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As a novel third-generation EGFR tyrosine kinase inhibitor (TKI), SH-1028 (formerly oritinib) is developed to inhibit both sensitizing EGFR mutations and EGFR T790M mutation.This was a multicenter, single-arm, open-label, phase 2 trial (NCT03823807). Eligible patients were those with advanced NSCLC with centrally confirmed EGFR T790M mutation who progressed after first- or second-generation EGFR TKIs or with primary EGFR T790M mutations. Each patient received SH-1028 tablets orally at 200 mg/d until disease progression or intolerable toxicity. Tumor response was evaluated every 6 weeks per the Response Evaluation Criteria in Solid Tumors, version 1.1. The primary end point was objective response rate by an independent review committee. The secondary end points were progression-free survival, overall survival (OS), disease control rate, safety, and so on.A total of 286 patients with EGFR T790M-positive advanced NSCLC were enrolled in this study, including 59 patients in part A (dose-verification study) and 227 patients in part B (second-line registration study). By data cutoff on September 17, 2021, the independent review committee-assessed objective response rate was 55.9% (95% confidence interval [CI]: 42.4-68.8) in part A and 60.4% (95% CI: 53.7-66.8) in part B. The median progression-free survival was 12.4 months (95% CI: 8.3-20.8) in part A and 12.6 months (95% CI: 9.7-15.3) in part B. The median OS was 26.0 months (95% CI: 23.3-not reached) in part A, and OS was immature in part B. Among the 286 patients, 44 of them experienced at least one grade 3 or higher treatment-related adverse event, with the most common ones as increased serum creatinine phosphokinase level (13 [4.5%]), diarrhea (six [2.1%]), and prolonged QT interval (three [1.0%]). Treatment-related skin rash was reported in 26 patients (9.1%), all grade 1 or 2. There was no interstitial lung disease reported in this study.SH-1028 is efficacious and tolerable in second-line treatment of patients with advanced NSCLC with positive EGFR T790M.

High-dose influenza vaccine offers better protection against influenza/associated complications compared with standard-dose formulation. We evaluated immunogenicity and safety of high-dose influenza vaccine (QIV-HD) and standard-dose (QIV-SD) in older adults (≥ 65 years) in Taiwan.This was a phase III, randomized, modified double-blind, active-controlled, multi-center, descriptive study in older adults. Participants (N = 165) were randomized 1:1 to receive QIV-HD or QIV-SD vaccine (clinicaltrials.gov#NCT04537234).For all four influenza strains, geometric means titers (GMTs) of hemagglutination inhibition were higher for the QIV-HD than QIV-SD with adjusted GMT ratios (95 % CI) of 2.65 (1.87-3.75) for A/H1N1; 1.76 (1.31-2.38) for A/H3N2; 2.60 (1.90-3.56) for B/Victoria; and 2.01 (1.57-2.56) for B/Yamagata. The seroconversion was higher for QIV-HD than QIV-SD with similar safety profiles across both groups.QIV-HD was highly immunogenic for four influenza strains and have acceptable safety profile in older adults aged ≥ 65 years in Taiwan.

Ridge-furrow rainwater harvesting (RFRH) is known to be effective in controlling water loss and soil erosion, and increasing soil moisture and crop yield in semiarid regions. However, it can cause waterlogging, ridge overtopping, and harvest failure if not properly designed. A four consecutive-year field trial was carried out to assess the impacts of various slope gradients and tillage practices on soil moisture, runoff, sediment yield, associated soil nutrient losses, fodder yield, and water use efficiency (WUE) of alfalfa in the Loess Plateau, China. The trial adopted a split-plot design, taking slope gradient (5° and 10°) as main plot treatment and tillage practice (traditional tillage, open-ridging, and tied-ridging) as split-plot treatment, from 2015 to 2018. There were greater variations in runoff, sediment yield, and associated soil nutrient losses than in fodder yield and WUE. Tied-ridging and open-ridging resulted in decreased runoff and reduced sediment transport and associated soil nutrient losses, and increased soil moisture, fodder yield, and WUE. Runoff, sediment transport, and associated soil nutrient losses inclined with increasing slope; while fodder yield and the WUE declined. For slopes of 5° and 10°, the average decrease in runoff, sediment yield, total nitrogen, total phosphorus, and organic matter losses for open-ridging were 47.7–56.2%, 91.0–92.7%, 90.4–93.1%, 90.1–92.2%, and 88.9–90.2%, respectively, while these for tied-ridging were 62.4–68.4%, 94.5–96.4%, 93.6–95.5%, 93.9–95.9%, and 93.0–94.9%, over 4 years as compared with traditional tillage. The mean annual runoff, sediment, total nitrogen, total phosphorus, and organic matter losses for slopes of 10° were 1.31, 1.96, 1.87, 1.99, and 1.64 times greater than the corresponding values for slopes of 5°, respectively. The increase of fodder yield and WUE for open-ridging and tied-ridging was 40.1–45.6% and 16.0–17.5%, and 3.66–5.99 and 1.35–2.50 kg ha−1 mm−1, respectively, for slopes of 5° and 10°. The average fodder yield and WUE for slopes of 5° were 1.19 and 1.23 times greater than corresponding values for slopes of 10°, respectively. The disparities in fodder yield and WUE of alfalfa between slopes of 5° and 10° were not clear in dry years, but were evident in wet years. Tied-ridging was recommended for water and soil conservation, while open-ridging was recommended for increase of fodder yield and WUE of alfalfa. The implementation of RFRH in crop production should be evaluated by the use of a model in accordance with climatic conditions, soil type, and plant species.

