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Abstract Background It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). Objective To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. Methods In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). Results Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P

Abstract To assess the skiing economy (SE) and kinematics during double poling (DP) roller skiing between two groups of skiers in a field setting. Five experienced and five novice male skiers performed a SEDP test at 16 km∙h−1 on an outdoor athletics track. Gas exchange parameters were measured to determine SEDP. A two-dimensional video was filmed to measure the kinematics variables. Experienced skiers exhibited a 21% lower oxygen cost than novice skiers (p = 0.016) in DP, indicating a strong association between SEDP, cycle length and cycle rate (p

Abstract Thyroid carcinoma (THCA) is the most common endocrine cancer. Phosphodiesterase (PDE) 4 enzyme family, as specific regulator of cyclic adenosine monophosphate, may play a important role in THCA. However, few studies on PDE4 enzyme family in THCA have been reported yet. Therefore, this study aimed to systematically analyze the changes of PDE4 enzyme family in THCA, and look for potential target for THCA therapy. We systematically analyzed the expression differences, prognostic value, genetic alteration, methylation modification, and the correlation with tumor immune microenvironment of PDE4 family in THCA using several public databases, including TCGA, GEO, GSCA, TNMplot, cBioPortal, DiseaseMeth and TIMER. Besides, functional enrichment analysis and protein–protein interaction (PPI) network of PDE4 family was investigated using Metascape and STRING databases. The expression levels of PDE4A, PDE4B and PDE4D were down-regulated in THCA patients at different cancer stages, while the expression level of PDE4C was significantly up-regulated. Moreover, THCA patients with higher PDE4C expression had shorter progress free survival compared with those with lower PDE4C expression. The low genomic alteration frequencies and mildly increased methylation levels of PDE4 family were found in THCA patients. Except for PDE4A, the expression levels of PDE4B, PDE4C and PDE4D could affect many immune cells infiltration during THCA progression. Four PDE4 subtypes were all enriched in cAMP catabolic process. Nevertheless, PDE4C was not enriched in the cAMP binding signal pathway, and PDE4B was not enriched in the G alphas signaling events. Notably, PDE4C participated in cAMP metabolic process by regulating adenylate cyclases (ADCYs), which involved ADCY1, ADCY5, ADCY6, ADCY8 and ADCY9. The findings of this study provide a partial basis for the role of PDE4 family in the occurrence and development of THCA. In addition, this study also suggested that PDE4C might be a potential prognostic marker of THCA, which could serve as a reference for future basic and clinical research.

Elafin, which is derived from trappin-2 or pre-elafin by proteolysis, is an endogenous serine protease inhibitor with a low molecular weight. Its inhibitory activity is dependent on anchoring to the extracellular matrix by forming covalent bonds with its distinctive N-terminal domain via tissue transglutaminases. In addition to inhibiting proteases, it also exhibits anti-inflammatory, antibiotic, antifungal, antiviral and immunomodulatory functions. Elafin plays an important role in inflammatory disease and is a promising candidate for the anti-inflammatory treatment of respiratory diseases. This review will discuss the therapeutic potential of elafin in airway inflammation and provide evidence and suggestions for the future treatment of airway inflammatory diseases. In addition, the therapeutic potential of elafin in lung cancer is also discussed.

Abstract Background The FAST study identified claudin-18 (CLDN18.2) as a promising novel therapeutic target for gastric cancer (GC). However, the tumor immune microenvironment and clinicopathological features of CLDN18.2-positive GC are unclear, making it difficult to develop and optimize CLDN18.2-targeted treatments. Methods This study included 80 GC patients, 60 of whom received anti-PD-1/PD-L1 treatment. CD4/CD8/CD20/CD66b/CD68/CD163/PD-1/PD-L1/TIM-3/LAG-3/FoxP3/CTLA-4/HLA-DR/STING, and CLDN18.2 were labeled using multiplex immunohistochemistry (m-IHC) to decipher the rate and spatial distribution of T cells, B cells, macrophages, and neutrophils in formalin-fixed, paraffin-embedded tumor tissues isolated from these patients. Tumor immune-microenvironmental features and patient survival stratified by CLDN18.2 expression were analyzed using two independent-sample t-tests and log-rank tests, respectively. Results We considered moderate-to-strong CLDN18.2 expression ≥ 40% of tumor cells as the cut-off for positivity. The proportion of CD8+PD-1−, CD8+LAG-3−, and CD8+TIM-3− T cells was significantly higher in CLDN18.2-positive tumors than in negative tumors (0.039 vs. 0.026, P = 0.009; 0.050 vs.0.035, P = 0.024; 0.045 vs. 0.032, P = 0.038, respectively). In addition, the number of neutrophils (CD66b+) was higher in the CLDN18.2-positive group than in the negative group (0.081 vs. 0.055, P = 0.031, respectively), while the rates of M1 (CD68+CD163−HLA-DR+), M2 macrophages (CD68+CD163+HLA-DR−), and B cells (CD20+) were comparable between the CLDN18.2-positive and negative groups. The average numbers of CD8+PD-1−, CD8+LAG-3−, and CD8+TIM-3−T cells surrounding tumor cells within a 20-μm range were higher in CLDN18.2-positive tumors than in the CLDN18.2-negative tumors (0.16 vs. 0.09, P = 0.011; 0.20 vs. 0.12, P = 0.029; 0.18 vs. 0.12, P = 0.047, respectively). In addition, in the CLDN18.2-positive group, tumor cells surrounded by CD8+PD-1−, CD8+LAG-3− T cells, or M1 macrophages within a 20-μm range accounted for a higher proportion of all tumor cells than those in the CLDN18.2-negative group (10.79% vs. 6.60%, P = 0.015; 12.68% vs. 8.70%, P = 0.049; 9.08% vs. 6.56%, P = 0.033, respectively). These findings suggest that CLDN18.2-positive GC harbors complex immune-microenvironmental features. Additionally, CLDN18.2-positive group had shorter OS and irOS than CLDN18.2-negative group (median OS: 23.33 vs.36.6 months, P

