurs is p = 0.000–0.01. It indicates that males’ psychological adjustment ability and entrepreneurial ability in the entrepreneurial process are higher than females’, and their entrepreneurial psychological states and entrepreneurial ability will improve with the growth of age, education levels, and positions. It is concluded that entrepreneurial psychological capital and entrepreneurial opportunity are significantly positively correlated with financial risk expectation. The research results prove the impact of financial risks on the entrepreneurial psychology of new entrepreneurs, and provide a reference for new entrepreneurs in predicting financial risks.

Implantable brain electrophysiology electrodes are valuable tools in both fundamental and applied neuroscience due to their ability to record neural activity with high spatiotemporal resolution from shallow and deep brain regions. Their use has been hindered, however, by the challenges in achieving chronically stable operations. Furthermore, implantable depth neural electrodes can only carry out limited data sampling within predefined anatomical regions, making it challenging to perform large-area brain mapping. Minimizing inflammatory responses and associated gliosis formation, and improving the durability and stability of the electrode insulation layers are critical to achieve long-term stable neural recording and stimulation. Combining electrophysiological measurements with simultaneous whole-brain imaging techniques, such as magnetic resonance imaging (MRI), provides a useful solution to alleviate the challenge in scalability of implantable depth electrodes. In recent years, various carbon-based materials have been used to fabricate flexible neural depth electrodes with reduced inflammatory responses and MRI-compatible electrodes, which allows structural and functional MRI mapping of the whole brain without obstructing any brain regions around the electrodes. Here, we conducted a systematic comparative evaluation on the electrochemical properties, mechanical properties, and MRI compatibility of different kinds of carbon-based fiber materials, including carbon nanotube fibers, graphene fibers, and carbon fibers. We also developed a strategy to improve the stability of the electrode insulation without sacrificing the flexibility of the implantable depth electrodes by sandwiching an inorganic barrier layer inside the polymer insulation film. These studies provide us with important insights into choosing the most suitable materials for next-generation implantable depth electrodes with unique capabilities for applications in both fundamental and translational neuroscience research.

Abstract This review will synthesize the results from publications focused on homework time and academic performance, and estimate the relationship between the two. Our objectives are: (1) To identify the extent of the relationship between homework time and students' academic performance; (2) To analyze the differences in the effectiveness of homework time across genders, grades, subject and regions; and (3) To identify the potential factors that affect homework time, such as academic subject, task difficulty, type of homework, mode of homework, parental involvement, and feedback on homework.

BackgroundResistin is an endogenous ligand of Toll-like receptor 4 that activates several inflammatory signals. But the physiological function of resistin in community-acquired pneumonia (CAP) remains unknown. The goal of this research was to explore the associations between serum resistin and the severity and prognosis in CAP patients through a retrospective cohort study.MethodsAll 212 CAP patients and 106 healthy cases were enrolled. Demographic characteristics were extracted. Serum resistin was determined via enzyme-linked immunosorbent assay. The prognosis was tracked in CAP patients.ResultsSerum resistin on admission was raised in CAP patients compared with control cases. The level of resistin was gradually increased in parallel with CAP severity scores in CAP patients. Pearson and Spearman analyses revealed that serum resistin was positively correlated with CAP severity scores, white blood cells, urea nitrogen, creatinine, and inflammatory cytokines among CAP patients. There were negative relationships between resistin and hematocrit and albumin in CAP patients. Besides, linear and logistic regression analyses further indicated that serum resistin on admission was positively associated with CAP severity scores among CAP patients. Follow-up research revealed that serum resistin elevation on admission prolonged hospital stay in CAP patients.ConclusionSerum resistin on admission is positively correlated with the severity and hospital stay in CAP patients, indicating that resistin may be involved in the physiological process of CAP. Serum resistin may be a potential biomarker in the diagnosis and prognosis for CAP.

ABSTRACT Background: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. Materials and Methods: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR−), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. Results: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR−, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. Conclusions: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.

