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Since May 2022, Monkeypox virus (MPXV) cases have dramatically increased worldwide. In this comprehensive review, we describe the basic characteristics, transmission routes, and susceptible individuals of MPXV as well as discuss the main causes of the current outbreak. The history, clades, genetic evolution, and transmission tendency of MPXV are depicted. Regarding viral transmission analysis in several geographical spots, we would like to point out that men who have sex with men (MSM) could play important roles in the process of transmission that eventually causes viral outbreaks. Susceptible populations at high risk of infection alert society to raise awareness on the protection of these special individuals. We also highlight that airline traveling is a driving force in causing international MPXV transmission. Further summarization of the clinical implications, the prevention of MPXV, and clinical measures of viral detection can enable the rapid diagnosis of MPXV.

Persimmon (Diospyros kaki Thunb.) contains numerous uridine diphosphate glucosyltransferases (UGT), and their roles in fruit development and quality formation have not been well studied because of limited genetic information. This study investigated a persimmon DkUGT3 which is highly expressed in young fruits and leaves during development. DkUGT3 can catalyze ABA glycosylation to form ABA-GE, thereby reducing free ABA. Tomato with overexpressed (OE) DkUGT3 significantly induces pale green color phenotypes in both transgenic young plants and fruits. DkUGT3-OE significantly weakens the tomato ABA signaling which affects the expressions of ABA-inducible transcriptional factors (TFs), such as GLK1 and GLK2 and their downstream target genes involved in chlorophyll synthesis, chloroplast development, sugar metabolism and transport, and photosynthesis, thereby impeding leaf and fruit development and quality. Conversely, DkUGT3-RNAi-treatment recovered the OE tomato fruits from yellowing phenotype to green color. This study found that chlorophyll accumulations and ABA level were increased by DkUGT3-RNAi-treatment in young persimmon leaves. These results demonstrate that DkUGT3 plays crucial roles in ABA-mediated leaf and fruit development. This study provides new evidence for the regulation of ABA in early development.

Breast cancer, as a highly heterogeneous malignant tumor, is one of the primary causes of death among females worldwide. The etiology of breast cancer involves aberrant epigenetic mechanisms and abnormal expression of certain non-coding RNA (ncRNAs). DNA methylation, N6-methyladenosine(m6A), and histone methylation are widely explored epigenetic regulation types in breast cancer. ncRNAs are a group of unique RNA transcripts, mainly including microRNA (miRNAs), long non-coding RNA (lncRNAs), circular RNA (circRNAs), small interfering RNA (siRNAs), piwi-interacting RNA (piRNAs), etc. Different types of methylation and ncRNAs mutually regulate and interact to form intricate networks to mediate precisely breast cancer genesis. In this review, we elaborate on the crosstalk between major methylation modifications and ncRNAs and discuss the role of their interaction in promoting breast cancer oncogenesis. This review can provide novel insights into establishing a new diagnostic marker system on methylation patterns of ncRNAs and therapeutic perspectives of combining ncRNA oligonucleotides and phytochemical drugs for breast cancer therapy.

Abscisic acid (ABA) regulates plant development mainly through its signaling, in which ABA binds to receptors to inhibit type 2C protein phosphatases (PP2Cs). The exact roles of PP2Cs in fruit development are still unclear. In this work, we verify that tomato SlPP2C5 works as a negative regulator in ABA signaling during fruit development. SlPP2C5 was inhibited by both monomeric and dimeric ABA receptors SlPYLs through ABA dose–dependent way, and it interacted physically with SlPYLs and SlSnRK2s. SlPP2C5 was highly expressed in fruits induced by exogenous ABA. Plants with overexpressed SlPP2C5 had lower sensitivity to ABA, which showed faster seed germination and primary root growth compared to Wild type (WT), while SlPP2C5-suppressed plants were more sensitive to ABA. SlPP2C5-over-expression (OE) delayed fruit ripening onset, while SlPP2C5-RNAi advanced fruit ripening. Alteration of SlPP2C5 expression impacts fruit quality parameters as well, including pericarp thickness, fruit shape index, seed number and weight and the soluble solid content. RNA-seq analysis revealed that there were significant expression differences of genes related to ethylene release and lycopene synthesis between WT and both SlPP2C5-OE and SlPP2C5-RNAi lines with an inversed variation. Taken together, our findings demonstrate that SlPP2C5 plays an important role in the regulation of fruit development, ripening and quality.