High temperature in summer is an unfavorable factor for passion fruit (Passiflora edulis), which can lead to restricted growth, short flowering period, few flower buds, low fruit setting rate, severe fruit drop, and more deformed fruit. To explore the molecular physiology mechanism of passion fruit responding to high-temperature stress, we use ‘Zhuangxiang Mibao’, a hybrid passion fruit cultivar, as the test material. Several physiological indicators were measured and compared between high-temperature (average temperature 38 °C) and normal temperature (average temperature 25 °C) conditions, including photosynthesis, chlorophyll fluorescence parameters, peroxidase activity (POD), superoxide dismutase activity (SOD) and malondialdehyde content. We performed RNA-seq analysis combined with biochemistry experiment to investigate the gene and molecular pathways that respond to high-temperature stress. The results showed that some physiological indicators in the high-temperature group, including the net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, transpiration rate, and the maximum chemical quantum yield of photosystemII (PSII), were significantly lower than those of the control group. Malondialdehyde content was substantially higher than the control group, while superoxide dismutase and superoxide dismutase activities decreased to different degrees. Transcriptome sequencing analysis showed that 140 genes were up-regulated and 75 genes were down-regulated under high-temperature stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis of differentially expressed genes revealed many metabolic pathways related to high-temperature stress. Further investigation revealed that 30 genes might be related to high-temperature stress, such as chlorophyllide a oxygenase (CAO), glutathione (GSH), WRKY transcription factors (WRKY), and heat shock protein (HSP), which have also been reported in other species. The results of real-time fluorescence quantitative PCR and RNA-seq of randomly selected ten genes are consistent, which suggests that the transcriptome sequencing results were reliable. Our study provides a theoretical basis for the mechanism of passion fruit response to high-temperature stress. Also, it gives a theoretical basis for the subsequent breeding of new heat-resistant passion fruit varieties.

Background Preoperative prediction of cervical lymph node metastasis in papillary thyroid carcinoma provided a basis for tumor staging and treatment decision. This study aimed to investigate the utility of machine learning and develop different models to preoperatively predict cervical lymph node metastasis based on ultrasonic radiomic features and clinical characteristics in papillary thyroid carcinoma nodules. Methods Data from 400 papillary thyroid carcinoma nodules were included and divided into training and validation group. With the help of machine learning, clinical characteristics and ultrasonic radiomic features were extracted and selected using randomforest and least absolute shrinkage and selection operator regression before classified by five classifiers. Finally, 10 models were built and their area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, positive predictive value and negative predictive value were measured. Results Among the 10 models, RF-RF model revealed the highest area under curve (0.812) and accuracy (0.7542) in validation group. The top 10 variables of it included age, seven textural features, one shape feature and one first-order feature, in which eight were high-dimensional features. Conclusions RF-RF model showed the best predictive performance for cervical lymph node metastasis. And the importance features selected by it highlighted the unique role of higher-dimensional statistical methods for radiomics analysis.

Abstract Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the world. To investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain (RBD) (PS-RBD) and whole inactivated virus particle vaccine (IV) against the variant strains, in this study, rhesus macaques were immunized with PS-RBD or IV vaccine, followed by a Beta variant (B.1.351) challenge. Although neutralizing activity against the Beta variant was reduced compared with that against the prototype, the decreased viral load in both upper and lower respiratory tracts, milder pathological changes, and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque model. Furthermore, PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha, Beta, Delta, and Omicron variants in our study, though the neutralizing antibody (NAb) titers declined by varying degrees, demonstrating potential protection of PS-RBD against current circulating variants of concern (VOCs). Interestingly, although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant, it still showed reduction for viral load and significantly alleviated pathological change. Other correlates of vaccine-induced protection (CoP) like antibody-dependent cellular cytotoxicity (ADCC) and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.

Abstract Using the Chinese Glioma Genome Atlas (training dataset) and The Cancer Genome Atlas (validation dataset), we found that low-grade gliomas can be divided into two molecular subclasses based on 30 pyroptosis genes. Cluster 1 presented higher immune cell and immune function scores and poorer prognosis than Cluster 2. We established a prognostic model based on 10 pyroptosis genes; the model could predict overall survival in glioma and was well validated in an independent dataset. The high-risk group had relatively higher immune cell and immune function scores and lower DNA methylation levels in pyroptosis genes than the low-risk group. There were no marked differences in pyroptosis gene alterations between the high- and low-risk groups. The competing endogenous RNA (ceRNA) regulatory network uncovered the lncRNA–miRNA–mRNA regulation patterns of the different risk groups in low-grade glioma. Five pairs of target genes and drugs were identified. In vitro, CASP8 silencing inhibited the migration and invasion of glioma cells. The expression of pyroptosis genes can reflect the molecular biological and clinical features of low-grade glioma subclasses. The developed prognostic model can predict overall survival and distinguish molecular alterations in patients. Our integrated analyses could provide valuable guidelines for improving risk management and therapy for low-grade glioma patients.

Abstract Variants are globally emerging very quickly following pandemic prototypic SARS-CoV-2. To evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants, we vaccinated rhesus monkeys with three doses of prototypic SARS-CoV-2 inactivated vaccine, followed by challenging with emerging SARS-CoV-2 variants of concern (VOCs). These vaccinated animals produced neutralizing antibodies against Alpha, Beta, Delta, and Omicron variants, although there were certain declinations of geometric mean titer (GMT) as compared with prototypic SARS-CoV-2. Of note, in vivo this prototypic vaccine not only reduced the viral loads in nasal, throat and anal swabs, pulmonary tissues, but also improved the pathological changes in the lung infected by variants of Alpha, Beta, and Delta. In summary, the prototypic SARS-CoV-2 inactivated vaccine in this study protected against VOCs to certain extension, which is of great significance for prevention and control of COVID-19.