Cyclophilin D (CypD) can stimulate the opening of the membrane permeability transition pore (mPTP) and regulate mitochondrial function. Whole-body knockout of CypD improved high fat diet-induced hepatic steatosis by reducing the excess opening of the mPTP and lipid deposition. However, whether CypD significantly ameliorates nonalcoholic steatohepatitis (NASH) has not been studied. Therefore, we established liver-specific CypD knockout (CypD LKO) mice and fed a HFHC diet to induce NASH. Compared with the wild-type mice, the CypD LKO not only showed improved lipid deposition and insulin resistance by increasing fatty acid oxidation but also displayed ameliorated hepatic inflammation, although the symptoms of fibrosis in the NASH model were not significantly improved. In addition, we used bile duct ligation (BDL) or a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to induce cholestatic disease and found that CypD LKO had also no significant effect on acute fibrosis. Thus, CypD LKO can inhibit the progression of early NASH by ameliorating steatosis and inflammatory symptoms. These results suggest a new strategy for the treatment of early NASH.

The endoderm, one of the three primary germ layers, gives rise to lung, liver, stomach, intestine, colon, pancreas, bladder, and thyroid. These endoderm-originated organs are subject to many life-threatening diseases. However, primary cells/tissues from endodermal organs are often difficult to grow in vitro. Human pluripotent stem cells (hPSCs), therefore, hold great promise for generating endodermal cells and their derivatives for the development of new therapeutics against these human diseases. Although a wealth of research has provided crucial information on the mechanisms underlying endoderm differentiation from hPSCs, increasing evidence has shown that metabolism, in connection with epigenetics, actively regulates endoderm differentiation in addition to the conventional endoderm inducing signals. Here we review recent advances in metabolic and epigenetic regulation of endoderm differentiation.

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been found to be the culprit in the coronavirus disease (COVID-19), causing a global pandemic. Despite the existence of many vaccine programs, the number of confirmed cases and fatalities due to COVID-19 is still increasing. Furthermore, a number of variants have been reported. Because of the absence of approved anti-coronavirus drugs, the treatment and management of COVID-19 has become a global challenge. Under these circumstances, drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials. Here, we summarize the current status of the application of drug repurposing in COVID-19, including drug repurposing based on virtual computer screening, network pharmacology, and bioactivity, which may be beneficial COVID-19 treatment., Graphical abstract Image 1

Background Parathyroid hormone (PTH) and vitamin D plays a major role in calcium (Ca) homeostasis and bone turnover . The purpose of this study was to assess which factors (sex, age, time of blood sampling, season of the year, temperature and sunshine hours (SHH)) had the greatest impact on plasma PTH, 25-OH-VitD, and Ca levels, and then whether these effects were clinically acceptable in a large number of Southwestern Chinese subjects. Method The data was from West China Hospital Health Examination Center, Sichuan University from April 1, 2018 to June 30, 2019. A total of 18,664 physical examination subjects were included. PTH and 25-OH-VitD were measured by a Roche Cobas e 601, and Ca was measured by a Roche Cobas 8000. Linear regression models were used to assess correlations between PTH, 25-OH-VitD, Ca and the above factors. Results The concentrations of serum PTH in females were significantly higher than those in males, while the 25-OH-VitD and Ca were opposite. The concentration of PTH in data collection decreased in summer and increased in spring. The concentration of 25-OH-VitD decreases in spring and increases in autumn. PTH concentrations were negatively correlated with last month temperature and SHH, while 25-OH-VitD were opposite. Linear regression showed that season may be the main factor affecting serum PTH and 25-OH-VitD levels, and these effects were not clinically acceptable. Conclusion In order to avoid influencing clinicians' investigation of suspected hyperparathyroidism and hypovitaminosis, reference intervals for PTH, 25-OH-VitD, and Ca should be established, taking into account sex, age and the season.