Academic burnout of basic education is widespread in varying degrees in the global scope, and such situation is particularly serious in Chinese primary and secondary schools. International research has rarely mentioned the concept of academic burden, which is mainly described in other similar concepts, such as academic burnout, academic stress, academic depression and academic anxiety. In addition, studies in other countries have paid more attention to the negative influence of academic load on students’ body and mind. Based on international perspective, the paper clarifies the somatic and psychological symptoms, behavior and attitude symptoms and symptoms of academic burnout caused by heavy academic burden, analyzes the influence factors of academic burden, and compares the function and applied scope of inventories and scales for academic burden. Findings enlighten us to focus on the teaching situations and students’ nature, increase empirical research and quantitative research of academic burden, put forward evidence-based, operational and pragmatic strategy of alleviating academic burden.

For a long time, the U.S. government has paid great attention to gifted education, issuedmany educational acts and standardized about gifted education, whichprovides high effect in the fields of theory, model and practice of gifted education. From the perspective of industrialization of Educationof giftedness and practice of gifted education teachers, six aspects of standards are analyzed, including studying and development, identification and evaluation, curriculum and teaching, learning environment, project implementation and professional development of gifted education teachers. Combining the actual conditions of gifted education in China, several enlightenment could be drawn as setting goals by educational outputs, adhering to fair principle, paying attention to growth environment, focusing on professional development, perfecting the systems of evaluation and supportinggifted programming for expecting long-term returns.

Alveolar type II (AT II) is a key structure of the distal lung epithelium and essential to maintain normal lung homeostasis. Dedifferentiation of AT II cells is significantly correlated with lung tumor progression. However, the potential molecular mechanism and clinical significance of AT II-associated genes for lung cancer has not yet been fully elucidated. In this study, we comprehensively analyzed the gene expression, prognosis value, genetic alteration, and immune cell infiltration of eight AT II-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1, and PGC) in Nonsmall Cell Lung Cancer (NSCLC). The results have shown that the expression of eight genes were remarkably reduced in cancer tissues and observably relating to clinical cancer stages. Survival analysis of the eight genes revealed that low-expression of CLDN18, FOXA2, NKX2-1, PGC, SFTPB, SFTPC, and SFTPD were significantly related to a reduced progression-free survival (FP), and low CLDN18, FOXA2, and SFTPD mRNA expression led to a short postprogression survival (PPS). Meanwhile, the alteration of 8 AT II-associated genes covered 273 out of 1053 NSCLC samples (26%). Additionally, the expression level of eight genes were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells. In summary, this study provided clues of the values of eight AT II-associated genes as clinical biomarkers and therapeutic targets in NSCLC and might provide some new inspirations to assist the design of new immunotherapies.

Phytohormone abscisic acid (ABA) regulates the growth and development of plants as well as their response to environmental changes. Recently, the regulations of ABA during fruit ripening and stress resistance were discovered in two types of fruits (climacteric and non-climacteric fruits). However, it is challenging to understand the physiological, biochemical, and molecular biological mechanisms in fruit ripening and stress response controlled by ABA. ABA is involved in fruit development processes, including young fruit growth, fruit ripening onset, ripening process and quality formation. Meanwhile, ABA plays an important role in fruit adapting to environmental stresses. ABA works through the adjustment of its concentration and signal transduction. This review summarizes the current knowledge regarding ABA in the regulation of fruit development and ripening as well as in responses to environmental stresses.

Abscisic acid (ABA) plays a vital role in coordinating physiological processes during fresh fruit ripening. Binding of ABA to receptors facilitates the interaction and inhibition of type 2C phosphatase (PP2C) co-receptors. However, the exact mechanism of PP2C during fruit ripening is unclear. In this study, we determined the role of the tomato ABA co-receptor type 2C phosphatase SlPP2C3, a negative regulator of ABA signaling and fruit ripening. SlPP2C3 selectively interacted with monomeric ABA receptors and SlSnRK2.8 kinase in both yeast and tobacco epidermal cells. Expression of SlPP2C3 was ABA-inducible, which was negatively correlated with fruit ripening. Tomato plants with suppressed SlPP2C3 expression exhibited enhanced sensitivity to ABA, while plants overexpressing SlPP2C3 were less sensitive to ABA. Importantly, lack of SlPP2C3 expression accelerated the onset of fruit ripening and affected fruit glossiness by altering the outer epidermis structure. There was a significant difference in the expression of cuticle-related genes in the pericarp between wild-type and SlPP2C3-suppressed lines based on RNA sequencing (RNA-seq) analysis. Taken together, our findings demonstrate that SlPP2C3 plays an important role in the regulation of fruit ripening and fruit glossiness in tomato.