Current COVID-19 vaccines are effective countermeasures to control the SARS-CoV-2 virus pandemic by inducing systemic immune responses through intramuscular injection. However, respiratory mucosal immunization will be needed to elicit local sterilizing immunity to prevent virus replication in the nasopharynx, shedding, and transmission. In this study, we first compared the immunoprotective ability of a chimpanzee replication–deficient adenovirus–vectored COVID-19 vaccine expressing a stabilized pre–fusion spike glycoprotein from the ancestral SARS-CoV-2 strain Wuhan–Hu–1 (BV-AdCoV-1) administered through either aerosol inhalation, intranasal spray, or intramuscular injection in cynomolgus monkeys and rhesus macaques. Compared with intranasal administration, aerosol inhalation of BV-AdCoV-1 elicited stronger humoral and mucosal immunity that conferred excellent protection against SARS-CoV-2 infection in rhesus macaques. Importantly, aerosol inhalation induced immunity comparable to that obtained by intramuscular injection, although at a significantly lower dose. Furthermore, to address the problem of immune escape variants, we evaluated the merits of heterologous boosting with an adenovirus–based Omicron BA.1 vaccine (C68–COA04). Boosting rhesus macaques vaccinated with two doses of BV-AdCoV-1 with either the homologous or the heterologous C68–COA04 vector resulted in cross–neutralizing immunity against WT, Delta, and Omicron subvariants, including BA.4/5 stronger than that obtained by administering a bivalent BV-AdCoV-1/C68–COA04 vaccine. These results demonstrate that the administration of BV-AdCoV-1 or C68–COA04 via aerosol inhalation is a promising approach to prevent SARS-CoV-2 infection and transmission and curtail the pandemic spread.

Abstract Tobacco bacterial wilt (TBW) is seriously damages the growth of tobacco. There is an urgent need to find a safer and more effective measure to control TBW. In this study, B. amyloliquefaciens ZM9 and marigold powder were applied to the tobacco roots alone or in combination, and the potential inhibition of TBW was assessed. On the other hand, the effects of these treatments on soil physicochemical properties, rhizosphere microbial community and soil metabolites were also evaluated. The results showed that the application of B. amyloliquefaciens ZM9 or marigold powder alone significantly reduced the abundance of R. solanacearum in rhizosphere soil, while the integrated treatment showed the strongest inhibitory effect. Moreover, the integrated treatment can inhibit the secretion of chemoattractants, and affect the change of rhizosphere soil microbial composition. In conclusion, the combination of antagonistic bacteria agent B. amyloliquefaciens ZM9 with marigold powder can enhance the suppression of TBW. Furthermore, B. amyloliquefaciens ZM9 and marigold have synergistic effects on suppressing TBW by regulation soil physicochemical properties, soil metabolites and microbial structure. This study provide a promising strategy for TBW control by integrated applying of B. amyloliquefaciens ZM9 and marigold powder.

Objectives To assess participants’ satisfaction with and predictors of upper gastrointestinal cancer screening in rural areas.Design Cross-sectional study.Setting Ten screening centres in seven cities across five provinces in China.Participants Of the 452 participants screened during the survey period, 438 completed the survey (response rate: 96.90%).Primary outcome measures Screening satisfaction was the primary outcome and it was assessed using the Patient Satisfaction Questionnaire-18. Ordinal logistic regression analysis was used to analyse the predictors of satisfaction.Results The percentages of satisfaction with the General Satisfaction, Technical Quality, Interpersonal Manner, Communication, Financial Aspects, Time Spent With Doctor, and Convenience and Accessibility dimensions were 95.89%, 79.68%, 88.36%, 83.56%, 75.11%, 82.19% and 66.44%, respectively. Education (OR 0.25, 95% CI 0.07 to 0.90), health self-assessment (OR 15.29, 95% CI 2.86 to 81.78) and family history of cancer (OR 4.20, 95% CI 1.29 to 13.71) were associated with General Satisfaction. Residence (OR 4.31, 95% CI 1.89 to 9.81) was associated with Technical Quality. Occupation (OR 0.27, 95% CI 0.08 to 0.88), health self-assessment (OR 11.30, 95% CI 3.94 to 32.43), screening purpose (OR 0.18, 95% CI 0.03 to 0.92) and distance from the screening centre (OR 4.59, 95% CI 1.35 to 15.61) were associated with interpersonal manner. Gender (OR 1.85, 95% CI 1.02 to 3.34), residence (OR 3.23, 95% CI 1.23 to 8.53) and endoscopy in the previous year (OR 2.79, 95% CI 1.13 to 6.90) were associated with Communication. Body mass index (BMI; OR 5.06, 95% CI 1.40 to 18.25) and health self-assessment (OR 2.09, 95% CI 1.12 to 3.88) were associated with financial aspects. Gender (OR 1.90, 95% CI 1.07 to 3.38), residence (OR 3.19, 95% CI 1.30 to 7.79), BMI (OR 5.26, 95% CI 1.14 to 24.34) and health self-assessment (OR 2.14, 95% CI 1.06 to 4.34) were associated with time spent with doctor. Gender (OR 1.64, 95% CI 1.04 to 2.60) and residence (OR 3.17, 95% CI 1.46 to 6.88) were associated with convenience and accessibility.Conclusion There was heterogeneity across the dimensions of satisfaction with rural upper gastrointestinal cancer screening. Project manager should prioritise improving the aspects related to the convenience and accessibility dimension. Furthermore, to improve the efficiency of potential interventions, the predictors of the various dimensions should be considered.

Current knowledge regarding the long-term humoral response of people infected with human immunodeficiency virus to the third dose of inactivated coronavirus disease (COVID-19) vaccine is incomplete. As a result, concerns remain about the safety and efficacy of the vaccination. To improve our understanding of the safety and immunogenicity of the COVID-19 inactivated vaccine booster in people living with HIV (PLWH), a prospective study was conducted on participants who had not yet received a third dose of the COVID-19 inactivated vaccine, had no history of SARS-CoV-2 infection, and had received a second dose of the vaccine more than six months prior. The primary safety outcomes included the incidence of adverse reactions, changes in CD4+ T-cell count, viral load, blood routine examination, liver and kidney function examination, blood sugar, and blood lipid examination. The pseudovirus-neutralizing antibody responses to the D614G variant, Delta variant, and Omicron variants BA.5 and BF.7 were evaluated before vaccination, 14 days, 28 days, 3 months, and 6 months after vaccination to evaluate the immune response of PLWH to the injection of inactivated vaccine booster and the safety of the vaccine. In conclusion, COVID-19 vaccine booster shots were effective in PLWH, resulting in an increase in the number of CD4+ T-cells, neutralizing antibodies that lasted up to six months, and higher levels of neutralizing antibodies lasting approximately 3 months. However, the vaccine protection against the two variants of BA.5 and BF.7 was significantly lower than that of D614G and Delta.

