Insight of novel biomarkers for papillary thyroid carcinoma through multiomics

IntroductionThe overdiagnosing of papillary thyroid carcinoma (PTC) in China necessitates the development of an evidence-based diagnosis and prognosis strategy in line with precision medicine. A landscape of PTC in Chinese cohorts is needed to provide comprehensiveness.Methods6 paired PTC samples were employed for whole-exome sequencing, RNA sequencing, and data-dependent acquisition mass spectrum analysis. Weighted gene co-expression network analysis and protein-protein interactions networks were used to screen for hub genes. Moreover, we verified the hub genes' diagnostic and prognostic potential using online databases. Logistic regression was employed to construct a diagnostic model, and we evaluated its efficacy and specificity based on TCGA-THCA and GEO datasets.ResultsThe basic multiomics landscape of PTC among local patients were drawn. The similarities and differences were compared between the Chinese cohort and TCGA-THCA cohorts, including the identification of PNPLA5 as a driver gene in addition to BRAF mutation. Besides, we found 572 differentially expressed genes and 79 differentially expressed proteins. Through integrative analysis, we identified 17 hub genes for prognosis and diagnosis of PTC. Four of these genes, ABR, AHNAK2, GPX1, and TPO, were used to construct a diagnostic model with high accuracy, explicitly targeting PTC (AUC=0.969/0.959 in training/test sets).DiscussionMultiomics analysis of the Chinese cohort demonstrated significant distinctions compared to TCGA-THCA cohorts, highlighting the unique genetic characteristics of Chinese individuals with PTC. The novel biomarkers, holding potential for diagnosis and prognosis of PTC, were identified. Furthermore, these biomarkers provide a valuable tool for precise medicine, especially for immunotherapeutic or nanomedicine based cancer therapy

BRD4 promotes the migration and invasion of bladder cancer through the Sonic hedgehog signaling pathway and enhances cisplatin resistance

Platinum-based chemotherapy is a widely used strategy in bladder cancer (BCa) treatments. However, the clinical efficacy is affected by chemotherapy resistance with complex molecular mechanisms. Therefore, it is urgent to explore new targets for BCa therapy. Here, we showed that bromodomain-4 protein (BRD4) expression was obviously upregulated in BCa tissues and cells. Inhibition of BRD4 attenuated the migration and invasion of BCa cells, which was rescued by the Sonic hedgehog (SHH) pathway activator recombinant human Sonic hedgehog peptide (rhSHH). We further found that cisplatin (DDP) suppressed the migration and invasion of BCa cells in vitro and inhibited tumor growth in vivo; however overexpression of BRD4 weakened the pharmacological effects of DDP. In brief, our research reveals that BRD4 promotes migration and invasion by positively regulating the SHH pathway, drives DDP resistance in BCa and is a novel therapeutic target for the treatment of BCa.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Attenuation Effect of Recovery Sleep for Impaired Reproductive Function in Male Rats by Sleep Deprivation

Purpose: The aim of the present study was to test the hypothesis that recovery sleep could counteract the detrimental effects of sleep deprivation (SD) on male rats’ fertility. Materials and Methods: Twenty-two rats were housed in groups of six per cage with unrestricted access to food and water in a room. The modified multiple platform method was used to induce SD in rats over a 96-hour period. We examined the effect of SD on semen quality, reproductive hormones, and testicular histology in adult male rats. Then, we investigated the effect of 7 days recovery sleep on impaired reproductive function induced by SD. Results: After the acclimation period, 22 rats were randomly separated into three experimental groups (SD, recovery sleep, and the control groups). Ninety-six hours of SD resulted in a significant decrease in sperm motility (24.33±10.93 vs . 48.20±8.55, p<0.001) and the number of morphologically normal sperm (9.68±2.77 vs. 26.21±14.60, p<0.01) in rats, accompanied by a decrease in testosterone levels (1.53±0.55 vs. 4.44±0.56, p<0.001) and destruction of testicular tissue structure compared with control group. After 7 days of recovery sleep, semen quality, especially sperm motility, was improved and testosterone levels were significantly higher compared to post-SD (3.70±0.53 vs. 1.53±0.55, p<0.05), but remained low compared to the control group. Conclusions: In conclusion, 96 hours of SD deteriorated the parameters of sperm motility and the number of morphologically normal sperm in rats, probably due to the decrease in serum testosterone levels and the disruption of testicular tissue structure when compared to the control group. After 7 days of recovery sleep, semen parameter, especially sperm motility and testosterone levels did not return to baseline levels compared to the control group

CircHIPK3 negatively regulates autophagy by blocking VCP binding to the Beclin 1 complex in bladder cancer

Abstract Circular RNA HIPK3 (circHIPK3) mediates the progression of multiple cancers, including bladder cancer, by regulating cell migration, autophagy and epithelial mesenchymal transition. However, the mechanism by which circHIPK3 regulates autophagy in bladder cancer cells remains unclear. Autophagy is a common self-protection mechanism in eukaryotic cells and is essential for cell survival and death regulation. However, it is unclear whether circHIPK3 affects the level of autophagy in bladder cancer through binding proteins, and the potential regulatory mechanism is unknown. Here, we found that circHIPK3 levels were significantly lower and autophagy-related proteins were significantly upregulated in bladder cancer cells and tissues compared to normal controls. CircHIPK3 downregulation promoted bladder cancer cell proliferation, while circHIPK3 overexpression inhibited proliferation. CircHIPK3 overexpression significantly suppressed autophagy in bladder cancer cells. Overexpression of circHIPK3 did not affect VCP protein expression but inhibited the VCP/Beclin 1 interaction. VCP also stabilized Beclin 1 and promoted autophagy in bladder cancer cells by downregulating ataxin-3. Thus, circHIPK3 may play an important role in bladder cancer by inhibiting VCP-mediated autophagy

Estimations of evapotranspiration in an age sequence of Eucalyptus plantations in subtropical China.