Background There have been few studies on CYP2C19 genotypes and clopidogrel response associated with ischemic stroke (IS), especially IS complicated by type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association between CYP2C19 polymorphisms and high on-treatment platelet reactivity (HTPR) in IS patients with T2DM in China. Patients and Methods A total of 426 consecutive IS patients with T2DM were enrolled in this case-control study and they were divided into HTPR group and non-HTPR group according to the ADP-induced platelet inhibition (PIADP) assessed by thromboelastography (TEG). Genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Various clinical and demographic data were also recorded. The association between CYP2C19 genetic variants and platelet function was assessed. Results Carriers of CYP2C19*2 heterozygous and mutant homozygous genotypes showed significantly lower PIADP than non-carriers (27.2% vs 38.3%, p < 0.001; 27.41% vs 38.3%, p = 0.012, respectively). Compared with the control group, the CYP2C19*2 A allele was more frequent in the HTPR group (34.51% vs 25.82%, p = 0.002). The carriage of CYP2C19*2 mutant allele was significantly associated with increased risk of HTPR (odds ratio (OR) = 1.94, 95% confidence interval (CI) = 1.32-2.85). There was no significant correlation between CYP2C19*3 or *17 genotypes and HTPR risk. Conclusion CYP2C19*2 mutant allele was associated with attenuated platelet response to clopidogrel and increased risk of HTPR in IS patients with T2DM, suggesting that CYP2C19*2 polymorphism might be an important predictor of HTPR in this high-risk population.

Hepatic diseases include all diseases that occur in the liver, including hepatitis, cirrhosis, hepatocellular carcinoma, etc. Hepatic diseases worldwide are characterized by high incidences of digestive system diseases, which present with subtle symptoms, are difficult to treat and have high mortality. Galectins are β-galactoside-binding proteins that have been found to be aberrantly expressed during hepatic disease progression. An increasing number of studies have shown that abnormal expression of galectins is extensively involved in hepatic diseases, such as hepatocellular carcinoma (HCC), liver cirrhosis, hepatitis and liver fibrosis. Galectins function as intracellular and extracellular hepatic disease regulators mainly through the binding of their carbohydrate recognition domain to glycoconjugates expressed in hepatocytes. In this review, we summarize current research on the various roles of galectins in cirrhosis, hepatitis, liver fibrosis and HCC, which may provide a preliminary theoretical basis for the exploration of new targets for the treatment of hepatic diseases.

The aim of the present study was to evaluate the antitumor effects of 2,2',4'-trihydroxychalcone (7a) on the A549 human lung cancer cell line. A549 cells were treated with different concentrations of 7a for different time periods. Cells without 7a were used as the negative control group. Cell proliferation, invasion, vasculogenic mimicry (VM) formation, heterogeneous adhesion and apoptosis were measured using Cell Counting Kit-8, Transwell invasion, VM, adhesion and flow cytometric assays, respectively. In addition, the expression of related proteins was determined using western blot analysis or ELISA. The present study found that 7a had a significant inhibitory effect on the survival rate of the A549 lung cancer cells but almost no effect on BEAS-2B human lung epithelial cells or human venous endothelial cells. The migration rate, VM length, invasion rate and heterogeneous adhesion number of cells treated with 7a significantly decreased as the concentration increased, while the apoptosis rate increased. Western blot analysis showed that 7a treatment significantly increased the expression levels of E-cadherin, cleaved poly (ADP-ribose) polymerase, Bax and caspase-3 and simultaneously decreased the expression levels of metalloproteinase-2/9, Bcl-2, phosphorylated (p)-PI3K, p-AKT, p-mTOR, vascular endothelial growth factor (VEGF), E-selectin and N-cadherin. At the same time, the ELISA results showed that the level of the pro-angiogenic factor VEGF in the culture media was reduced in the presence of 7a. In addition, 7a could also reduce the nuclear NF-κB protein expression, which could inhibit the gene transcription of tumor apoptosis and metastasis-related proteins. Therefore, 7a may exert inhibitory effects on A549 cells by inhibiting cell proliferation, migration, VM formation and heterogeneous adhesion, as well as by inducing apoptosis through the suppression of the PI3K/AKT/NF-κB signaling pathway; these findings suggested that 7a may be a promising agent for the treatment of lung cancer.

