Highly photoactive Ir(III)-Pt(IV) heterometallic conjugates for anticancer therapy.

For the first time, this study reported the photoactivatable activity of Ir(III)-Pt(IV) heterometallic conjugates, which were stable in the dark and activated to release oxaliplatin and Ir within 3 min of irradiation. The conjugates induced apoptosis and immunologic cell death through Pt-DNA binding and reactive oxygen species generation upon irradiation. This work developed photoactivatable heterometallic agents for anticancer therapy.

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities.

Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.

Exosomal miR­152­5p/ARHGAP6/ROCK axis regulates apoptosis and fibrosis in cardiomyocytes.

Acute myocardial infarction (AMI) is a fatal cardiovascular disease with a high mortality rate. The discovery of effective biomarkers is crucial for the diagnosis and treatment of AMI. In the present study, miRNA sequencing and reverse transcription-quantitative polymerase chain reaction techniques revealed that the expression of exosome derived miR-152-5p was significantly downregulated in patients with AMI compared with healthy controls. A series of functional validation experiments were then performed using H9c2 cardiomyocytes. Following transfection of the cardiomyocytes using an miR-152-5p inhibitor, immunofluorescence staining of a-smooth muscle actin revealed a marked increase in fibrosis. Western blotting revealed that the expression levels of the apoptotic protein Bax, TNF-α and collagen-associated proteins were significantly increased, whereas those of the apoptosis-inhibiting factor Bcl-2 and vascular endothelial growth factor A were significantly decreased. Furthermore, the binding of Rho GTPase-activating protein 6 (ARHGAP6) to miR-152-5p was predicted using an online database and verified using a dual-luciferase reporter gene assay. The transfection of cardiomyocytes with miR-152-5p mimics was found to inhibit the activation of ARHGAP6 and Rho-associated coiled-coil containing kinase 2 (ROCK2). These results suggest that miR-152-5p targets ARHGAP6 through the ROCK signaling pathway to inhibit AMI, which implies that miR-152-5p may be a diagnostic indicator and potential target for treatment of myocardial infarction.

Diversity vs. ingroup: How children generalize for the common good.

How do children generalize for the common good? The present study investigated whether children are more likely to use the preference of their ingroup (ingroup rationale) or that of a diverse group (diversity rationale) as a basis for generalization about the broader community. In a series of studies, five-year-olds from two different cultures (US and China), yet living in environments with analogous ingroup majority-outgroup minority structure, were asked to generalize either the preference of a diverse sample or the preference of an ingroup sample to the majority. We found that children from both cultures have a default strategy to generalize from their ingroup (Study 1). However, Studies 2-4 show that this ingroup default is amenable to change, suggesting that children mostly use this strategy because ingroup members were salient and conveniently available. When ingroup was removed or reduced (Study 2), or when primed with photos of diverse populations (Studies 3 & 4), children changed their strategies and were more likely to use the diversity-rationale. In both cultures, the intergroup structure of children's living environment exerts similar pressures, resulting in analogous outcomes in generalizing for the common good.

From entrepreneurial cognition to entrepreneurial intention and behavior: The case of higher educational institutions in China.

Entrepreneurship has been called "high quality employment" in China. Therefore, universities have paid more attention to entrepreneurship education, which is a crucial element for entrepreneurial success. Based on the theory of "informed intentions" planned behavior and dual cognitive processing theory, this manuscript studies the relationship among entrepreneurial cognition, entrepreneurial intention, recognition perception of university entrepreneurship education, and entrepreneurial behavior from the perspective of mass innovation and mass entrepreneurship in China. The hypotheses are tested using a hierarchical linear regression model based on data from 786 valid questionnaires from more than 400 universities across China. This study finds that student's entrepreneurial cognition positively affects their entrepreneurial behavior, and entrepreneurial intention plays a mediating role by positively strengthening the relationship between these two, and that the recognition perception of university entrepreneurship education strengthens the positive relationship between entrepreneurial intention and entrepreneurial behavior. These findings provide a new perspective and framework for studying the entrepreneurial cognitive education of university students, and they have certain practical implications for the reform of entrepreneurship education in China.

Hybrid Blood Purification in the Treatment of Multiple Organ Dysfunction Syndrome Following a Wasp Attack.

