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Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1 -/- zebrafish ( Danio rerio ) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1 -/- fish compared to cyp17a1 +/+ male fish, including stearoyl-CoA desaturase ( scd ) and fatty acid synthase ( fasn ). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1 +/+ male fish but not in cyp17a1 -/- fish. Both androgen receptor ( ar )-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca ), fasn , and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1 -/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

Cancer is a genetic disease caused by alterations in genome and epigenome and is one of the leading causes for death worldwide. The exploration of disease development and therapeutic strategies at the genetic level have become the key to the treatment of cancer and other genetic diseases. The functional analysis of genes and mutations has been slow and laborious. Therefore, there is an urgent need for alternative approaches to improve the current status of cancer research. Gene editing technologies provide technical support for efficient gene disruption and modification in vivo and in vitro, in particular the use of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. Currently, the applications of CRISPR-Cas systems in cancer rely on different Cas effector proteins and the design of guide RNAs. Furthermore, effective vector delivery must be met for the CRISPR-Cas systems to enter human clinical trials. In this review article, we describe the mechanism of the CRISPR-Cas systems and highlight the applications of class II Cas effector proteins. We also propose a synthetic biology approach to modify the CRISPR-Cas systems, and summarize various delivery approaches facilitating the clinical application of the CRISPR-Cas systems. By modifying the CRISPR-Cas system and optimizing its in vivo delivery, promising and effective treatments for cancers using the CRISPR-Cas system are emerging., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Oral squamous cell carcinoma (OSCC), the eighth most prevalent cancer in the world, arises from the interaction of multiple factors including tobacco, alcohol consumption, and betel quid. Chemotherapeutic agents such as cisplatin, 5-fluorouracil, and paclitaxel have now become the first-line options for OSCC patients. Nevertheless, most OSCC patients eventually acquire drug resistance, leading to poor prognosis. With the discovery and identification of non-coding RNAs (ncRNAs), the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized. The mechanisms of drug resistance of OSCC are intricate and involve drug efflux, epithelial-mesenchymal transition, DNA damage repair, and autophagy. At present, strategies to explore the reversal of drug resistance of OSCC need to be urgently developed. Nano-delivery and self-cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting, controlled release, and consistent pharmacokinetic profiles. In particular, the combined application of new technologies (including CRISPR systems) opened up new horizons for the treatment of drug resistance of OSCC. Hence, this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC, elucidated multiple ncRNA-meditated mechanisms of drug resistance of OSCC, and discussed the potential value of drug delivery platforms using nanoparticles and self-cells as carriers in drug resistance of OSCC., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