Invasive growth of glioblastoma makes residual tumor unremovable by surgery and leads to disease relapse. Temozolomide is widely used first-line chemotherapy drug to treat glioma patients, but development of temozolomide resistance is almost inevitable. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is found to be related to temozolomide response of gliomas. However, whether inducing ferroptosis could affect invasive growth of glioblastoma cells and which ferroptosis-related regulators were involved in temozolomide resistance are still unclear. In this study, we treated glioblastoma cells with RSL3, a ferroptosis inducer, in vitro (cell lines) and in vivo (subcutaneous and orthotopic animal models). The treated glioblastoma cells with wild-type or mutant IDH1 were subjected to RNA sequencing for transcriptomic profiling. We then analyze data from our RNA sequencing and public TCGA glioma database to identify ferroptosis-related biomarkers for prediction of prognosis and temozolomide resistance in gliomas. Analysis of transcriptome data from RSL3-treated glioblastoma cells suggested that RSL3 could inhibit glioblastoma cell growth and suppress expression of genes involved in cell cycle. RSL3 effectively reduced mobility of glioblastoma cells through downregulation of critical genes involved in epithelial-mesenchymal transition. Moreover, RSL3 in combination with temozolomide showed suppressive efficacy on glioblastoma cell growth, providing a promising therapeutic strategy for glioblastoma treatment. Although temozolomide attenuated invasion of glioblastoma cells with mutant IDH1 more than those with wild-type IDH1, the combination of RSL3 and temozolomide similarly impaired invasive ability of glioblastoma cells in spite of IDH1 status. Finally, we noticed that both ferritin heavy chain 1 and ferritin light chain predicted unfavorable prognosis of glioma patients and were significantly correlated with mRNA levels of methylguanine methyltransferase as well as temozolomide resistance. Altogether, our study provided rationale for combination of RSL3 with temozolomide to suppress glioblastoma cells and revealed ferritin heavy chain 1 and ferritin light chain as biomarkers to predict prognosis and temozolomide resistance of glioma patients.

Background: Lung cancer is one of the most commonly diagnosed cancer and the leading cause of cancer-related death in the world. ATⅡ（alveolar type II cells, ATⅡ ）are a key structure of the distal lung epithelium and have a secretory function that is essential to maintain normal lung homeostasis. ATⅡ cells dedifferentiate into a cell stem-like state, which can continuous differentiation, proliferation, repair and damage, and helps initiate and maintain tumor progression. However, the potential mechanistic value of ATⅡ-associated genes as a clinical biomarker and therapeutic target of NSCLC has not been fully elucidated.Methods: We used the Gene Expression Profile Interaction Analysis (GEPIA) and Oncomine database to explore the expression of ATⅡ-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC) in NSCLCpatients. Then we euse the Kaplan Meierplotter and the GEPIA website to evaluate the prognosis of survival impact of differential expression of these genes. Finally, we analyzed the correlation between eight ATⅡ-associated genes and infiltration of immune cells using the TIMER website.Results: The expression levels of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC were remarkably reduced in lung cancer tissues, and also observably related to clinical cancer stages. Low mRNA expression of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC were associated with short overall survival (OS) in NSCLS patients and the low expression of CLDN18, FOXA2, NKX2-1, PGC, SFTPB, SFTPC, SFTPD were significantly related to a reduced progression-free survival (FP), and low CLDN18, FOXA2 and SFTPD mRNA expression led to a short post-progression survival (PPS). Moreover, the functions of the differentially expressed eight ATⅡ-associated genes were primarily related to lung development, regulation of epithelial to mesenchymal transition, late endosome, antibacterial humoral response. Finally, the expression of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC in LUAD and LUSC patients were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells.Conclusion: Our study provided strong evidence of the values of ATⅡ-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC) as clinical biomarkers and therapeutic targets in NSCLC and might provide some new inspirations to assist in the design of new immunotherapies.

AbstractGrowing evidence reveals that microorganisms in the gut are linked to metabolic health and disease risk in human beings to a considerable extent. The focus of research at this stage must tend to focus on cause-and-effect studies. In addition to being a component of DNA and RNA, purine metabolites can be involved in purine signalling in the body as chemical messengers. Abnormalities in purinergic signalling may lead to neuropathy, rheumatic immune diseases, inflammation, tumors, and a wide range of other diseases. It has proved that gut microbes are involved in purinergic signalling. The relationship between these gut-derived purinergic signalling molecules and host metabolism may be one of the important clues to our understanding of the mechanisms by which the microbiota affects host metabolism.