Abstract Tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum is the most serious soil-borne disease of tobacco. However, molecular mechanism information of R. solanacearum resistance is limited to tobacco, hindering better breeding of resistant tobacco. In this study, the expression profiles of the rootstalks of Yunyan87 (susceptible cultivar) and Fandi3 (resistant cultivar) at different stages after R. solanacearum infection were compared to explore molecular mechanisms of tobacco resistance against the bacterium. Findings from gene-expression profiling indicated that the number of upregulated differentially expressed genes (DEGs) at 3 and 7 days post-inoculation (dpi) increased significantly in the resistant cultivar. WRKY6 and WRKY11 family genes in WRKY transcription factors, ERF5 and ERF15 family genes in ERFs transcription factors, and genes encoding PR5 were significantly upregulated in the resistant cultivar response to the infection. For the first time, WRKY11 and ERF15 were found to be possibly involved in disease-resistance. The Kyoto Encyclopedia of Genes and Genomes analysis demonstrated glutathione metabolism and phenylpropane pathways as primary resistance pathways to R. solanacearum infection. In the resistant cultivar, DEGs encoding CYP450, TCM, CCoAOMT, 4CL, PAL, CCR, CSE, and CADH, involved in the synthesis of plant antitoxins such as flavonoids, stilbenoids, and lignins, enriched in the phenylpropane pathway were upregulated at 3 and 7 dpi. Furthermore, a pot experiment was performed to verify the role of flavonoids in controlling TBW. This study will strongly contribute to a better understanding of molecular interactions between tobacco plants and R. solanacearum.

Abstract Bacterial wilt as a soil-borne disease was caused by Ralstonia solanacearum, and seriously damages the growth of tobacco. Integrated biocontrol method was explored to control bacterial wilt. Nevertheless, the long-term effects of the integrated biocontrol method on soil bacterial community, soil physicochemical properties and the incidence of bacterial wilt are not well understood. In this study, B. amyoliquefaciens ZM9, calcium cyanamide and rice bran were applied to tobacco fields in different ways. The disease index and incidence of tobacco bacterial wilt (TBW), soil physicochemical properties, colonization ability of B. amyoliquefaciens ZM9, and rhizopshere bacterial community were investigated. The results showed that the integrated application of B. amyoliquefaciens ZM9, rice bran and calcium cyanamide had the highest control efficiency of TBW and bacteria community diversity. Additionally, the integrated biocontrol method could improve the colonization ability of B. amyoliquefaciens ZM9. Furthermore, the integrated biocontrol method could effectively suppress TBW by regulating soil physicochemical properties, promoting beneficial bacteria and antagonistic bacteria of rhizopshere soil. This strategy has prospect of overcoming the defects in application of a single antagonistic bacteria and provides new insights to understand how to improve the colonization capacity of antagonistic bacteria and control efficacy for TBW.

Many studies have shown that Histone deacetylases (HDAC) is involved in the occurrence of malignant tumors and regulates the occurrence, proliferation, invasion, and migration of malignant tumors through a variety of signaling pathways. In the present, we explored the role of Histone deacetylases genes in prognosis and immune response in low-grade glioma. Using consensus clustering, we built the new molecular clusters. Using HDAC genes, we constructed and validated the prognostic model in two independent cohort datasets. Patients were divided into high-risk and low-risk groups. Then, we explored the molecular characteristics, clinical characteristics, tumor microenvironment and immune infiltration levels of two clusters and risk groups. Receiver operating characteristic analyses were built for model assessment. We finally detected the expression levels of signature genes between tumor and normal tissues. Low-grade can be separated into two molecular clusters using 11 HDACs genes. Two clusters had different clinical characteristics and prognosis. Nex, we constructed a prognosis model using six HDAC genes (HDAC1, HDAC4, HDAC5, HDAC7, HDAC9, and HDAC10), which was also validated in an independent cohort dataset. Furthermore, multivariate cox regression indicated that the calculated risk score was independently associated with prognosis in low-grade glioma, and risk score can predict the five-year survival probability of low-grade glioma well. High-risk patients can be attributed to multiple complex function and molecular signaling pathways, and the genes alterations of high- and low-risk patients were significantly different. We also found that different survival outcomes of high- and low- risk patients could be involved in the differences of immune filtration level and tumor microenvironment. Subsequently, using signature genes, we identified several small molecular compounds that could be useful for low-grade glioma patients' treatment. Finally, we detected the expression levels of signature genes in tumor tissues. our study uncovers the biology function role of HDAC genes in low-grade glioma. We identified new molecular subtypes and established a prognostic model based on six HDAC genes, which was well applied in two independent cohort data. The regulation of HDAC genes in low-grade glioma involved in multiple molecular function and signaling pathways and immune infiltration levels. Further experiments in vivo and vitro were required to confirm the present findings.

Soil erosion has a severe impact on habitat and productivity. It is considered to be a major environmental threat prevalent in ecosystems. However, few researchers have studied the spatial distribution of soil erosion intensity among different geographic environmental factors. The Qin River Basin is a geographical unit consisting of mountains, hills, and plains with significant regional characteristics, and it has a basin area of 14,810.91 km2. This study uses the Geographical Information Systems, Revised Universal Soil Loss Equation model to analyze the spatiotemporal changes in the soil-erosion intensity in the Qin River Basin from 1990 to 2018. Different environmental factors of land use, slope and altitude on erosion intensities of 19 secondary land types were analyzed. It can better reflect the soil erosion under different environmental factors and different land use types. Results show that the soil erosion modulus of Qin River Basin were 10.25 t hm-2 a-1, and it belong to slight erosion from 1990 to 2018. Soil erosion intensity is greater in grassland and woodland than in cropland. The strongest soil erosion occurred in the sparse forestland, and the lowest was in beach land. Soil erosion was the highest for a slope of 15~25° and an altitude of 1200~1500 m. Rainfall and slope are important factors lead to soil erosion, indicating weak water and soil conservation implemented in these areas. Therefore, priority should be given to these geomorphic units to formulate and implement soil-erosion control and ecological restoration policies in the Qin River Basin. This study provides a good reference for preventing and controlling soil erosion in river basins.