Severe wasp sting symptoms can progress rapidly, often causing multiple organ dysfunction syndrome (MODS) and, in some cases, even death. Early and comprehensive treatment is needed to avoid these outcomes. Here, we report the case of a patient with MODS due to severe wasp stings. The patient received conventional treatment combined with glucocorticoids, plasma exchange, hemoperfusion, and continuous renal replacement therapy and had a successful recovery. MODS is a serious potential complication of wasp stings. Early local wound treatment, antiallergy interventions, antishock therapy, fluid replacement, glucocorticoid administration, and blood purification treatments are required to treat MODS secondary to wasp stings. Our results suggest that a hybrid blood purification method involving plasma exchange combined with hemoperfusion and continuous renal replacement therapy is more clinically effective than the single blood purification method. Early use of high-dose glucocorticoids combined with a hybrid blood purification treatment method had a positive effect in managing our patient and may improve the prognosis of other patients with MODS.

New-onset crescent IgA nephropathy following the CoronaVac vaccine: A case report.

RATIONALE: Although coronavirus disease 2019 (COVID-19) remains a global threat, administering effective and safe vaccines is currently the most promising strategy to curb the ongoing pandemic and decrease the number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. However, there remains some uncertainty regarding the safety of vaccines for patients with kidney disease. PATIENT CONCERNS: A 58-year-old man presented at our institution with gross hematuria 48 hours after receiving his first dose of the CoronaVac (Sinovac) vaccine. DIAGNOSES: Analysis of a renal biopsy sample led to the diagnosis of crescentic immunoglobulin A nephropathy (IgAN), which we considered an adverse event of receiving the CoronaVac vaccine in China. INTERVENTIONS: The patient's serum creatinine and albumin levels were 1.20 mg/dL and 31.3 g/L, respectively; as such, he was administered a diuretic. His serum creatinine level had risen to 7.45 mg/dL 1 month later, and he developed high blood pressure. The patient then received conventional doses of hormone therapy but developed recurrent fever, which led to the suspicion of active tuberculosis (which he had a history of) and suspension of the hormone therapy. OUTCOMES: The patient's renal function deteriorated further, and he ultimately underwent dialysis. LESSONS: The patient's course of events of apparent IgAN exacerbation should prompt nephrologists to closely follow patients with glomerular disease after they receive a COVID-19 vaccine, especially if persistent gross hematuria occurs.

Learning about others and learning from others: Bayesian probabilistic models of intuitive psychology and social learning.

How do infants and young children reason about other people? What inferences do they make when they learn from teachers and whom do they choose to learn from? Past research in developmental psychology has demonstrated infants' and young children's competence in making these inferences. However, the mechanisms underlying these inferences and how these mechanisms change across development are less clear. In this chapter, we review a growing body of Bayesian probabilistic models on intuitive psychology and social learning. We integrate these models with past and new empirical studies within the framework of rational constructivism. These models showed that infants and children have intuitive theories about others (agents, teachers, and informants). When given new evidence, they rationally update their beliefs about others and their beliefs about the world based on these intuitive theories. Developmental changes can be explained by advances in children's intuitive theories. Finally, we propose future directions for both empirical and modeling work in these domains.

Generation of universal natural killer cells from a cryopreserved cord blood mononuclear cell-derived induced pluripotent stem cell library.

Natural killer (NK) cells play a key role in innate immunity and are regarded as a promising candidate for cellular immunotherapy. Natural killer cells may be generated from different sources, including induced pluripotent stem cells (iPSCs); these stem cells produce an abundant amount of NK cells to meet the needs of a wide range of clinical applications. Autologous iPSCs are expensive and labor-intensive to prepare, while allogeneic iPSCs require human leukocyte antigen (HLA) matched cells to avoid the risk of immune rejection. In the current study, we prepared HLA-matched iPSCs using HLA common haplotype homozygous (HLAh) donors from cryopreserved human cord blood (CB) sourced from the Tianjin Cord Blood Public Bank. This approach was designed to generate a CB-derived iPSC library from HLAh donors and use it to produce off-the-shelf NK cells. Starting with readily available cryopreserved CB mononuclear cells (cryoCBMCs), we produced cryoCBMC-derived iPSCs (cryoCB-iPSCs). These cryoCB-iPSCs were induced to generate embryoid bodies (EBs) using an improved 3D suspension culture method, and induced NK (iNK) cells were differentiated from EBs. iNK cells expressed specific surface markers of NK cells, exhibited cytotoxicity comparable with NK cells generated from CB (CB-NK) and peripheral blood (PB-NK), and expressed lower levels of KIRs and HLA-DR compared to CB-NK and PB-NK. Taken together, we have shown that an iPSC library can be established from HLAh cryoCBMCs, and cryoCB-iPSCs can be used to generate a large number of 'universal' NK cells for future clinical applications.

China's NMPA perspective on the clinical performance of SARS-CoV-2 antigen test reagents.