OBJECTIVE: The purpose of this review is to clarify the potential roles of forkhead box transcription factor M1 (FoxM1) in the occurrence and progression of breast cancer, as well as the predictive value of FoxM1 as a prognostic biomarker and potential therapeutic target for breast cancer. BACKGROUND: Breast cancer, well-known as a molecularly heterogeneous cancer, is still one of the most frequently diagnosed malignant tumors among females worldwide. Tumor recurrence and metastasis are the central causes of high mortality in breast cancer patients. Many factors contribute to the occurrence and progression of breast cancer, including FoxM1. FoxM1, widely regarded as a classic proliferation-related transcription factor, plays pivotal roles in the occurrence, proliferation, invasion, migration, drug resistance, and epithelial-mesenchymal transition (EMT) processes of multiple human tumors including breast cancer. METHODS: The PubMed database was searched for articles published in English from February 2008 to May 2021 using related keywords such as “forkhead box transcription factor M1”, “human breast cancer”, “FoxM1”, and “human tumor”. About 90 research papers and reports written in English were identified, most of which were published after 2015. These papers mainly concentrated on the functions of FoxM1 in the occurrence, development, drug resistance, and treatment of human breast cancer. CONCLUSIONS: Considering that the abnormal expression of FoxM1 plays a significant role in the proliferation, invasion, metastasis, and chemotherapy drug resistance of breast cancer, and its overexpression is closely correlated with the unfavorable clinicopathological characteristics of breast tumor patients, it is considerably important to comprehend the regulatory mechanism of FoxM1 in breast cancer. This will provide strong evidence for FoxM1 as a potential biomarker for the targeted treatment and prognostic evaluation of breast cancer patients.

Objectives：Our study aimed to evaluate the antitumor effects of 2,2',4'-trihydroxychalcone (7a) on human lung cancer cell line A549. Methods：A549 cells were treated with different concentrations of 7a for different times. The cells without 7a were set as the negative control group. The cell proliferation, invasion, vasculogenic mimicry (VM) formation, heterogeneous adhesion, apoptosis were, respectively, measured by CCK-8, transwell invasion assay, vasculogenic mimicry assay, adhesion assay and flow cytometry. In addition, the expression of related proteins were examined via western blot or ELISA. Results：Our research found that 7a had a significant inhibitory effect on the survival rate of lung cancer A549 cells, while almost had no effect on human lung epithelial BEAS-2B cells and human venous endothelial cells (HUVECs). The migration rate, VM length, invasion and heterogeneous adhesion number of cells treated with 7a significantly decreased as the increase in concentration, while the apoptosis rate increased. Western blot analysis showed that 7a treatment significantly upregulated the expression of E-cadherin, cleaved PARP, Bax, caspase-3, and simultaneously downregulated the expression of MMP-2/9, Bcl-2, p-PI3K, p-Akt, p-MTOR, VEGF, E-selectin and N-cadherin. At the same time, ELISA results found that the pro-angiogenic factor VEGF level in culture media was reduced in the presence of 7a. Additionally, 7a could also reduce the nucleus NF-κB protein level, which would inhibit gene transcription of tumor activity-related proteins. Conclusion：7a might exert inhibitory effects on A549 cells via inhibiting cell proliferation, migration, VM formation, heterogeneous adhesion and inducing apoptosis through suppressing the PI3K/AKT/NF-κB signaling pathway, suggesting that 7a might have therapeutic potential for the treatment of lung cancer.

In recent years, it is urgent and challenging to fabricate highly sensitive and selective gas sensors for breath analyses. In this work, Sr-doped cubic In2O3/rhombohedral In2O3 homojunction nanowir...