Submergence tolerance is crucial when thinking in promising species for restoration of ecosystems prone to suffer extreme flooding events. In this study, two-year-old seedlings of Distylium chinense were subjected to one field study and five controlled experiments: unsubmerged and watered daily as controls (CK) and completely submerged for 30, 60, 90 and 120 days, respectively followed by a 60-day recovery period to test the submergence tolerance. The results showed that the survival decreased with the increasing flooding duration. Different submergence duration treatments affected dry mass accumulation and carbohydrate content of roots, stems and leaves. Flooding stress affected the activities of pyruvate decarboxylase (PDC), ethanol dehydrogenase (ADH) and lactic dehydrogenase (LDH) enzymes, which indicated the roots and leaves adapt to long-term flooding by reinforcing their anaerobic respiration and activities of ADH were higher than those of LDH for roots and leaves with stronger alcoholic fermentation mainly. After de-submergence, the recovery patterns of carbohydrate were coincided with those of dry mass accumulation of the roots, stems and leaves. A significant regression equation analysis showed root starch content and dry mass accumulation were the major factors affecting the seedling survival. And D. chinense accumulated substantial amounts of carbohydrate before submergence and invested more in roots and stems than in leaves, which enhances long-term survival under submergence. Carbohydrate storage is a key functional trait that can explain high survival under submergence. D. chinense may have adopted a suite of growth and respiratory metabolic adaptation strategies to survive long-term submergence.

5-Methylcytosine (m5C) is a well-known post-transcriptional modification that plays significant roles in biological processes, such as RNA metabolism, tRNA recognition, and stress responses. Traditional high-throughput techniques on identification of m5C sites are usually time consuming and expensive. In addition, the number of RNA sequences shows explosive growth in the post-genomic era. Thus, machine-learning-based methods are urgently requested to quickly predict RNA m5C modifications with high accuracy. Here, we propose a noval support-vector-machine (SVM)-based tool, called iRNA-m5C_SVM, by combining multiple sequence features to identify m5C sites in Arabidopsis thaliana. Eight kinds of popular feature-extraction methods were first investigated systematically. Then, four well-performing features were incorporated to construct a comprehensive model, including position-specific propensity (PSP) (PSNP, PSDP, and PSTP, associated with frequencies of nucleotides, dinucleotides, and trinucleotides, respectively), nucleotide composition (nucleic acid, di-nucleotide, and tri-nucleotide compositions; NAC, DNC, and TNC, respectively), electron-ion interaction pseudopotentials of trinucleotide (PseEIIPs), and general parallel correlation pseudo-dinucleotide composition (PC-PseDNC-general). Evaluated accuracies over 10-fold cross-validation and independent tests achieved 73.06% and 80.15%, respectively, which showed the best predictive performances in A. thaliana among existing models. It is believed that the proposed model in this work can be a promising alternative for further research on m5C modification sites in plant., Graphical Abstract, 5-Methylcytosine (m5C) is a well-known post-transcriptional modification, which plays a significant role in various biological processes. Dou et al. built a novel SVM-based predictor, called iRNA-m5C_SVM, to identify RNA m5C modifications using multiple sequence features. Corresponding performances were performed with other reported methods, which provided a competitive bioinformatic tool to predict m5C sites.

Japanese encephalitis virus (JEV) is an infectious pathogen spreading in a wide range of vertebrate species. Pigs are amplifying hosts of JEV and thought to be maintained in nature predominantly by avian-mosquito cycles. In the innate immune system, interferon-inducible transmembrane protein (IFITM) is a small transmembrane protein family and has been identified as the first line of defense against a broad range of RNA virus invasion. In this paper, we found that swine IFITM (sIFITM) could restrict the replication of both JEV vaccine strain and wild strain NJ-2008. The cysteine S-palmitoylation modification of sIFITM plays important roles in their anti-JEV effects and intracellular distributions. Our findings show the anti-JEV activities of swine interferon-inducible transmembrane proteins and broaden the antiviral spectrum of IFITM protein family. The preliminary exploration of S-palmitoylation modification of sIFITM may contribute to understanding of the antiviral molecular mechanism of sIFITM.