Abstract Background The glyoxylate reductase (GR) multigene family has been described in various plant species, their isoforms show different biochemical features in plants. However, few studies have addressed the biological roles of GR isozymes, especially for rice. Results Here, we report a detailed analysis of the enzymatic properties and physiological roles of OsGR1 and OsGR2 in rice. The results showed that both enzymes prefer NADPH to NADH as cofactor, and the NADPH-dependent glyoxylate reducing activity represents the major GR activity in various tissues and at different growth stages; and OsGR1 proteins were more abundant than OsGR2, which is also a major contributor to total GR activities. By generating and characterizing various OsGR-genetically modified rice lines, including overexpression, single and double-knockout lines, we found that no phenotypic differences occur among the various transgenic lines under normal growth conditions, while a dwarfish growth phenotype was noticed under photorespiration-promoted conditions. Conclusion Our results suggest that OsGR1 and OsGR2, with distinct enzymatic characteristics, function redundantly in detoxifying glyoxylate in rice plants under normal growth conditions, whereas both are simultaneously required under high photorespiration conditions.

Abstract Background Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs. Methods The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Results In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs. Conclusion This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

Catalytic asymmetric hydrosilylation of internal alkenes has proven elusive due to more favourable double bond reduction or isomerization. Here, the authors show an enantioselective Si-C coupling by hydrosilylation of activated alkenes using a palladium/phosphoramidite catalyst affording axially chiral succinimides.

Combination of fMRI and deep brain stimulation (DBS) allows for large-scale mapping of brain responses to DBS. Here the authors develop highly MRI compatible graphene fiber electrodes for full brain activation pattern mapping under DBS in Parkinsonian rats.

Abstract The utilization of mixed cations is beneficial for taking the advantages of cations and achieving highly efficient perovskite solar cells (PSCs). Herein, the precisely small incorporation of CH(NH2)2 (FA) cations in methyl ammonium lead iodide (MAPbI3) enables the formation of compact, smooth perovskite film with high crystallinity. Consequently, the short-circuit current and the fill factor of the PSCs based on FA x MA1-x PbI3 perovskite are greatly improved, leading to the enhanced device efficiency. The champion PSC based on FA0.1MA0.9PbI3 exhibits a remarkably high efficiency of 22.02%. Furthermore, the PSCs based on FA0.1MA0.9PbI3 perovskite also show improved device stability. This work provides a simple approach to fabricate high-quality perovskite films and high-performance PSCs with better stability.

Leukemia is considered as a multistep progression by progressively genetic modifications that make the conversion of normal human hematopoietic progenitor/stem cells into leukemic cells. In this current investigation, we optimized the reaction of parameters to control the nanoparticle size that was examined via SEM. A various characterization techniques, for example UV–visible spectroscopy, FTIR and EDX were carried out for the synthesized ZnONPs from Rhizoma paridis saponins plant extract. The RPS-ZnONPs were evaluated to inspect their cytotoxic activity against Molt-4 cells via MTT test. Apoptosis was determined through the ROS, MMP and AO/EtBr fluorescent staining techniques. Moreover, pro and anti-apoptotic signaling protein expression was inspected through RT-PCR method. We observed the fabricated RPS-ZnONPs have a crystalline nature, spherical formand various biomolecules were exist. As well, we detected the cytotoxicity effect of synthesized RPS-ZnONPs at a range of 23.5 μg followed to 24hrs treatment. Apoptosis was triggered via the RPS-ZnONPs along with augmented ROS, decreased MMP and altered dual staining. Moreover, the apoptosis were identified through significant up-regulation of Bax, caspase-9 and caspase-3, but the anti-apoptotic protein expression i.e., Bcl-2 was down regulated. Though, this study, we investigated the synthesis, characterization and anticancer activity of ZnONPs of Rhizoma paridis saponins plant extract (RPS-ZnONPs) were useful for treatments of leukemia. Keywords: Zinc oxide nanoparticle, Rhizoma paridis saponins, Apoptosis, Leukemia, Molt-4 cell lines