The COVID-19 pandemic continues to spread all over the world. In the process of emergency use authorization, the Center for Medical Device Evaluation of the China National Medical Products Administration issued 'Key Points of Technical Review for the Registration of SARS-CoV-2 Antigen/Antibody Detection Reagents' as the guidance of registration of antigen and antibody test reagents for the industry. In this document, clinical evaluation requirements of antigen detection reagents are elaborated. Based on the Key Points document and the authors' review practice, this article explains the evaluation methods and requirements of clinical performance of SARS-CoV-2 antigen-detecting rapid diagnostic tests, then analyzes the application scenarios and intended use of antigen detection reagents.

Age related changes in cervical range of motion and its relationship with cervical spondylosis in school students aged 12-18 in Nanyang City / 中国学校卫生

Objective@#To investigate the age related changes in cervical range of motion (CROM) and its relationship with cervical spondylosis in school students aged 12-18 in Nanyang City, to provide reference for prevention, early diagnosis and treatment evaluation of cervical spondylosis.@*Methods@#Stratified sampling was adopted in 13 counties and districts of Nanyang City and 890 students aged 12-18 were assessed for CROM using the Coda Motion Analyzer. SPSS 19.0 was used to data analyze.@*Results@#A decreasing trend was observed in CROM among boys and girls aged 12-18 years in Nanyang. For boys aged 15 and 18 years old, higher anterior flexion ( t =2.02, 2.70), posterior extension ( t =2.01, 2.81), left flexion ( t =3.51, 2.99), right flexion ( t =5.07, 2.66), sinistral ( t =2.28, 2.92) and dextral ( t =2.91,3.60) were found compared with younger age groups ( P <0.05). Similar findings were found in girls aged 15 and 18-years old [anterior flexion ( t =2.38, 2.20), posterior extension ( t =2.09,2.02), left flexion ( t =2.33, 2.55), right flexion ( t =7.34, 4.60), sinistral ( t =3.73, 2.35) and dextral ( t =2.31, 3.99, P <0.05). Except for the right flexion, the CROM of boys in was higher than that of girls at the same age group. The prevalence of cervical spondylosis showed an increasing trend (boys: χ 2 trend =13.93, girls: χ 2 trend =12.87, P <0.05). Except for 14-year-old group, the prevalence of cervical spondylosis in girls was higher than that in boys, with significant differences observed in 15 and 17-year-old groups ( χ 2=10.35, 9.64, P <0.05).@*Conclusion@#With the increase of age, the CROM of male and female students shows a downward trend in general. The prevalence of cervical spondylosis increases with the decrease of CROM. CROM measurement is conducive to the prevention, early diagnosis and treatment of juvenile cervical spondylosis.

miR-6718-5p and miR-4329 can be used as potential biomarkers for acute myocardial infarction.

BACKGROUND: The prevention and prognosis of the onset or recurrence of acute myocardial infarction (AMI) is a difficult problem in contemporary research. METHODS: In this study, peripheral blood samples were collected from seven patients with AMI and nine healthy adults, and exosome microRNAs (miRNAs) were extracted. The miRNA differential expression profiles of serum exosomes in patients with AMI were obtained by using the next-generation sequencing technology combined with bioinformatics analysis. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to verify the primary screening of differential exosome miRNAs to reveal the possible mechanism of their action on AMI. RESULTS: Compared with healthy individuals, 544 miRNAs were upregulated and 518 miRNAs were downregulated in AMI patients preoperatively. Among these miRNAs, we selected miR-6718 and miR-4329 for qPCR verification. The expression of miR6718 and miR-4329 in patients with myocardial infarction was significantly lower than that in normal controls.

[Analysis of Cut Off Value or Reference Interval of in Vitro Diagnostic Reagents].

The cut off value or reference interval is significant in clinical testing and diagnosis. If there is no scientific and reasonable cut off value or reference interval for in vitro diagnostic reagents, clinicians can not make medical decisions on patients through the results. The test will be meaningless, so the cut off value or reference interval study is an important part of the preclinical study of in vitro diagnostic reagents. In this article, combined to the review experience of related product, we discuss the establishment and verification of the cut off value and reference interval to provide a reference for relevant manufacturers.

The Effects of Institution-Driven Entrepreneurial Education in Chinese Universities: A Qualitative Comparative Analysis Approach.