Changes in solution chemistry and transport conditions can lead to the release of deposited MnO2 nanoparticles from a solid interface, allowing them to re-enter the aqueous environment. Understanding the release behavior of MnO2 nanoparticles from naturally occurring surfaces is critical for better prediction of the transport potential and environmental fate of MnO2 nanoparticles. In this study, the release of MnO2 nanoparticles was investigated using a quartz crystal microbalance with dissipation monitoring (QCM-D), and different environmental surface types, solution pH values and representative macromolecular organics were considered. MnO2 nanoparticles were first deposited on crystal sensors at elevated NaNO3 concentrations before being rinsed with double-deionized water to induce their remobilization. The results reveal that the release rate of MnO2 depends on the surface type, in the decreasing order: SiO2 > Fe3O4 > Al2O3, resulting from electrostatic interactions between the surface and particles. Moreover, differences in solution pH can lead to variance in the release behavior of MnO2 nanoparticles. The release rate from surfaces was significantly higher at pH 9.8 that at 4.5, indicating that alkaline conditions were more favorable for the mobilization of MnO2 in the aquatic environment. In the presence of macromolecular organics, bovine serum albumin (BSA) can inhibit the release of MnO2 from the surfaces due to attractive forces. In presence of humic acid (HA) and sodium alginate (SA), the MnO2 nanoparticles were more likely to be mobile, which may be associated with a large repulsive barrier imparted by steric effects.

The effectiveness of contracts in terms of cooperative efficiency and relational outcomes in interorganizational relationships has become critical in today's volatile markets. However, extant research on the effect of contracts on trust has found inconsistent results, possibility because of its overwhelming focus on an economic fitness perspective at the expense of a social fitness perspective. Drawing insights from institutional theory, we focus on legitimacy building in interfirm contract design, investigate how contract legitimacies (i.e., regulative, normative, and cognitive) influence the effectiveness of interfirm contract design, and further explore the moderating effects of influence strategies that are applied in the process of contract implementation. Using longitudinal field survey data and archival data, this study finds that the three types of contract legitimacy play different roles in influencing compliance and trust and that noncoercive influence strategies can improve the effectiveness of regulative and normative legitimacy better than coercive influence strategies on trust. The findings offer new theoretical and managerial insights into the role of institutional environments in the effectiveness of contract design in manufacturer–distributor relationships.

Microglia-mediated neuroinflammation plays an important role in multiple sclerosis (MS). This study explored whether curcumin has a protective effect on experimental autoimmune encephalomyelitis (EAE), and the specific mechanism was investigated. We found that curcumin attenuates the severity of EAE mice. It inhibits the activation of microglia in the spinal cord of EAE mice and LPS-stimulated BV-2 cells. The findings clarify that curcumin may inhibit the inflammatory response mediated by microglia by inactivating the AXL/JAK2/STAT3 signaling pathway, which laid a theoretical foundation for the clinical management of MS.

Using first-principles calculation, we have studied the adsorption effect of small gas molecules (H2O, CO2, CH4, SO2, H2S, and NH3) on GeP3 monolayer. To determine the most stable adsorption site, five adsorption sites (center, Ge, P, bridge Ge P, and bridge P P) were considered in the paper. Through calculations of adsorption energy, adsorption distance, and charge transfer, we preliminarily determined that H2O, CO2, and CH4 were physically adsorbed on GeP3 via weak van der Waals force. However, SO2, H2S, and NH3 were chemically adsorbed on GeP3 with new covalent bonds formed, as concluded by calculations of electron localization function and charge density difference. Gas molecule adsorption can cause significant changes in the band gap of single-layer GeP3, indicating that pristine GeP3 monolayer is sensitive to these gases. In addition, the adsorption energy of the H2O, CO2, and CH4 adsorbed on GeP3 can be tuned effectively by employing an external electric field. Our theoretical studies reveal that GeP3 monolayer is a promising gas-sensitive material used in nanometer devices.