Climate is a dominant factor affecting the potential geographical distribution of species. Understanding the impact of climate change on the potential geographic distribution of species, which is of great significance to the exploitation, utilization, and protection of resources, as well as ecologically sustainable development. Betula platyphylla Suk. is one of the most widely distributed temperate deciduous tree species in East Asia and has important economic and ecological value. Based on 231 species distribution data points of Betula platyphylla Suk. in China and 37 bioclimatic, soil, and topography variables (with correlation coefficients < 0.75), the potential geographical distribution pattern of Betula platyphylla Suk. under Representative Concentration Pathway (RCP) climate change scenarios at present and in the 2050s and 2070s was predicted using the MaxEnt model. We analyzed the main environmental variables affecting the distribution and change of suitable areas and compared the scope and change of suitable areas under different climate scenarios. This study found: (1) At present, the main suitable area for Betula platyphylla Suk. extends from northeastern to southwestern China, with the periphery area showing fragmented distribution. (2) Annual precipitation, precipitation of the warmest quarter, mean temperature of the warmest quarter, annual mean temperature, and precipitation of the driest month are the dominant environmental variables that affect the potential geographical distribution of Betula platyphylla Suk. (3) The suitable area for Betula platyphylla Suk. is expected to expand under global warming scenarios. In recent years, due to the impact of diseases and insect infestation, and environmental damage, the natural Betula platyphylla Suk. forest in China has gradually narrowed. This study accurately predicted the potential geographical distribution of Betula platyphylla Suk. under current and future climate change scenarios, which can provide the scientific basis for the cultivation, management, and sustainable utilization of Betula platyphylla Suk. resources.

Hemophilia B is a bleeding disorder caused by a deficiency of coagulation factor IX (FIX). Treatment with FIX replacement products can increase FIX activity levels to minimize or prevent bleeding events. However, frequent dosing with standard-acting FIX products can create a high treatment burden. Long-acting products have been developed to maintain bleed protection with extended dosing intervals. Recombinant factor IX–albumin fusion protein (rIX-FP) is a long-acting product indicated for the treatment and prophylaxis of bleeding events and perioperative management in adult and pediatric patients. This review outlines data from all previously treated patients in the Prophylaxis and On-Demand Treatment using Longer Half-Life rIX-FP (PROLONG-9FP) clinical trial program and summarizes real-world data evaluating the use of rIX-FP in routine clinical practice. In the PROLONG-9FP program, rIX-FP demonstrated effective hemostasis in all patients at dose regimens of up to 21 days in patients aged ≥ 18 years and up to 14 days in patients aged < 12 years. rIX-FP has a favorable pharmacokinetic profile and an excellent safety and tolerability profile. Extended dosing intervals with rIX-FP led to high levels of adherence and reduced consumption compared with other FIX therapies. Data from real-world practice are encouraging and reflect the results of the clinical trials.

Background Colorectal cancer (CRC) is the third most common cancer in the world. The present study is aimed at identifying hub genes associated with the progression of CRC. Method The data of the patients with CRC were obtained from the Gene Expression Omnibus (GEO) database and assessed by weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses performed in R by WGCNA, several hub genes that regulate the mechanism of tumorigenesis in CRC were identified. Differentially expressed genes in the data sets GSE28000 and GSE42284 were used to construct a co-expression network for WGCNA. The yellow, black and blue modules associated with CRC level were filtered. Combining the co-expression network and the PPI network, 15 candidate hub genes were screened. Results After validation using the TCGA-COAD dataset, a total of 10 hub genes (MT1X, MT1G, MT2A, CXCL8, IL1B, CXCL5, CXCL11, IL10RA, GZMB, KIT) closely related to the progression of CRC were identified. The expressions of MT1G, CXCL8, IL1B, CXCL5, CXCL11 and GZMB in CRC tissues were higher than normal tissues (p-value < 0.05). The expressions of MT1X, MT2A, IL10RA and KIT in CRC tissues were lower than normal tissues (p-value < 0.05). Conclusions By combinating with a series of methods including GO enrichment analysis, KEGG pathway analysis, PPI network analysis and gene co-expression network analysis, we identified 10 hub genes that were associated with the progression of CRC.

[This corrects the article DOI: 10.1371/journal.pone.0176954.].

A genetic algorithm (GA) cannot always avoid premature convergence, and multi-population is usually used to overcome this limitation by dividing the population into several sub-populations (sub-population number) with the same number of individuals (sub-population size). In previous research, the questions of how a network structure composed of sub-populations affects the propagation rate of advantageous genes among sub-populations and how it affects the performance of GA have always been ignored. Therefore, we first propose a multi-population GA with an ER network (MPGA-ER). Then, by using the flexible job shop scheduling problem (FJSP) as an example and considering the total individual number (TIN), we study how the sub-population number and size and the propagation rate of advantageous genes affect the performance of MPGA-ER, wherein the performance is evaluated by the average optimal value and success rate based on TIN. The simulation results indicate the following regarding the performance of MPGA-ER: (i) performance shows considerable improvement compared with that of traditional GA; (ii) for an increase in the sub-population number for a certain TIN, the performance first increases slowly, and then decreases rapidly; (iii) for an increase in the sub-population size for a certain TIN, the performance of MPGA-ER first increases rapidly and then tends to remain stable; and (iv) with an increase in the propagation rate of advantageous genes, the performance first increases rapidly and then decreases slowly. Finally, we use a parameter-optimized MPGA-ER to solve for more FJSP instances and demonstrate its effectiveness by comparing it with that of other algorithms proposed in other studies.