Purpose: This study aims to explore the effects of entrepreneurship education by examining the influences of the curriculum system, teaching team, design of practical programs, and the institutional systems on universities' entrepreneurial education performance. Design/Methodology/Approach: This paper employs a case-based approach-Qualitative Comparative Analysis (QCA). Data were collected from 12 universities that were typical cases in the implementation of entrepreneurial education. The four dimensions of entrepreneurship education are applied as conditional indicators. fsQCA3.0 software is used to analyze the necessary conditions and condition combination of the truth table. Findings: There are three sets of condition combinations of the intermediate solution that results in a high level of entrepreneurial education performance: (1) when the credit ratio of entrepreneurship courses is higher and there are more practical platform platforms, even if the entrepreneurship education system and mechanism is less mature, the level of entrepreneurial education performance is high; (2) with a higher credit ratio of entrepreneurship courses, higher quality of teaching teams, and higher standard of practical platforms, the level of entrepreneurial education performance is high; (3) with a higher level of credit ratio of entrepreneurship courses and more practical platforms, as well as mature entrepreneurship education system and mechanism, even if the quality of the teaching team is lower, the level of entrepreneurial education performance is satisfied. Research Limitations/Implications: The dimensions of entrepreneurship education can be expanded; additionally, given that there are many other factors affecting entrepreneurial performance, it is necessary to identify and integrate other possible factors on an ongoing basis. Practical Implications: This study offers practical implications for universities and policy makers that can promote the transformation of theoretical knowledge into practice in the field of entrepreneurship in colleges and universities. Social Implications: This study is one of the first to empirically examine the effect of institutional-driven entrepreneurship education in developing countries. The enhancement of entrepreneurship education can benefit the development of individuals and schools, and even has a potential impact on the progress of the country and society as a whole. Originality/Value: This study emphasizes the significance of viewing the entrepreneurial education as a multi-dimensional concept by targeting different kinds of players. Furthermore, it employs a case-based approach to identify configurations of the antecedent attributes of the curriculum system, teaching team, design of practical programs, and the institutional systems, and their influence on universities' entrepreneurial education performance.

China NMPA perspective on clinical evaluation of SARS-CoV-2 antibody test reagents in the process of emergency approval.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 antibody testing an important supplement to nucleic acid testing. In the process of emergency approval, the Center for Medical Device Evaluation of the China National Medical Products Administration released The Key Points of Technical Review for the Registration of SARS-CoV-2 Antigen/Antibody Detection Reagents. The Clinical Study Requirement section of the Key Point has put forward requirements in terms of reference methods and subject enrolment among others, which can ensure that the test results can meet the clinical needs. This article draws on the experience of the China NMPA in evaluating diagnostic reagents used to supplement the gold standard test method in the early stage of an epidemic of an infectious disease, as well as to serve as reference for clinicians and regulators.

Comparison and application of different immunoassay methods for the detection of SARS-CoV-2.

The detection data of IgM and IgG antibodies in 169 patients with coronavirus disease-2019 (COVID-19) were analyzed to evaluate differences in clinical performance between the colloidal gold method and chemiluminescence method. In this study, chemiluminescence detection of IgM antibody showed a positive conversion earlier (about 1-2 days earlier), positive conversion rates higher in different stages of disease, and a trend of declining positive rate later than colloidal gold method. For IgG antibody, the chemiluminescence method showed a positive conversion earlier and the positive rate climbing more quickly than the colloidal gold method. No obvious negative-converting tendency of IgG detection was observed within 35 days after the onset of disease. Although colloidal gold method is generally less sensitive than chemiluminescence method, it shows advantages of shorter turn-around time, more simple procedure, and no special equipment required. The two methodologies can be chosen according to different laboratory conditions. A reasonable understanding of the performance of reagents with different methodologies can help in clinical disease diagnosis effectively and assist in the diagnosis of the progression of COVID-19, for which the dynamic changes of antibody will provide reliable evidence.

Relating Substructures and Side Effects of Drugs with Chemical-chemical Interactions.

BACKGROUND: Drugs are very important for human life because they can provide treatment, cure, prevention, or diagnosis of different diseases. However, they also cause side effects, which can increase the risks for humans and pharmaceuticals companies. It is essential to identify drug side effects in drug discovery. To date, lots of computational methods have been proposed to predict the side effects of drugs and most of them used the fact that similar drugs always have similar side effects. However, previous studies did not analyze which substructures are highly related to which kind of side effect. METHOD: In this study, we conducted a computational investigation. In this regard, we extracted a drug set for each side effect, which consisted of drugs having the side effect. Also, for each substructure, a set was constructed by picking up drugs owing such substructure. The relationship between one side effect and one substructure was evaluated based on linkages between drugs in their corresponding drug sets, resulting in an Es value. Then, the statistical significance of Es value was measured by a permutation test. RESULTS AND CONCLUSION: A number of highly related pairs of side effects and substructures were obtained and some were extensively analyzed to confirm the reliability of the results reported in this study.