At present, emerging evidence shows that non-coding RNAs (ncRNAs) play crucial roles for development of multiple tumors. Amongst these ncRNAs, long non-coding RNAs (lncRNAs) play prominent roles in physiological and pathological processes. LncRNAs are RNA transcripts larger than 200 nucleotides and have been shown to serve important regulatory roles in different types of cancer via interactions with DNA, RNA and proteins. Head and neck squamous cell carcinoma (HNSCC) is one of the most malignant tumors with low survival rates in advanced stages. Recently, lncRNAs have been demonstrated to be involved in a wide range of biological processes, including proliferation, metastasis, and prognosis of HNSCC. Therefore, this review describes molecular mechanisms of up- or down-regulation of lncRNAs and expounds their functions in pathology and clinical practices in HNSCC. It also highlights their potential clinical applications as biomarkers for the diagnosis, prognosis, and treatment of HNSCC. However, studies on lncRNAs are still not comprehensive, and more investigations are needed in the future., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of 2019 novel coronavirus disease (COVID-19), is currently spreading around the world. The WHO declared on January 31 that the outbreak of SARS-CoV-2 was a public health emergency. SARS-Cov-2 is a member of highly pathogenic coronavirus group that also consists of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Although respiratory tract lesions were regarded as main manifestation of SARS-Cov-2 infection, gastrointestinal lesions were also reported. Similarly, patients with SARS-CoV and MERS-CoV were also observed. Common gastrointestinal symptoms of patients mainly included diarrhea, vomiting and abdominal pain. Gastrointestinal lesions could be used as basis for early diagnosis of patients, and at the same time, controlling gastrointestinal lesions better facilitated to cut off the route of fecal-oral transmission. Hence, this review summarizes the characteristics and mechanism of gastrointestinal lesions caused by three highly pathogenic human coronavirus infections including SARS-CoV, MERS-CoV, as well as SARS-CoV-2. Furthermore, it is expected to gain experience from gastrointestinal lesions caused by SARS-CoV and MERS-CoV infections in order to be able to better relieve SARS-CoV-2 epidemic. Targetin gut microbiota to regulate the process of SARS-CoV-2 infection should be a concern. Especially, the application of nanotechnology may provide help for further controlling COVID-19., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To explore the associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid (GC) efficacy, anxiety, depression, and health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE) patients., Methods: All subjects were collected from the First and the Second Affiliated Hospital of Anhui Medical University in Hefei, China, during 2011 to 2015. In the case-control study, 541 SLE patients and 543 controls were recruited. In the follow-up study, 466 patients completed the 12-week follow-up and then were divided into GC-sensitive and GC-insensitive groups. Genotyping was determined using Multiplex SNaPshot technique. Data were analyzed using chi-square test and univariate and multivariate logistic regression analyses., Results: rs4713904, rs9368878, and rs7757037 of FKBP5 were associated with depression in SLE patients (rs4713904, P BH  = 0.037; rs9368878, P BH  = 0.001; rs7757037, P BH  = 0.003). Moreover, rs4713904 was associated with GC efficacy in males with SLE (P BH  = 0.011). The rs755658 of FKBP5 was associated with improvement in social function (P BH  = 0.022) and mental component summary (P BH  = 0.028). The rs4713907 of FKBP5 was related to improvement in total score of SF-36, bodily pain, and mental component summary score (all P BH  = 0.018). Furthermore, the rs12582595 of FKBP4 was correlated with general health improvement (P BH  = 0.033). No associations were seen between FKBP4/FKBP5 gene polymorphisms and SLE susceptibility and anxiety., Conclusions: FKBP5 gene polymorphisms may be associated with depression and GC efficacy of SLE patients. Meanwhile, the genetic polymorphisms of FKBP4 and FKBP5 genes may be associated with HRQOL improvement in SLE patients. Key Points • FKBP5 gene polymorphisms were associated with depression of SLE patients. • FKBP5 gene polymorphisms were associated with GC efficacy of SLE patients. • FKBP5 gene polymorphisms were associated with HRQOL improvement in SLE patients. • FKBP4 gene polymorphisms were associated with HRQOL improvement in SLE patients.

Objectives: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life., Methods: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction., Results: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms., Conclusions: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

Objectives: This study sought to examine the variation trends and seasonality of losing weight by using the data from Google Trends tool., Methods: According to the search term of [lose weight+weight loss], Google Trends data were obtained. Search activity was conducted within the USA, the UK, Canada, Ireland, Australia, and New Zealand from January 01, 2004, to December 31, 2018, utilizing the health category., Results: Dynamic series analysis and the plot of seasonal decomposition of time series show that relative search volume of [lose weight+weight loss] increased from 2004 to 2018 at both national and hemispherical levels. Statistically significant seasonal variations in relative search volume for the term [lose weight+weight loss] were observed using cosinor analyses in the USA (p<0.001), the UK (p<0.001), Canada (p<0.001), Ireland (p<0.001), Australia (p<0.001), and New Zealand (p<0.001), peaking in the spring months and reaching the lowest level in the autumn months. The highest level in spring and the lowest level in autumn were reversed by 6 months in both hemisphere countries, consistent with a seasonal pattern., Conclusion: Our results indicate that Internet search queries for losing weight increased within the timeframe of 2004 to 2018, likely reflecting the rising global public interest. In addition, the present research provided preliminary evidence that there is a seasonality of losing weight with a peak in the spring months., (Copyright © 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

MicroRNAs (miRNAs) are noncoding RNAs which control gene expression by the suppression of translation or the degradation of mRNAs. Dre-miR-21 (miR-21) has been reported to impact cardiac valvulogenesis in zebrafish embryos. However, the target genes of miR-21 are still largely unknown. Here a tandem isobaric mass tag (TMT)-based quantitative proteomic strategy was employed to identify the global profile of miR-21-regulated proteins. A total of 251 proteins were dysregulated after miR-21 knockdown, suggesting that they may be regulated by miR-21. Bioinformatics analysis indicated that these differentially expressed proteins (DEPs) participate in various biological processes, suggesting that miR-21 may be involved in diverse cellular pathways. Sixteen DEPs were also predicted to be miR-21 targets by at least two algorithms, and several candidate target genes were selected for further luciferase reporter analysis. The results showed that genes encoding tropomyosin 1 (tpm1) and poly(rC) binding protein 2 (pcbp2) are direct miR-21 targets. Taken together, our results not only reveal a large number of novel miR-21 regulated proteins that possess pleiotropic functions, but also provide novel insights into the molecular mechanisms of miR-21 regulation of zebrafish cardiac valvulogenesis and embryonic development.