Eucalyptus species are widely planted for reforestation in subtropical China. However, the effects of Eucalyptus plantations on the regional water use remain poorly understood. In an age sequence of 2-, 4- and 6-year-old Eucalyptus plantations, the tree water use and soil evaporation were examined by linking model estimations and field observations. Results showed that annual evapotranspiration of each age sequence Eucalyptus plantations was 876.7, 944.1 and 1000.7 mm, respectively, accounting for 49.81%, 53.64% and 56.86% of the annual rainfall. In addition, annual soil evaporations of 2-, 4- and 6-year-old were 318.6, 336.1, and 248.7 mm of the respective Eucalyptus plantations. Our results demonstrated that Eucalyptus plantations would potentially reduce water availability due to high evapotranspiration in subtropical regions. Sustainable management strategies should be implemented to reduce water consumption in Eucalyptus plantations in the context of future climate change scenarios such as drought and warming

Data from: Estimations of evapotranspiration in an age sequence of Eucalyptus plantations in subtropical China

Eucalyptus species are widely planted for reforestation in subtropical China. However, the effects of Eucalyptus plantations on the regional water use remain poorly understood. In an age sequence of 2-, 4- and 6-year-old Eucalyptus plantations, the tree water use and soil evaporation were examined by linking model estimations and field observations. Results showed that annual evapotranspiration of each age sequence Eucalyptus plantations was 876.7, 944.1 and 1000.7 mm, respectively, accounting for 49.81%, 53.64% and 56.86% of the annual rainfall. In addition, annual soil evaporations of 2-, 4- and 6-year-old were 318.6, 336.1, and 248.7 mm of the respective Eucalyptus plantations. Our results demonstrated that Eucalyptus plantations would potentially reduce water availability due to high evapotranspiration in subtropical regions. Sustainable management strategies should be implemented to reduce water consumption in Eucalyptus plantations in the context of future climate change scenarios such as drought and warming

Tim-3 regulates the immunosuppressive function of decidual MDSCs via the Fyn-STAT3-C/EBPβ pathway during Toxoplasma gondii infection.

Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by Toxoplasma gondii infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during T. gondii infection. The expression of Tim-3 in decidual MDSCs was significantly downregulated following T. gondii infection. The proportion of monocytic MDSCs population, the inhibitory effect of MDSCs on T-cell proliferation, the levels of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs were all decreased in T. gondii-infected pregnant Tim-3 gene knockout (Tim-3KO) mice compared with infected pregnant WT mice. After treatment with Tim-3-neutralizing Ab in vitro, the expression levels of Arg-1, IL-10, C/EBPβ, and p-STAT3 were decreased, the interaction between Fyn and Tim-3 or between Fyn and STAT3 was weakened, and the binding ability of C/EBPβ to the promoters of ARG1 and IL10 was decreased in human decidual MDSCs with T. gondii infection, while opposite results were observed following treatment with galectin-9 (a ligand for Tim-3). Inhibitors of Fyn and STAT3 also downregulated the expression of Arg-1 and IL-10 in decidual MDSCs and exacerbated adverse pregnancy outcomes caused by T. gondii infection in mice. Therefore, our studies discovered that the decrease of Tim-3 after T. gondii infection could downregulate the functional molecules of Arg-1 and IL-10 expression in decidual MDSCs through the Fyn-STAT3-C/EBPβ signaling pathway and weaken their immunosuppressive function, which eventually contribute to the development of adverse pregnancy outcomes

Vegetation cover-another dominant factor in determining global water resources in forested regions

Forested catchments provide critically important water resources. Due to dramatic global forest change over the past decades, the importance of including forest or vegetation change in the assessment of water resources under climate change has been highly recognized by Intergovernmental Panelon Climate Change (IPCC); however, this importance has not yet been examined quantitatively across the globe. Here, we used four remote sensing-based indices to represent changes in vegetation cover in forest-dominated regions, and then applied them to widely used models: the Fuh model and the Choudhury-Yang model to assess relative contributions of vegetation and climate change to annual runoff variations from 2000 to 2011 in forested landscape (forest coverage &gt;30%) across the globe. Our simulations show that the global average variation in annual runoff due to change in vegetation cover is 30.7% +/- 22.5% with the rest attributed to climate change. Large annual runoff variation in response to vegetation change is found in tropical and boreal forests due to greater forest losses. Our simulations also demonstrate both offsetting and additive effects of vegetation cover and climate in determining water resource change. We conclude that vegetation cover change must be included in any global models for assessing global water resource change under climate change in forest-dominant areas

Monthly changes of soil evaporation in different Eucalyptus plantations (the error bar represents the SD).

<p>Monthly changes of soil evaporation in different Eucalyptus plantations (the error bar represents the SD).</p