Abstract Background Squamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characterize PDX models using biopsy tissue from advanced esophageal cancer patients to lay the foundation of preclinical application. Methods Fresh endoscopic biopsy tissues were harvested from patients with advanced esophageal cancer and implanted subcutaneously into NOD/SCID mice. Then, the PDXs were serially passaged for up to four generations. Transplantation was analyzed and genomic characteristics of xenografts were profiled using next-generation sequencing. Results Twenty-five PDX models were established (13.3%, 25/188). The latency period was 75.12 ± 19.87 days (50–120 days) for the first passage and it decreased with increasing passaging. Other than tumor stages, no differences were found between transplantations of xenografts and patient characteristics, irrespective of chemotherapy. Histopathological features and chemosensitivity of PDXs were in great accordance with primary patient tumors. Each PDX was assessed for molecular characteristics including copy number variations, somatic mutations, and signaling pathway abnormalities and these were similar to patient results. Conclusions Our PDX models were established from real time biopsies and molecularly profiled. They might be promising for drug development and individualized therapy.

Ribosome-inactivating proteins (RIPs) are toxic proteins that can inhibit protein synthesis. RIPs purified from Bougainvillea have low nonspecific toxicity, showing promise for processing applications in the agricultural and medical fields. However, systematic research on the polymorphism of Bougainvillea RIPs is lacking, and it is worth exploring whether different isoforms differ in their active characteristics. The transcriptional and translational expression of type I RIPs in Bougainvillea glabra leaves was investigated in this study. Seven RIPs exhibited seasonal variation at both the mRNA and protein levels. The isoforms BI4 and BI6 showed the highest transcriptional expression in both the summer and autumn samples. Interestingly, BI6 was not detected in the protein level in any of the samples. However, the bioinformatics analysis showed that RIPs derived from the same species were gathered in a different cluster, and that the active sites changed among the isoforms during evolution. The significant discrepancy in Bougainvillea RIPs mainly locates at both termini of the amino acid sequence, particularly at the C terminus. Post-translational modifications may also exist in Bougainvillea RIPs. It is concluded that the reason for the polymorphism of Bougainvillea RIPs may be that these proteins are encoded by multiple genes due to genetic processes such as gene duplication and mutation. According to the results of sequence analysis, the possible functional differences of B. glabra RIP isoforms are discussed with regard to the observed discrepancy in both active sites and structures.

Abstract Favorable prospects for the exploration of shale gas have been demonstrated in the Ordos Basin, China. Outcrop and core observations indicate that there are abundant laminas in the shale strata, which exert a great influence on hydro-fracture propagation, gas storage and fluid flow. In this study, the continental shale of the Chang 72 Member, collected from the south of Ordos Basin, was investigated to characterize the geometric heterogeneity. Laminas at multiple scales were observed and measured using conventional logging, borehole TV, core analysis, scanning electron microscopy, and the Particle and Crack Analysis System. These measurement tools correspond to the meter scale, decimeter scale, centimeter scale, millimeter scale and ten-micrometer scale, respectively, with measured thicknesses of 2.26 m, 2.09 dm, 1.70 cm, 1.48 mm and 11.70 μm, respectively. Fractal theory was used to analyze the power exponent distribution of the lamina thickness, with a resulting fractal dimension of 1.06. Finally, a geometric heterogeneity model was proposed for the Upper Triassic Yanchang Formation in the study area and verified by a modeled thickness of 26.30 m for the Chang 72 Member at the 10-m scale. The model facilitates cross-scale analysis and provides parameter guidance for heterogeneity characterization in the numerical simulation and model test of the shale gas reservoir.

Abstract Obesity causes low-grade inflammation that is involved in male infertility. Interleukin 1 beta (IL1β) plays an important role in this process. A high-fat diet (HFD) is the most common cause of obesity. However, the effect of a HFD on IL1β and its consequence in reproduction remain unclear. We established a HFD model in mice treated at immature stage (mice-TIS) and mice treated at mature stage (mice-TMS). Surprisingly, we found that a HFD decreased IL1β levels and was accompanied by an increase in testosterone in mice-TIS, while the reverse results were observed in mice-TMS. In addition, a HFD caused a reduction in testis macrophages and in the expression of inflammasome-related genes and proteins in mice-TIS. Furthermore, we found that IL1β inhibited testosterone secretion through down-regulating the gene expression of P450SCC and P450c17. However, the influence on mice-TIS that were induced by a HFD was recovered by stopping the HFD. In this study, we are the first to report that a HFD impairs the reproductive system by decreasing IL1β and enhancing testosterone levels in mice-TIS, which are different from the effects in mice-TMS. This provides new ideas for the treatment of obesity-induced infertility.

Rhesus macaque is an important animal model in biomedical research, especially human disease, developmental, translational, and pre-clinical research. Blood physiological and biochemical parameters are important markers for physiology, pathology, and toxicology research. However, these parameters have not been systematically reported for Chinese rhesus macaques. To characterize the reference for these parameters, this study collected 1805 Chinese rhesus macaques living in Southwestern China. A total of 24 blood physiological indexes and 27 biochemical parameters were determined. Sex and age were found to affect these parameters. In conclusion, a comprehensive and systematic reference of hematological and biochemical parameters for Chinese rhesus macaque was established in this work on the basis of a large cohort. Such reference will benefit biomedical research employing rhesus macaques as animal models.

The authors wish to make the following corrections to their paper [...]

Bacillus thuringiensis (Bt) is a gram negative soil bacterium. This bacterium secretes various proteins during different growth phases with an insecticidal potential against many economically important crop pests. One of the important families of Bt proteins is vegetative insecticidal proteins (Vip), which are secreted into the growth medium during vegetative growth. There are three subfamilies of Vip proteins. Vip1 and Vip2 heterodimer toxins have an insecticidal activity against many Coleopteran and Hemipteran pests. Vip3, the most extensively studied family of Vip toxins, is effective against Lepidopteron. Vip proteins do not share homology in sequence and binding sites with Cry proteins, but share similarities at some points in their mechanism of action. Vip3 proteins are expressed as pyramids alongside Cry proteins in crops like maize and cotton, so as to control resistant pests and delay the evolution of resistance. Biotechnological- and in silico-based analyses are promising for the generation of mutant Vip proteins with an enhanced insecticidal activity and broader spectrum of target insects.