Abscisic acid (ABA) regulates fruit ripening, yet little is known about the exact roles of ABA receptors in fruit. In this study, we reveal the role of SlPYL9, a tomato pyrabactin resistance (PYR)/pyrobactin resistance-like (PYL)/regulatory component of ABA receptors (RCAR) protein, as a positive regulator of ABA signaling and fruit ripening. SlPYL9 inhibits protein phosphatase-type 2C (PP2C2/6) in an ABA dose-dependent way, and it interacts physically with SlPP2C2/3/4/5 in an ABA-dependent manner. Expression of SlPYL9 was observed in the seeds, flowers, and fruits. Overexpression and suppression of SlPYL9 induced a variety of phenotypes via altered expression of ABA signaling genes (SlPP2C1/2/9, SlSnRK2.8, SlABF2), thereby affecting expression of ripening-related genes involved in ethylene release and cell wall modification. SlPYL9-OE/RNAi plants showed a typical ABA hyper-/hypo-sensitive phenotype in terms of seed germination, primary root growth, and response to drought. Fruit ripening was significantly accelerated in SlPYL9-OE by 5–7 d as a result of increased endogenous ABA accumulation and advanced release of ethylene compared with the wild-type. In the SlPYL9-RNAi lines, fruit ripening was delayed, mesocarp thickness was enhanced, and petal abscission was delayed compared with the wild-type, resulting in conical/oblong and gourd-shaped fruits. These results suggest that SlPYL9 is involved in ABA signaling, thereby playing a role in the regulation of flower abscission and fruit ripening in tomato., ABA receptor PYL9 plays a role in the regulation of flower abscission and fruit ripening in tomato by modulating ABA signaling components, which regulates expression of related genes.

Serum thyroid stimulating hormone (TSH) detection is of great clinical significance in monitoring thyroid function. The aim of the present study was to establish reference intervals (RIs) for serum TSH in healthy Han population in Southwest China using data from routine health check-up individuals.Healthy subjects (n = 7,116) were enrolled from January 2019 to September 2020. Serum TSH values were determined in the Beckman Coulter UniCel™ DxI 800 Access® immunoassay system. Outliers were identified and removed using Dixon's interactive principle. The 95th percentile range was calculated as RIs for serum TSH. All the statistical analyses were run on R statistical software version 4.0.3.A total of 6,668 (1,324 female and 5,344 male) suitable individuals were included in this study. Serum TSH results showed a non-Gaussian distribution by Kolmogorov-Smirnov test. According to Mann-Whitney U analysis, the serum TSH values for the female group differ from the male group's (p0.05). Besides, Spearman's rank correlation test disclosed that no obvious correlation was observed between serum TSH levels and age (r = -0.0039, p0.05). Accordingly, the RIs for serum TSH in Southwest China Han population were 0.64 (95% CI: 0.62 to 0.65) to 4.05 (95% CI: 4.02 to 4.09) mIU/L in male and 0.72 (95% CI: 0.67 to 0.77) to 5.66 (95% CI: 5.58 to 5.75) mIU/L in female, respectively.In this study, the laboratory specific RIs for serum TSH were successfully established by indirect method using the data from health check-up population. It implies that the indirect method is an easy and lowcost pathway for each laboratory to establish its own RIs.

Objective. To explore the mechanisms of ursolic acid for treating colon cancer based on network pharmacology. Method. In this study, the potential targets of ursolic acid against colon cancer were predicted and screened through the TCMSP, SYMMAP, Drug Bank, UNI-PROT, and DISGENET databases. The protein interaction (PPI) network was constructed based on the STRING database, and graphs were drawn with the help of Cytoscape software. GO and KEGG enrichment analyses were performed on the targets by using the DAVID database for biological information annotation. Results. Ursolic acid has 113 targets in the treatment of colon cancer. The core targets included interleukin-6 (IL-6), mitogen-activated protein kinase 3 (MAPK3), vascular endothelial growth factor receptor (VEGFA), prostaglandin endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 8 (MAPK8), tumor necrosis factor (TNF), cyclin D1 (CCND1), JUN, signal transducer and transcriptional activator 3 (STAT3), and other targets. The first 10 pathways related to colon cancer were screened out. The main signaling pathways included the TNF signaling pathway and the AGE-RAGE signaling pathway in diabetic complications and human colon cancer infections. Conclusion. This study revealed that ursolic acid played a multitarget and multichannel antitumor role by inhibiting the proliferation of tumor cells, inducing apoptosis, and enhancing antiangiogenesis.