The unified power flow controller (UPFC) is recognized as one of the most promising flexible ac transmission system (FACTS) devices for modern power systems, due to its versatile functionalities. Based on typical operation conditions, this paper investigates the global and local power flow operation rules of the UPFC embedded transmission system theoretically. First, the detailed global power flow model (GPFM) and the local power flow model (LPFM) are established concerning several selected critical points (SCPs) in the system. The theoretical power flow operation rules for the ranges, the movements and the trajectories of GPFM and LPFM are analyzed, respectively. Then, the case study is performed based on the proposed simplified model, and the results are analyzed from GPFM and LPFM perspectives respectively. The operation rules and the power flow ranges is studied. Further case studies based on the proposed original mathematical model are also carried out, and the results are listed from different viewpoints of two-dimensional planes and three-dimensional spaces. All types of results are also analyzed from GPFM and LPFM perspectives, which verify that the UPFC is adaptive to various operation conditions for power flow regulation.

Modular multilevel converter based high voltage direct current (MMC-HVDC) transmission systems may increase the short-circuit current and affect the AC fault clearing of circuit breakers. To address this issue, this paper analyzes the influence of the MMC on the short-circuit current when a symmetrical or asymmetrical fault occurs in the AC system. Firstly, the influence mechanism of the MMC on the short-circuit current under symmetrical AC faults is studied. It is found that the short-circuit current magnitude at the fault point is mainly affected by the q -axis output current of the MMC. For the single-phase line-ground fault, the three-sequence equivalent circuit of the MMC is analyzed, and the calculation method of the three-sequence short-circuit current is presented. It is observed that the negative- and zero-sequence currents at the valve side of the MMC are both zero, and the positive-sequence current is determined by MMC operating conditions. Besides, the short-circuit current magnitude under the single-phase line-ground fault is also mainly related to the q -axis output current of the MMC. Based on these results, an additional controller is proposed to reduce the short-circuit current under the symmetrical and asymmetrical faults. Finally, the effectiveness of the proposed mechanism and suppression control is verified by PSCAD/EMTDC simulations.

The pole-to-ground fault is one of the most typical faults in modular multilevel converters (MMCs) based DC grid. Analyzing the transient characteristics of fault voltages and currents is of great significance for fault identification, configuration of protection, and optimization of system parameters. This paper proposes an equivalent transient characteristics calculation method for pole-to-ground faults for symmetrical monopolar MMC based DC grid. Firstly, according to the mechanism of the pole-to-ground faults, the fault network and the steady-state network are formed. Then, the star-delta transformation is performed on modelling the MMCs in the fault network, which overcomes the problem that the number of the inserted sub-modules (SMs) in each arm is time-variant. Based on the discrete adjoint model, the pre-fault and faulted matrices describing the voltages and currents are established, and a general method for solving the transient voltages and currents is proposed. Finally, the proposed method is validated in a four-terminal symmetrical monopolar MMC based DC grid. The results show that the proposed method is of high accuracy, and is much more time efficient than time-domain simulation.

Coenzyme Q10 (CoQ10) is an important component of the respiratory chain in humans and some bacteria. As a high-value-added nutraceutical antioxidant, CoQ10 has excellent capacity to prevent cardiovascular disease. The content of CoQ10 in the industrial Rhodobacter sphaeroides HY01 is hundreds of folds higher than normal physiological levels. In this study, we found that overexpression or optimization of the synthetic pathway failed CoQ10 overproduction in the HY01 strain. Moreover, under phosphate- limited conditions (decreased phosphate or in the absence of inorganic phosphate addition), CoQ10 production increased significantly by 12% to220 mg/L, biomass decreased by 12%, and the CoQ10 productivity of unit cells increased by 27%. In subsequent fed-batch fermentation, CoQ10 production reached 272 mg/L in the shake-flask fermentation and 1.95 g/L in a 100-L bioreactor under phosphate limitation. Furthermore, to understand the mechanism associated with CoQ10 overproduction under phosphate- limited conditions, the comparatve transcriptome analysis was performed. These results indicated that phosphate limitation combined with glucose fed-batch fermentation represented an effective strategy for CoQ10 production in the HY01. Phosphate limitation induced a pleiotropic effect on cell metabolism, and that improved CoQ10 biosynthesis efficiency was possibly related to the disturbance of energy metabolism and redox potential. Keywords: R sphaeroides, CoQ10, Phosphate limitation, Overproduction, Scale-up, Transcriptome