Two daughters in a Chinese consanguineous family were diagnosed as diffuse pulmonary arteriovenous malformations (PAVMs) and screened using whole exome sequencing (WES) and copy number variations (CNVs) chips. Though no mutation was found in the established causative genes of capillary malformation-AVMs (CM-AVMs) or PAVMs, Ser161Ile (hg19 NM&#95;022493 c.482G>T) mutation in nuclear prelamin A recognition factor-like (NARFL) was identified. Ser161Ile mutation in NARFL conservation region was predicted to be deleterious and absent in 500 population controls and Exome Aggregation Consortium (ExAC) Database. And there was a dosage effect of the mutation on mRNA levels among family members and population controls, consistent with the instability of mutant mRNA in vitro. Accordingly, in lung tissue of the proband, NARFL protein expression was reduced but Fe3+ was overloaded with vascular endothelial growth factor (VEGF) overexpression. Furthermore, NARFL-knockdown cell lines demonstrated decreased activity of cytosolic aconitase, while NARFL-knockout zebrafish presented ectopic subintestinal vessels sprouts and upregulated VEGF. So we concluded that the Ser161Ile mutant induced NARFL deficiency and eventually diffuse PAVMs probably through VEGF pathway. In a word, we detected a functional mutation in NARFL, which might be the pathogenic gene in this pedigree.

Aim: To determine the basic demographic features of colorectal cancer (CRC) in five hospitals located in four different areas of Guangdong Province, China., Methods: A review of patient records from 1986 to 2006 from five hospitals was conducted. Patient data was obtained, including age, gender, location of lesions, staging and histological type of CRC. The Chi-square test was used to assess differences in rates and a significance level of 0.05 was used. Univariate comparisons were made via Fisher's exact tests., Results: Analysis was carried out on 8172 CRC patents, 6.1% (499/8172) of the patients were aged < or = 30 years. The peak incidence was between the ages 61-70 years (27.8%). The mean age at CRC diagnosis increased from 52 years (1986-1988) to 60 years (2004-2006) and the proportion of young CRC patients decreased from 8.0% to 5.9% over the same period. Of 8172 lesions, 4434 (54.3%) were located in rectum and 3738 (45.7%) in colon. The incidence of rectal cancer decreased significantly from 59.4% (1989-1991) to 51.8% (2004-2006) and right sided colon cancer increased from 40.6% to 48.2%. The mean age, anatomic distribution, histological type and differentiation degree were significantly different among the four geographical areas (P < 0.05)., Conclusion: The hospitalization rate for CRC has increased in Guangdong in recent years. The characteristics of CRC from the five hospitals located in the four different areas of Guangdong Province are also different. Further studies are needed to assess more recent trend in the incidence and prevalence of CRC as well as the respective roles of genetic and environmental factors in CRC.

Objectives: There are currently around 120 million rural-urban migrants in China. Elsewhere migration has been associated with increased vulnerability to mental health problems. This study was conducted to explore the mental health status and help seeking behaviours of migrant workers in Hangzhou city, Zhejiang Province, and to compare them with permanent urban and rural dwellers., Methods: A self-completion questionnaire including items relating to sociodemographics, health and lifestyles and mental health, was completed by 4453 migrant workers and 1957 urban workers in Hangzhou city, and by 1909 rural residents in Western Zhejiang Province., Results: The mean age of the migrants was 27 years, (male 29 years, female 25 years). They worked long hours (28% >12 h per day, 81% 6 or 7 days per week) and their living conditions were very basic. On the SF-36 mental health scale migrants had lower scores (52.4) than rural residents (60.4, P < 0.0001) but scored higher than urban residents (47.2, P = 0.003). The difference between urbanites and migrants disappeared after adjustment for confounders (P = 0.06). Independent predictors of better mental health status among migrants were being unmarried, migrating with a partner, higher salary, good self-reported health and good relationships with co-workers. There were small significant differences in suicide ideation and attempts between the three groups with suicide ideation commonest in migrants and suicide attempts most common in the rural population. Fewer than 1% across all three groups had received any professional help for depression or anxiety., Conclusion: Rural-urban migrant workers in this part of China are not especially vulnerable to poor mental health. This may result from a sense of well being associated with upward economic mobility and improved opportunities, and the relatively high social capital in migrant communities.