Yin Yang 1 (YY1) is a zinc-finger protein that plays critical roles in various biological processes by interacting with DNA and numerous protein partners. YY1 has been reported to play dual biological functions as either an oncogene or tumor suppressor in the development and progression of multiple cancers, but its role in human nasopharyngeal carcinoma (NPC) has not yet been revealed. In this study, we found that YY1 overexpression significantly inhibits cell proliferation and cell-cycle progression from G1 to S and promotes apoptosis in NPC cells. Moreover, we identified YY1 as a component of the c-Myc complex and observed that ectopic expression of YY1 inhibits c-Myc transcriptional activity, as well as the promoter activity and expression of the c-Myc target gene microRNA-141 (miR-141). Furthermore, restoring miR-141 expression could at least partially reverse the inhibitory effect of YY1 on cell proliferation and tumor growth and on the expression of some critical c-Myc targets, such as PTEN/AKT pathway components both in vitro and in vivo. We also found that YY1 expression is reduced in NPC tissues, negatively correlates with miR-141 expression and clinical stages in NPC patients, and positively correlates with survival prognosis. Our results reveal a previously unappreciated mechanism in which the YY1/c-Myc/miR-141 axis plays a critical role in NPC progression and may provide some potential and valuable targets for the diagnosis and treatment of NPC.

In the past decades, the microbial fuel cell (MFC) technology has caught the attention of the scientific community for its potential in transforming petroleum hydrocarbon (PHC) pollutants directly into electricity through microbial catalyzed anodic. The microbe was one of the most important factors that both influence MFCs and PHC degradation. Here we aimed to identify new microbes to expand the list of microbial species which are both electrogenic and diesel hydrocarbon degrading. In this text, we depicted a strain of microbe named E2, isolated from on the anode surface of MFC, and using diesel as sole carbon source. E2 exhibited electrochemical activity in cyclic voltammetry curve, implicating that it had electrogenic ability. E2 degraded about 50% diesel (3.26 g/L) in maximum during 8 days. Pyrosequencing of 16S rRNA gene of E2 revealed E2 was a sub-strain of Vibrio. Corresponding to salt and alkali tolerant properties of vibrio, the optimal condition for E2 in degrading diesel was 3%–4% in salinity, and pH 8–9 in mineral medium. Collectively, as a member of Gammaproteobacteria class, E2 was novel marine microbe both electricity generation and diesel degradation, which may attract its future application toward artificial microbial community construction in MFC in promoting the PHC pollution removal.

Over the past decade or so, the deadlock control problem of automated manufacturing systems (AMSs) with unreliable resources received a great deal of research attention. Most existing work to date assumes that the studied AMSs contain a single unreliable resource. Most existing control methods belong to the class of deadlock avoidance ones. This paper focuses on deadlock prevention for AMS with multiple unreliable resources. Our goal is to guarantee the continuous production of those parts not requiring any of the failed resources in case of any resource failure. A Petri net model is developed to characterize the failure and repair of unreliable resources. Based on it, a robust deadlock prevention controller that satisfies the above desired property is proposed. Experimental results indicate its effectiveness and superiority over the state-of-the-art methods.

Sensorimotor functional recovery after spinal cord injury (SCI) is still a large challenge in the clinic. Cabazitaxel (Cab) is a microtubule inhibitor approved by the FDA in 2010 for metastatic castration-resistant prostate cancer. Interestingly, we had detected that Cab promoted neurite outgrowth of the cultured cortical neurons. To further study whether Cab facilitates locomotion repair and figure out the underlying mechanism, we designed an injectable and biodegradable hybrid hydrogel (Cab-M/H) to improve the solubility and bioavailability of Cab, and the rat lateral hemisection model was established. After local application, Cab-M/H formed a 3D cross-linked hydrogel, which served as a drug reservoir, and the hydrogel matrix degraded gradually with the sustained release of Cab. BBB scoring and electrophysiology test indicated that Cab-M/H effectively promoted motor behavioral recovery. Pathological assay suggested Cab-M/H significantly reduced fibrotic scarring and decreased deposition of the axon-growth inhibitory molecules, as well boosted nerve regeneration and prevented demyelination around the injury site. Furthermore, the Cab-M/H treatment did not initiate any relative abnormal pathologic changes. These data demonstrate that a single low-dose administration of Cab-M/H at the injury site potently facilitates functional recovery. Therefore, the study provides a new and promising candidate for the global fight against SCI.