Xist is an X-linked ribonucleic acid (RNA) gene responsible for the cis induction of X chromosome inactivation (XCI). In cloned mammalian embryos, Xist is ectopically activated at the morula to blastocyst stage on the X chromosome that is supposed to be active, thus resulting in abnormal XCI. Suppression of erroneous Xist expression by injecting small interfering RNA (siRNA) remarkably increased the developmental efficiency of cloned male mouse embryos by approximately 10-fold. However, injection of anti-Xist siRNA resulted in only a slight increase in the developmental ability of injected cloned male pig embryos because the blocking effect of the injected siRNA was not maintained beyond the morula stage, which is 5 days post-activation. To develop a more effective approach for suppressing the ectopic expression of Xist in cloned pig embryos, we compared the silencing effect of short hairpin RNA (shRNA) and siRNA on Xist expression and the effects of these two Xist knockdown methods on the developmental competence of cloned male pig embryos. Results indicated that an shRNA-based RNA interference (RNAi) has a longer blocking effect on Xist expression than an siRNA-mediated RNAi. Injection of anti-Xist shRNA plasmid into two-cell-stage cloned male pig embryos effectively suppressed Xist expression, rescued XCI at the blastocyst stage, and improved the in vitro developmental ability of injected cloned embryos. These positive effects, however, were not observed in cloned male pig embryos injected with anti-Xist siRNA. This study demonstrates that vector-based rather than siRNA-mediated RNAi of Xist expression can be employed to improve pig cloning efficiency.

The Duroc × (Landrace × Yorkshire) hybrid pigs (DLY) are the most popular commercial pigs, providing consumers with the largest source of pork. In order to gain more insights into the genetic architecture of economically important traits in pigs, we performed a genome-wide association study (GWAS) using the GeneSeek Porcine 50 K SNP Chip to map the genetic markers and genes associated with body conformation traits (BCT) in 311 DLY pigs. The quantitative traits analyzed included body weight (BW), carcass length (CL), body length (BL), body height (BH), and body mass index (BMI). BMI was defined as BMICL, BMIBL, and BMIBH, respectively, based on CL, BL, and BH phenotypic data. We identified 82 SNPs for the seven traits by GEMMA-based and FarmCPU-based GWASs. Both methods detected two quantitative trait loci (QTL) on SSC8 and SSC17 for body conformation traits. Several candidate genes (such as TNFAIP3, KDM4C, HSPG2, BMP2, PLCB4, and GRM5) were found to be associated with body weight and body conformation traits in pigs. Notably, the BMP2 gene had pleiotropic effects on CL, BL, BH, BMICL, and BMIBL and is proposed as a strong candidate gene for body size due to its involvement in growth and bone development. Furthermore, gene set enrichment analysis indicated that most of the pathway terms are associated with regulation of cell growth, negative regulation of cell population proliferation, and chondrocyte differentiation. We anticipate that these results further advance our understanding of the genetic architecture of body conformation traits in the popular commercial DLY pigs and provide new insights into the genetic architecture of BMI in pigs.