A fast and robust interpolation filter based on finite difference TPS has been proposed in this paper. The proposed method employs discrete cosine transform to efficiently solve the linear system of TPS equations in case of gridded data, and by a pre-defined weight function with respect to simulation residuals to reduce the effect of outliers and misclassified non-ground points on the accuracy of reference ground surface construction. Fifteen groups of benchmark datasets, provided by the International Society for Photogrammetry and Remote Sensing (ISPRS) commission, were employed to compare the performance of the proposed method with that of the multi-resolution hierarchical classification method (MHC). Results indicate that with respect to kappa coefficient and total error, the proposed method is averagely more accurate than MHC. Specifically, the proposed method is 1.03 and 1.32 times as accurate as MHC in terms of kappa coefficient and total errors. More importantly, the proposed method is averagely more than 8 times faster than MHC. In comparison with some recently developed methods, the proposed algorithm also achieves a good performance.

Previous studies confirmed that dietary supplements of fish oil and krill oil can alleviate obesity in mice, but the underlying mechanism remains unclear. This study aims to discern whether oil treatment change the structure of the gut microbiota during the obesity alleviation. The ICR mice received high-fat diet (HFD) continuously for 12 weeks after two weeks of acclimatization with a standard chow diet, and the mice fed with a standard chow diet were used as the control. In the groups that received HFD with oil supplementation, the weight gains were attenuated and the liver index, total cholesterol, triglyceride and low-density lipoprotein cholesterol were reduced stepwise compared with the HFD group, and the overall structure of the gut microbiota, which was modulated in the HFD group, was shifted toward the structure found in the control group. Moreover, eighty-two altered operational taxonomic units responsive to oil treatment were identified and nineteen of them differing in one or more parameters associated with obesity. In conclusion, this study confirmed the effect of oil treatment on obesity alleviation, as well as on the microbiota structure alterations. We proposed that further researches are needed to elucidate the causal relationship between obesity alleviation and gut microbiota modulation.

We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.A slight male predominance was detected in these patients (59.0%). Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54) cases with KRAS mutations in 16.7% (9/54) cases and Nras mutations in 5.4%(3/54) cases. BRAF V600E mutation was detected in 3.7% (2/54) cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9%) cases were composed of ≥50% signet-ring cells; 22 (36.1%) cases were composed of

Chromogranin A (CgA), present in the chromaffin granules of neuroendocrine cells, is a useful biomarker for the diagnosis of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This study was conducted to investigate the potential role of circulating CgA in monitoring clinical response in Chinese patients with advanced GEP-NETs. Eighty patients with advanced GEP-NETs treated in Peking University Cancer Hospital from September 2011 to May 2014 and 65 healthy individuals were included in this study. Serum CgA levels were analyzed for relationship with patient's baseline characteristics and clinical outcome. Median CgA levels were significantly higher in patients with advanced GEP-NETs than in healthy individuals (93.8 ng/mL vs. 37.1 ng/mL; P

Lipid A is the active center of lipopolysaccharide which also known as endotoxin. Monophosphoryl-lipid A (MPLA) has less toxicity but retains potent immunoadjuvant activity; therefore, it can be developed as adjuvant for improving the strength and duration of the immune response to antigens. However, MPLA cannot be chemically synthesized and can only be obtained by hydrolyzing lipopolysaccharide (LPS) purified from Gram-negative bacteria. Purifying LPS is difficult and time-consuming and can damage the structure of MPLA. In this study, Escherichia coli mutant strains HWB01 and HWB02 were constructed by deleting several genes and integrating Francisella novicida gene lpxE into the chromosome of E. coli wild type strain W3110. Compared with W3110, HWB01 and HWB02 synthesized very short LPS, Kdo2-monophosphoryl-lipid A (Kdo2-MPLA) and Kdo2-pentaacyl-monophosphoryl-lipid A (Kdo2-pentaacyl-MPLA), respectively. Structural changes of LPS in the outer membranes of HWB01 and HWB02 increased their membrane permeability, surface hydrophobicity, auto-aggregation ability and sensitivity to some antibiotics, but the abilities of these strains to activate the TLR4/MD-2 receptor of HKE-Blue hTLR4 cells were deceased. Importantly, purified Kdo2-MPLA and Kdo2-pentaacyl-MPLA differed from wild type LPS in their ability to stimulate the mammalian cell lines THP-1 and RAW264.7. The purification of Kdo2-MPLA and Kdo2-pentaacyl-MPLA from HWB01 and HWB02, respectively, is much easier than the purification of LPS from W3110, and these lipid A derivatives could be important tools for developing future vaccine adjuvants.

BACKGROUND:Left ventricular hypertrophy (LVH) was suggested to be an important risk factor for hypertensive vascular complications. Previous studies had also shown that red cell distribution width (RDW) was associated with morbidity and mortality of cardiovascular disease. However, few have yet investigated possible association between RDW and LVH. The aim of the present study was to evaluate the relationship between LVH and RDW levels in hypertensive patients. METHODS:Physical examination, laboratory tests and echocardiography were conducted in 330 untreated newly diagnosed hypertensive patients attending the cardiology consultation unit at the Anzhen Hospital of Beijing. The multivariate logistic regression model was used to verify the independent association between RDW and LVH. RESULTS:174 patients without LVH and 156 patients with LVH were rolled in the study. The patients with LVH had higher mean SBP, albumin to creatinine ratio, total cholesterol, RDW and fasting glucose compared with non-LVH group. The mean HDL-cholesterol level was significantly lower in patients with LVH than patients without LVH. The multiple logistic regression model suggested that patients with a higher RDW level were more likely to be LVH (OR=2.187, 95%CI: 1.447-3.307, P