The prognostic values of estrogen receptor alpha and beta in patients with gastroesophageal cancer: A meta-analysis.

BACKGROUND: Published studies have investigated the prognostic roles of estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) in gastroesophageal cancer patients with the controversial results. The aim of the study was to systematically evaluate the impacts of ERα and ERß on the overall survival (OS) in patients. METHOD: Relevant eligible studies were extracted from PubMed, Embase, Web of Science, CNKI and Wanfang databases (from the start date to November 2018) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. HR (hazard ratio) with 95% confidence intervals (CIs) were used to assess the prognostic values of ERα and ERß for OS in patients. RESULTS: High ERα expression was associated with poor OS (HR = 1.58, 95% CI = 1.29-1.94, P < .001) and ERß with better OS (HR = 0.56, 95% CI = 0.37-0.83, P = .004) in gastroesophageal cancer. Furthermore, unfavorable OS was found in Chinese gastroesophageal patients with higher ERα expression (HR = 1.57, 95% CI = 1.25-1.96, P < .001) and better OS with higher ERß expression (HR = 0.51, 95% CI = 0.31-0.83, P < .01) in our subgroup analysis. Meanwhile, worse OS was found in esophageal squamous cell carcinoma (ESCC) patients with high ERα expression (HR = 1.74, 95% CI = 1.33-2.26, P < .001), and favorable OS in ESCC with ERß overexpression (HR = 0.40, 95% CI = 0.31-0.52, P < .001). Besides, high ERα expression was associated with lower tumor differentiation in ESCC (OR = 1.64; 95% CI = 1.02-2.64, P = .04) and ERß was linked with better tumor differentiation in gastric adenocarcinoma (GCA) (OR = 0.49; 95% CI = 0.26-0.94, P = .03). CONCLUSIONS: ERα and ERß might serve as potential prognostic biomarkers for gastroesophageal cancer patients. ERα overexpression predicted poor OS and lower tumor differentiation, and ERß suggested favorable OS and better tumor differentiation. Further related studies should be performed to test these results.

Increased Legumain/Smad3 expression in atherosclerotic plaque of rat thoracic aorta.

OBJECTIVES: The purpose of this study was to investigate the role of legumain in the formation and stability of atherosclerotic plaque, as well as to explore the association between legumain with Smad3 pathway in a rat atherosclerosis model. METHODS: Rat with thoracic aorta atherosclerosis was established and received treatment with statin (n = 15 each) or controls (n = 10). Serum level of legumain was determined by enzyme-linked immunosorbent assay. Legumain and Smad3 aortic expression levels were assessed by immunohistochemistry and fluorescence microscopy. Protein and mRNA levels were analyzed using Western blot analysis and reverse transcriptase coupled polymerase chain reaction, respectively. RESULTS: The atherosclerotic group showed higher serum legumain level than control and statin group. Expression of legumain and Smad3 in macrophages and foam cells was increased in atherosclerotic group compared to control and statin group. The protein and mRNA levels of legumain and Smad3 were significantly attenuated by statin treatment (p < 0.05). For all groups, legumain expression was correlated linearly with Smad3 at mRNA (coefficient: 0.94) and protein (coefficient: 097) level. CONCLUSIONS: Legumain and Smad3 expression is highly expressed in mainly atherosclerotic plaque macrophages and linearly related, which is attenuated by statin therapy, suggesting legumain a potential Smad3 pathway-related marker of atherosclerosis.

Tyrosine phosphorylation activates 6-phosphogluconate dehydrogenase and promotes tumor growth and radiation resistance.

6-Phosphogluconate dehydrogenase (6PGD) is a key enzyme that converts 6-phosphogluconate into ribulose-5-phosphate with NADP+ as cofactor in the pentose phosphate pathway (PPP). 6PGD is commonly upregulated and plays important roles in many human cancers, while the mechanism underlying such roles of 6PGD remains elusive. Here we show that upon EGFR activation, 6PGD is phosphorylated at tyrosine (Y) 481 by Src family kinase Fyn. This phosphorylation enhances 6PGD activity by increasing its binding affinity to NADP+ and therefore activates the PPP for NADPH and ribose-5-phosphate, which consequently detoxifies intracellular reactive oxygen species (ROS) and accelerates DNA synthesis. Abrogating 6PGD Y481 phosphorylation (pY481) dramatically attenuates EGF-promoted glioma cell proliferation, tumor growth and resistance to ionizing radiation. In addition, 6PGD pY481 is associated with Fyn expression, the malignancy and prognosis of human glioblastoma. These findings establish a critical role of Fyn-dependent 6PGD phosphorylation in EGF-promoted tumor growth and radiation resistance.