BackgroundPrevious studies indicated the calcium-binding protein S100A12 to be involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of S100A12 has remained elusive in patients with community-acquired pneumonia (CAP). Therefore, the purpose of this prospective cohort study was to evaluate the association between serum S100A12 with severity and prognosis in CAP patients.MethodsTwo groups with either 239 CAP patients or 239 healthy controls were enrolled in our study. Fasting blood and clinical characteristics were collected. On admission, serum S100A12 was measured using enzyme-linked immunosorbent assay (ELISA).ResultsSerum S100A12 was increased in CAP patients compared to control subjects. Furthermore, serum S100A12 was elevated according to the severity of CAP. Correlative analysis suggested that the level of serum S100A12 was associated with blood routine indices, renal function markers, inflammatory cytokines and other clinical parameters among CAP patients. Additionally, linear and logistical regression analyses indicated that serum S100A12 was positively associated with CAP severity scores in CAP patients. In addition, the association of high serum S100A12 and prognosis was accessed using a follow-up research. Elevated serum S100A12 on admission increased the risk of death and hospital stay in CAP patients during hospitalization.ConclusionsElevated serum S100A12 on admission is positively associated with the severity and adverse prognosis in CAP patients, suggesting that S100A12 may involve in the pathophysiological process of CAP. The titre of serum S100A12 may be used as a biomarker for diagnosis and prognosis among CAP patients.

The same doses of anesthesia may yield varying depths of anesthesia in different patients. Clinical studies have revealed a possible causal relationship between deep anesthesia and negative short- and long-term patient outcomes. However, a reliable index and method of the clinical monitoring of deep anesthesia and detecting latency remain lacking. As burst-suppression is a characteristic phenomenon of deep anesthesia, the present study investigated the relationship between burst-suppression latency (BSL) and the subsequent burst-suppression ratio (BSR) to find an improved detection for the onset of intraoperative deep anesthesia. The mice were divided young, adult and old group treated with 1.0% or 1.5% isoflurane anesthesia alone for 2 h. In addition, the adult mice were pretreated with intraperitoneal injection of ketamine, dexmedetomidine, midazolam or propofol before they were anesthetized by 1.0% isoflurane for 2 h. Continuous frontal, parietal and occipital electroencephalogram (EEG) were acquired during anesthesia. The time from the onset of anesthesia to the first occurrence of burst-suppression was defined as BSL, while BSR was calculated as percentage of burst-suppression time that was spent in suppression periods. Under 1.0% isoflurane anesthesia, we found a negative correlation between BSL and BSR for EEG recordings obtained from the parietal lobes of young mice, from the parietal and occipital lobes of adult mice, and the occipital lobes of old mice. Under 1.5% isoflurane anesthesia, only the BSL calculated from EEG data obtained from the occipital lobe was negatively correlated with BSR in all mice. Furthermore, in adult mice receiving 1.0% isoflurane anesthesia, the co-administration of ketamine and midazolam, but not dexmedetomidine and propofol, significantly decreased BSL and increased BSR. Together, these data suggest that BSL can detect burst-suppression and predict the subsequent BSR under isoflurane anesthesia used alone or in combination with anesthetics or adjuvant drugs. Furthermore, the consistent negative correlation between BSL and BSR calculated from occipital EEG recordings recommends it as the optimal position for monitoring burst-suppression.

Helicobacter pylori exhibit specific geographic distributions that are related to clinical outcomes. Despite the high infection rate of H. pylori throughout the world, the genetic epidemiology surveillance of H. pylori still needs to be improved. This study used the single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) to facilitate genomic population analyses of H. pylori and encourage the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 public H. pylori genomes were downloaded and used to construct the typing tool, named HpTT (H. pylori Typing Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent-scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolate source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main sources of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their dataset against the existing global database easily and rapidly, a user-friendly website (https://db.cngb.org/HPTT/) was developed with both genomic typing tools and visualization tools. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary, the H. pylori typing tool (HpTT) is a novel genomic epidemiological tool that can achieve high-resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure, evolution analysis, and epidemiological surveillance of H. pylori.