Advances in research relating to pulmonary embolisms (PE) can assist physicians in selecting the best management strategies for PE patients. However, the symptoms, signs, disease history, lesion position and pathophysiology linked to different genders in patients with PE have rarely been evaluated. One hundred and forty-nine PE patients (73 males and 76 females) were sequentially recruited to this study over the last five years whilst attending our Emergency Department. Data relating to the symptoms, signs, disease history, biochemical testing, cardiac electrophysiology, imaging detection, treatment and outcome were collected and the gender differences were analyzed. We found that embolisms occurred significantly more frequently in the right lung (89.7%) than in the left lung (42.6%). The presence of dyspnea, the number of patients presenting with tumors, the number of patients with chronic pulmonary disease, those with emboli in the right pulmonary artery and emboli in the right lung, as well as the average systolic and diastolic blood pressure were: 78.1%, 15.1%, 31.5%, 32.9%, 94.5%, 129.9+20.0 and 75.0+11.2 in the male patients and 59.2%, 1.3%, 14.5%, 17.1%, 69.7%, 125.1+14.6 and 69.3+11.0 in the female patients. These indicators were found to be significantly higher in male patients. In contrast, the rate of V1-V4 T-wave inversion and level of D-dimer in the blood were significantly lower in males than in females. No significant difference was observed in the remaining observational indicators. Gender differences regarding the symptoms, signs, disease history, lesion position and pathophysiology exist in patients with PE and should be considered in clinical practice.

BACKGROUND AND AIMS: MET, the hepatocyte growth factor receptor, is a receptor tyrosine kinase overexpressed and activated in a subset of gastric cancer. Several studies investigated the relationship between MET amplification and expression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. We performed a systematic review and meta-analysis to determine the influence of MET amplification and expression on prognosis in gastric cancer. METHODS: MEDLINE and EMBASE were searched for studies that explored the association between MET amplification and expression with survival in patients with gastric cancer up to 1 April, 2013. Data of individual hazard ratios (HRs) and 95% confidence intervals (CIs) for meta-analyses were extracted from the publications and combined in pooled HRs. RESULTS: Fourteen studies involving 2,258 patients with gastric cancer were included. It was suggested that MET overexpression had an unfavorable impact on survival of patients with gastric cancer, with HRs (95% CIs) of 2.57 (95% CI: 1.97-3.35) overall, 2.82 (95% CI: 1.86-4.27) among studies using amplification for measure scale of MET and 2.42 (95% CI: 1.66-3.54) for expression. The magnitude of association was reduced whereas remained statistically significant in high quality studies or in larger sample size studies and corresponding HRs were 2.18(1.76, 2.70) and 2.35(1.93, 2.87), respectively, without significant heterogeneity. CONCLUSION: The findings from present study indicated that higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis.

In bacteria, threonine dehydratases could convert L-threonine to 2-ketobutyrate. Some threonine dehydratases contain only a catalytic domain, while others contain an N-terminal catalytic domain and a C-terminal regulatory domain composed of one or two ACT-like subdomains. However, the role of the ACT-like subdomain in threonine dehydratases is not clear. Here, nine different bacterial threonine dehydratases were studied. Three of the nine contain no ACT-like subdomain, four of them contain a single ACT-like subdomain, and two of them contain two ACT-like subdomains. The nine genes encoding these threonine dehydratases were individually overexpressed in E. coli BL21(DE3), and the enzymes were purified to homogeneity. Activities of the purified enzymes were analyzed after incubation at different temperatures and different pHs. The results showed that threonine dehydratases with a single ACT-like subdomain are more stable at higher temperatures and a broad range of pH than those without ACT-like subdomain or with two ACT-like subdomains. Furthermore, the specific activity of threonine dehydratases increases with the increase of the number of ACT-like subdomains they contain. The results suggest that the ACT-like subdomain plays an important role in bacterial threonine dehydratases.

To seek accurate and credible correlation manner between gender, age, and obesity; and the severity of obstructive sleep apnea (OSA) in large-scale population.Totals of 1,975 male and 378 female OSA patients were sequentially recruited. Centralized covariant tendencies between age, body mass index (BMI), and waist hip ratio (WHR); and OSA severity, were explored in a gender-specific manner via multiple statistical analyses. The accuracies of observed correlations were further evaluated by adaptive multiple linear regression.All of age, BMI, WHR, smoking, drinking, and OSA severity differed between males and females. BMI and WHR were positively and (approximately) linearly associated with OSA severity in both males and females. Restricted cubic spline analysis was more effective than was the Pearson correlation approach in correlating age with AHI, and provided age crossover points allowing further piecewise linear modeling for both males and females. Multiple linear regression showed that increasing age was associated with OSA exacerbation in males aged ≤ 40 years and in females aged 45-53 years. BMI, WHR, and diabetes were independently associated with OSA severity in males with age-group-specific pattern. In females, only BMI was associated with OSA severity at all ages.In male patients, BMI and WHR are prominent risk factors for OSA exacerbation. Age and diabetes are associated with OSA severity in males of particular ages. In females, BMI is also a prominent risk factor for severe OSA, and OSA severity increased with age in the range 45-53 years.

Aberrant epigenetic nuclear reprogramming results in low somatic cloning efficiency. Altering epigenetic status by applying histone deacetylase inhibitors (HDACi) enhances developmental potential of somatic cell nuclear transfer (SCNT) embryos. The present study was carried out to examine the effects of Oxamflatin, a novel HDACi, on the nuclear reprogramming and development of bovine SCNT embryos in vitro. We found that Oxamflatin modified the acetylation status on H3K9 and H3K18, increased total and inner cell mass (ICM) cell numbers and the ratio of ICM∶trophectoderm (TE) cells, reduced the rate of apoptosis in SCNT blastocysts, and significantly enhanced the development of bovine SCNT embryos in vitro. Furthermore, Oxamflatin treatment suppressed expression of the pro-apoptotic gene Bax and stimulated expression of the anti-apoptotic gene Bcl-XL and the pluripotency-related genes OCT4 and SOX2 in SCNT blastocysts. Additionally, the treatment also reduced the DNA methylation level of satellite I in SCNT blastocysts. In conclusion, Oxamflatin modifies epigenetic status and gene expression, increases blastocyst quality, and subsequently enhances the nuclear reprogramming and developmental potential of SCNT embryos.

Abstract Background In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students’ performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students’ academic self-efficacy. Methods The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students’ satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. Results The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students’ learning ability and the duration of students’ autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students’ learning burden have been identified as the primary factors influencing their preference for future teaching method. Conclusions Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students’ participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.