Galectin-3 (gal-3), a member of the galectin family, is a glycoprotein with high affinity for β-galactoside. Gal-3 is a cytoplasmically synthesized protein that can shuttle between the cytoplasm and nucleus and can even be transported to the membrane and secreted into the extracellular environment. Cardio/cerebrovascular diseases generally refer to ischemic or hemorrhagic diseases occurring in the heart, brain and systemic tissues, which are characterized by high morbidity, high disability rates and high mortality rates. To date, considerable research has demonstrated that gal-3 expression is aberrantly increased and plays important roles in cardio/cerebrovascular diseases, such as acute ischemic stroke (AIS), myocardial fibrosis, acute coronary syndrome (ACS), and heart failure (HF). Hence, understanding the biological roles of gal-3 in these diseases may be essential for cardio/cerebrovascular disease treatment and diagnosis to improve patient quality of life. In this review, we summarize current research on the roles of gal-3 in human cardiovascular diseases and potential inhibitors of gal-3, which may provide new strategies for disease therapies.

Global myocardial work (MW) analysis by pressure-strain loops (PSL) allows the non-invasive assessment of left ventricular (LV) function. We aimed to investigate the relationship between LV global MW and the degree of coronary artery stenosis in suspected coronary artery disease (CAD) patients with normal LV ejection fraction and regional wall motion. A total of 164 suspected CAD patients were divided into four groups according to coronary artery angiography. The results showed that global work efficiency (GWE) as the most significant predictor in all MW parameters had the optimal cut-off value of 94.5% for detecting moderate stenosis, and the sensitivity and specificity was 89.7% and 85.8%, respectively. A cut-off value of 94.0% for GWE was the most significant predictor of severe stenosis, and the sensitivity and specificity was 81.4% and 76.1%, respectively. In conclusion, LV global MW is a sensitive tool in detecting the degree of coronary artery stenosis and a potential valuable method to provide early diagnosis for CAD patients.

Abscisic acid (ABA) plays a vital role in coordinating physiological processes during fresh fruit ripening. ABA can bind to ABA receptors which interacts and inhibits their co-receptors type 2C phosphatases (PP2Cs). However, the dissected mechanism of PP2C during fruit ripening is unclear. In this study, we identify the role of SlPP2C3, a tomato type 2C phosphatase, as a negative regulator of ABA signaling and fruit ripening. SlPP2C3 selectively interacted with monomeric ABA receptors and SlSnRK2.8 kinase in both yeast and tobacco epidermal cells. Expressions of SlPP2C3 were observed in all tissues, and it negatively correlated with the fruit ripening which was induced by exogenous ABA. Tomato plants with suppressed SlPP2C3 expression exhibited enhanced sensitivity to ABA, while SlPP2C3 over-expressed plants were less sensitive to ABA. Meaningfully, lack of SlPP2C3 expression causes the acceleration of fruit ripening onset via the alternation of ABA signaling activity, and the fruit gloss is affected by the changes of outer epidermis structure. RNA-seq analysis found significant different expression of cuticle-related genes in pericarp between wild-type and SlPP2C3 suppressed lines. Taken together, our finding demonstrate that SlPP2C3 plays an important role in the regulation of fruit ripening and fruit appearance quality in tomato.

Despite significant advances in transplantation, acute cellular rejection (AR) remains a major obstacle that is most prevalent in the first months post heart transplantation (HT). Current treatments require high doses of immunosuppressive drugs followed by maintenance therapies that have systemic side effects including early infection. In this study, we attempted to prevent AR with a myocardial-targeted galectin-7-siRNA delivery method using cationic microbubbles (CMBs) combined with ultrasound targeted microbubble destruction (UTMD) to create local immunosuppression in a rat abdominal heterotopic heart transplantation acute rejection model.Galectin-7-siRNA (siGal-7) bound to CMBs were synthesized and effective ultrasound-targeted delivery of siGal-7 into target cells confirmed in vitro. Based on these observations, three transplant rat models were tested：①isograft (ISO); ② Allograft (ALLO) +UTMD; and ③ALLO + PBS. UTMD treatments were administered at 1, 3, 5, 7 days after HT. Galectin 7 expression was reduced by 50% compared to ALLO + PBS (p 0.005), and this was associated with significant reductions in both galectin 7 and Interleukin-2 protein levels (p 0.001). The ALLO + UTMD group had Grade II or less inflammatory infiltration and myocyte damage in 11/12 rats using International Society For Heart and Lung Transplantation grading, compared to 0/12 rats with this grading in the ALLO + PBS group at 10 days post HT (p 0.001).Ultrasound-targeted galectin-7-siRNA knockdown with UTMD can prevent acute cellular rejection in the early period after allograft heart transplantation without the need for systemic immunosuppression.Microbubble, Acute Rejection, Heart Transplantation, Galectin-7, RNA.