Tannic acid, a hydrolysable tannin, exists commonly in food plants. Tannic acid has already been shown various anticancer mechanisms such as inhibiting the proliferation, inducing a higher apoptotic rate and slowing down the metastasis of different cancers. Moreover, tannic acid was reported to reduce the side effects caused by chemotherapeutics on patients. But whether the tannic acid can improve the treatment of oxaliplatin on colorectal carcinomatosis has yet been studied. In this study, we developed an injectable drug delivery system by physical incorporation of oxaliplatin (OXA) and tannic acid (TA) polymeric nanoparticles (OXA/TA NPs) into a thermo-sensitive hydrogel, OXA/TA NPs-hydrogel (OXA/TA NPs-H). The OXA/TA NPs-H was injected into the peritoneal cavity for the treatment of colorectal peritoneal carcinoma. Firstly, a water-in-oil-in-water double-emulsion (w/o/w) method and solvent-evaporation procedure were used in the preparation of the biodegradable OXA/TA NPs. Then, we prepared the biodegradable thermo-sensitive poly(3-caprolactone) (PCL)-10R5-PCL (PCLR) hydrogel with a low critical solution temperature (LCST) which undergoes gelation process at body temperature. Transmission electron microscopy (TEM) showed the spherical profile of OXA/TA NPs. Fourier-transform infrared (FTIR) spectra demonstrated that OXA and TA were both encapsulated into the OXA/TA NPs. In this study, intraperitoneal application of OXA/TA NPs-H restricted the growth of CT26 peritoneal colon cancer in vivo, improved the quality of life and prolonged the survival time of the model mice. Our study suggested that OXA/TA NPs-H might have potential application in the treatment of colorectal cancer.

Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck squamous carcinoma that is notorious for its high metastatic potential. In this study, we reported that FOXA1 protein was decreased in NPC cells. Loss of FOXA1 is associated with lymph node metastasis and poor prognosis. Silencing FOXA1 in NP69 and C666-1 NPC cells accelerated cell proliferation and migration, while re-expression of FOXA1 has opposite effects. Microarray and RNA-seq analysis revealed that re-expression of FOXA1 in NPC cells reprogrammed the TGF-β-stimulated transcription program, which is characterized by promotion of TGF-β-inducible tumor-suppressive targets but repression of TGF-β-inducible oncogenes expression in NPC cells, leading to restoration of NPC cell sensitivity to TGF-β's growth-inhibitory effect. BAMBI, a TGF-β responsive tumor suppressor, was induced by FOXA1 in NPC cells. FOXA1 binding on the BAMBI gene facilitated SMAD2/3 binding to the BAMBI promoter via increasing BAMBI associated H3K4me1 and H3K27ac modification. Enforced expression of BAMBI in NPC cells suppressed cell proliferation and invasiveness. Our data suggested that FOXA1 is a master factor in controlling the TGF-β-stimulated transcriptome and a regulator of TGF-β biological functions in NPC oncogenesis.

Bronchopulmonary dysplasia is a common respiratory disease in premature infants. The severity is diagnosed at the 56th day after birth or discharge by analyzing the clinical indicators, which may cause the delay of the best treatment opportunity. Thus, we proposed a deep learning-based method using chest X-ray images of the 28th day of oxygen inhalation for the early severity prediction of bronchopulmonary dysplasia in clinic.We first adopted a two-step lung field extraction method by combining digital image processing and human-computer interaction to form the one-to-one corresponding image and label. The designed XSEG-Net model was then trained for segmenting the chest X-ray images, with the results being used for the analysis of heart development and clinical severity. Therein, Six-Point cardiothoracic ratio measurement algorithm based on corner detection was designed for the analysis of heart development; and the transfer learning of deep convolutional neural network models were used for the early prediction of clinical severities.The dice and cross-entropy loss value of the training of XSEG-Net network reached 0.9794 and 0.0146. The dice, volumetric overlap error, relative volume difference, precision, and recall were used to evaluate the trained model in testing set with the result being 98.43 ± 0.39%, 0.49 ± 0.35%, 0.49 ± 0.35%, 98.67 ± 0.40%, and 98.20 ± 0.47%, respectively. The errors between the Six-Point cardiothoracic ratio measurement method and the gold standard were 0.0122 ± 0.0084. The deep convolutional neural network model based on VGGNet had the promising prediction performance, with the accuracy, precision, sensitivity, specificity, and F1 score reaching 95.58 ± 0.48%, 95.61 ± 0.55%, 95.67 ± 0.44%, 96.98 ± 0.42%, and 95.61±0.48%, respectively.These experimental results of the proposed methods in lung field segmentation, cardiothoracic ratio measurement and clinic severity prediction were better than previous methods, which proved that this method had great potential for clinical application.