Farm animal salivary glands hold great potential as efficient bioreactors for production of human therapeutic proteins. Nerve growth factor (NGF) is naturally expressed in animal salivary glands and has been approved for human clinical treatment. This study aims to employ transgenic (TG) pig salivary gland as bioreactors for efficient synthesis of human NGF (hNGF). hNGF-TG pigs were generated by cloning in combination with piggyBac transposon-mediated gene transfer. These hNGF-TG pigs specifically expressed hNGF protein in their salivary glands and secreted it at high levels into saliva. Surgical and nonsurgical approaches were developed to efficiently collect saliva from hNGF-TG pigs. hNGF protein was successfully purified from collected saliva and was verified to be biologically active. In an additional step, the double-transgenic pigs, where the endogenous porcine NGF (pNGF) gene was replaced by another copy of hNGF transgene, were created by cloning combined with CRISPR/Cas9-mediated homologous recombination. These double-transgenic pigs expressed hNGF but not pNGF, thus avoiding possible “contamination” of hNGF with pNGF protein during purification. In conclusion, TG pig salivary glands can be used as robust bioreactors for a large-scale synthesis of functional hNGF or other valuable proteins. This new animal pharming method will benefit both human health and biomedicine.

This paper reports a method to generate tunable bottle beams using an ultrasonic lens, by which the bottle position can be precisely adjusted with the change of the acoustic frequency. Therefore, the position of a single particle or bubble in liquid can be manipulated without using phased array which is costly and huge with complex circuits. Furthermore, we introduced this method to multiple bubble manipulation using acoustic holography. The bottle properties against frequency are theoretically and experimentally analyzed. It is shown that the bottle position depends almost linearly on the operating frequency, which provides a basis for the precise manipulation of bubbles and particles. In addition, the relationship between the acoustic radiation force and the drag force under different incident acoustic pressures is considered, establishing a limit on the moving velocity of the trapped particles. The ultrasonic field observation is further demonstrated by Schlieren imaging system. The proposed method has potential biomedical applications, such as more flexible cell manipulation and targeted drug delivery in vivo, as well as potential applications in the study of chemical reactions between micro objects.

Understanding picophytoplankton variations that play important roles in the material circulation and energy flow are critical to assessing overall status of waterbody, especially for clean reservoirs which remain a relatively stable community structure and high species diversity due to lower nitrogen and phosphorus nutrients. However, their response to key environmental factors and tightly acting microbial remains poorly understood. Traditional quantification methods are limited, such as chlorophyll-a, turbidity and microscope. There are still many defects with present molecular analysis. In this study, a flow cytometric analysis and high-throughput sequencing combination methodology was developed and tested on clean water from a reservoir, by a monthly dynamic for a vegetative period April-September in 2019 to improve the accuracy of dynamic monitoring for the picophytoplankton system. More species of Pico-Cyanobacteria and Pico-Eukaryotes were discovered. The increased percentage of pigment compounds from 8.2% to 76.3% proves the effective reduce of heterotrophic disturbing and enrichment of target populations. Picophytoplankton that was previously neglected due to their low relative abundance has once again entered the scope of our eyes. Phytoplankton were divided into three categories. The first one was the highly abundant and frequently present taxa, the second one was the low-abundance but highly-transient population, and the third one was the low abundance and stable group. Synechococcus, Emiliania, Tetraselmis and Thalassiosira were dominant picophytoplankton and displayed obvious temporal and spatial distribution characteristics. Pico-PE rich Cyanobacteria and Nano-Eukaryotes with high transience abnormally increased in summer. Temperature, ammonia-N, nitrate-N, turbidity and total nitrogen were most influencing factors, while some picophytoplankton with special physiological structure showed distinct competitive advantages in the microbial community. As for the off-flavor compounds, the concentration of 2-methylisoborneol and geosmin were high even 66.7% and 20.8% of the samples exceeded their olfactory threshold. Chrysochromuina, Planktothrix and Microcystis might be the potential producers.