Background: Early pregnancy loss is the most common complication in pregnancy. Recently, semen has been identified as regulator of female reproductive function. Here, we investigate latent promising seminal exosomal miRNA as a clinically applicable bio-regulator that can promote the biological function of trophoblast cells in early pregnancy. Objective: To study the regulation and mechanism of semen on embryonic trophoblasts. Methods: Compare the expression of Notch1 in fetal villi of in vitro fertilization-embryo transfer (IVF-ET)-conceived and intercourse-conceived by immunohistochemical staining. Seminal exosome (SE) and miR-181a-5p highly expressed in SE were co-cultured with trophoblast cell line HTR-8/Svneo cells to detect the effect and mechanism of SE and miR-181a-5p on the biological functions of trophoblasts. Results: The expression of Notch1 in the villi tissue from IVF (in vitro fertilization)-conceived women was significantly decreased compared with that from intercourse-conceived women, this may be the reason why IVF pregnancy complications are higher than natural pregnancy. In vitro experiments, we found that both SE and miR-181a-5p significantly increased the migration, invasion and angiogenesis of HTR-8/Svneo cells through inhibiting the expression of PROX1 and then activating Notch1 signaling pathway in HTR-8/Svneo cells. Conclusions: We found that the decreased expression of villous Notch1 may be one of the causes of early pregnancy loss (EPL) in IVF. Semen exosomes can protect the establishment and maintenance of pregnancy by promoting the biological function of trophoblast cells through the miR181-PROX1-Notch1 signaling pathway. Funding: This study was supported by the National Natural Science Foundation of China (CSFC) (grant No. 81471455 and No. 81100418). Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Research Ethics Committee of Renmin Hospital of Wuhan University (No. WDRY2021-K044).

An anti-phenolphthalein monoclonal antibody (mAb) was prepared based on the N' N-carbonyldiimidazole (CDI) method through phenolphthalein conjugated with proteins. Indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and colloidal gold-based immunochromatographic assay (ICA) methods were used to determine phenolphthalein in slimming products. A standard curve was established, and the IC50 and limit of detection of ic-ELISA were 0.95 and 0.10 ng/mL with a linear detection range of 0.27-3.37 ng/mL. The developed ICA was used to detect phenolphthalein in tablets, capsules, and slimming tea samples with visual limit of detection values of 10 ng/mL, and cut-off values of 200 ng/mL. The results indicated that these two methods could be used to quickly detect phenolphthalein in slimming products.

Sleep is vital for most animals, yet its mechanism and function remain unclear. The blood-brain barrier GPCR moody is upregulated in sleep-deficient insomniac (inc) null Drosophila, suggesting a link between the blood-brain barrier (BBB) and sleep. We found that permeability of the BBB–the organ required for maintenance of homeostatic levels of nutrients, ions, and other molecules in the brain–displays circadian clock-dependent rhythmicity that is aligned with sleep/wake cycles. We observed increased BBB permeability in the chronically sleep-deprived sleep mutants insomniac, wakeD1, wakeD2 and sleepless, as well as acutely sleep deprived animals. In addition to tracers, sleep deprivation-induced BBB changes also increased penetration of drugs used in the treatment of brain pathologies. After chronic or acute sleep deprivation, rebound sleep, or administration of the sleeping aid gaboxadol, normalized BBB permeability, showing that sleep deprivation effects on the BBB are reversible. Altering BBB permeability alone through glia-specific suppression of moody, lachesin, or gαo, each a well-studied regulator of BBB function, was sufficient to induce robust sleep phenotypes, demonstrating a tight link between BBB permeability and sleep. Together these studies indicate a role for the BBB as a novel regulatory center for sleep.

Graphical abstract, The epidemic of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection has been listed as a public health emergency of international concern by the World Health Organization (WHO), and its harm degree is defined as a global “pandemic”. At present, the efforts of various countries focus on the rapid diagnosis and isolation of patients, as well as to find a treatment that can combat the most serious impact of the disease. The number of reported COVID-19 virus infections is still increasing. Unfortunately, no drugs or vaccines have been approved for the treatment of human coronaviruses, but there is an urgent need for in-depth research on emerging human infectious coronaviruses. Clarification transmission routes and pathogenic mechanisms, and identification of potential drug treatment targets will promote the development of effective prevention and treatment measures. In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. This review summarizes the epidemiological characteristics, pathogenesis, virus structure and targeting strategies of COVID-19. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19.

The effects of static magnetic field (SMF) on an anoxic/oxic sequencing batch reactor were investigated from the perspective of electron transport via determining the variations of reduced/oxidized nicotinamide adenine dinucleotide (NADH/NAD

Inflammation causing oxidative stress in endothelial cells contributes to heart failure development. Sodium/glucose cotransporter 2 inhibitors (SGLT2i's) were shown to reduce heart failure hospitalization and oxidative stress. However, how inflammation causes oxidative stress in endothelial cells, and how SGLT2i's can reduce this is unknown. Here we hypothesized that 1) TNF-α activates the Na+/H+ exchanger (NHE) and raises cytoplasmatic Na+ ([Na+]c), 2) increased [Na+]c causes reactive oxygen species (ROS) production, and 3) empagliflozin (EMPA) reduces inflammation-induced ROS through NHE inhibition and lowering of [Na+]c in human endothelial cells. Human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) were incubated with vehicle (V), 10 ng/ml TNF-α, 1 µM EMPA or the NHE inhibitor Cariporide (CARI, 10 µM) and NHE activity, intracellular [Na+]c and ROS were analyzed. TNF-α enhanced NHE activity in HCAECs and HUVECs by 92% (p < 0.01) and 51% (p < 0.05), respectively, and increased [Na+]c from 8.2 ± 1.6 to 11.2 ± 0.1 mM (p < 0.05) in HCAECs. Increasing [Na+]c by ouabain elevated ROS generation in both HCAECs and HUVECs. EMPA inhibited NHE activity in HCAECs and in HUVECs. EMPA concomitantly lowered [Na+]c in both cell types. In both cell types, TNF α-induced ROS was lowered by EMPA or CARI, with no further ROS lowering by EMPA in the presence of CARI, indicating EMPA attenuated ROS through NHE inhibition. In conclusion, inflammation induces oxidative stress in human endothelial cells through NHE activation causing elevations in [Na+]c, a process that is inhibited by EMPA through NHE inhibition.

Most online shopping platform firms generate revenue from three sources: pay-per-click search advertising, pay-per-impression display advertising, and membership fees. The strategies that influence these revenue sources typically are studied individually, rather than in a holistic fashion. In response, this study uses time-series data with 18 million buyers and sellers from 2010 to 2011 and undertakes a quasi-experiment to analyze how the distinct effects of buyer- and seller-side strategies on revenues (1) vary across all three revenue sources and (2) depend differentially on a platform’s upmarket repositioning strategy. The results show that buyers that purchase through direct traffic (e.g., typing in the site address) yield more display advertising and membership fee revenues than those gained through organic traffic (e.g., landing from a search engine). Engagement strategies that appeal to established sellers (i.e., value-added services) yield more search advertising and membership revenue than those that appeal to new sellers (i.e., social forums). An upmarket repositioning strategy (i.e., eliminating low quality sellers) enhances the revenue effects of buyer traffic generation and seller engagement strategies. Post hoc analyses suggest that a 1% increase in direct traffic generates an additional $151,506 in display advertising revenue after (vs. before) the repositioning.

Drought, water loss and soil erosion are the main factors restricting grain production and economic development in the semiarid hill areas of Loess Plateau, China. A field experiment was conducted to determine the effects of different tillage systems (open-ridging and tied-ridging) on soil water moisture, runoff, sediment yield, fodder yield and water use efficiency (WUE) on 2 slopes (5° and 10°), using traditional planting (without ridges and furrows) as a control, during 2 consecutive alfalfa growing years: 2015 and 2016. Results indicated that the benefits of fodder yield and WUE increase from tillage system were more effective than the benefits from slope gradient on slight sloping land. Open-ridging and tied-ridging decreased runoff and sediment transport and increased soil moisture, fodder yield and WUE of alfalfa. The decrease of sediment for open-ridging and tied-ridging was 85.1% and 88.4%, respectively, for slopes of 5°, while it was 83.9% and 89.0% for slopes of 10°. Only 7–10% rainfall events produced runoff and 4–6% rainfall events produced sediment. The mean runoff efficiency for traditional planting, open-ridging and tied-ridging was 11.6%, 9.1% and 6.7%, respectively, for slopes of 5°, while it was 13.4%, 10.0% and 7.8% for slopes of 10°, over 2 years. Increase of fodder yields for open-ridging and tied-ridging was 34.6% and 19.8%, respectively, for slopes of 5°, while it was 32.7% and 20.6% for slopes of 10°, over 2 years. The average WUE for open-ridging and tied-ridging was respectively 1.96 and 1.85 times greater than that for traditional planting, for slopes of 5°, while it was 1.88 and 1.77 times greater than that for traditional planting, for slopes of 10°, over 2 years. The mean runoff and sediment for slopes of 10° was 1.14–1.16 and 1.19–1.57 times that for slopes of 5°, respectively. The differences of fodder yield and WUE between slopes of 5° and slopes of 10° were not significant. Tied-ridging rainwater harvesting offered particular effects on water and soil conservation, while open-ridging offered particular effects on fodder yields and WUE enhancement during the first and the second growing seasons.