Acoustic communication is important for the survival and reproduction of anurans and masking background noise is a critical factor for their effective acoustic communication. Males of the concave-eared frog (Odorrana tormota) have evolved an ultrasonic communication capacity to avoid masking by the widespread background noise of local fast-flowing streams, whereas females exhibit no ultrasonic sensitivity. However, the molecular mechanisms underlying the high-frequency hearing differences between the sexes of O. tormota are still poorly understood.In this study, we sequenced the brain transcriptomes of male and female O. tormota, and compared their differential gene expression. A total of 4,605 differentially expressed genes (DEGs) between the sexes of O. tormota were identified and eleven of them were related to auditory based on the annotation and enrichment analysis. Most of these DEGs in males showed a higher expression trend than females in both quantity and expression quantity. The highly expressed genes in males were relatively concentrated in neurogenesis, signal transduction, ion transport and energy metabolism, whereas the up-expressed genes in females were mainly related to the growth and development regulation of specific auditory cells.The transcriptome of male and female O. tormota has been sequenced and de novo assembled, which will provide gene reference for further genomic studies. In addition, this is the first research to reveal the molecular mechanisms of sex differences in ultrasonic hearing between the sexes of O. tormota and will provide new insights into the genetic basis of the auditory adaptation in amphibians during their transition from water to land.
Abstract Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC. In this study, data of patients with unresectable TC diagnosed from January 2017 were retrospectively collected from multiple centers. Treatment response, progression‐free survival (PFS), overall survival (OS), survival‐independent prognostic factor, and adverse events (AEs) were further analyzed. As a result, a total of 93 patients with unresectable TC were enrolled, of which 54 received first‐line chemotherapy, and 39 received chemotherapy plus immune checkpoint inhibitors (ICIs). The objective response rate was 50% (27/54) in the chemotherapy group and 76.9% (30/39) in the chemotherapy plus ICIs group. The chemotherapy plus ICIs group achieved significant median PFS benefit (8.8 vs. 34.9 months, p < .001) and median OS benefit (41.8 months vs. not reached, p = .025). Multivariate analysis showed that ICIs and local therapy were independent prognostic factors for PFS. In addition, 17 patients developed immune‐related AEs (IRAEs), of which 15 (38.5%) had Grade 1 or 2 IRAEs and 2 (5.1%) had Grade 3 IRAEs in the chemotherapy plus ICIs group. In conclusion, the efficacy of chemotherapy plus ICIs is superior to chemotherapy, and the adverse effects are manageable in patients with unresectable TC.
Abstract The ATP-adenosine pathway has emerged as a promising target for cancer therapy, but challenges remain in achieving effective tumor control. Early research focused on blocking the adenosine generating enzyme CD73 and the adenosine receptors A2AR or A2BR in cancer. However, recent studies have shown that targeting CD39, the rate-limiting ecto-enzyme of the ATP-adenosine pathway, can provide more profound anti-tumor efficacy by reducing immune-suppressive adenosine accumulation and increasing pro-inflammatory ATP levels. In addition, combining CD39 blocking antibody with PD-1 immune checkpoint therapy may have synergistic anti-tumor effects and improve patient survival. This review will discuss the immune components that respond to CD39 targeting in the tumor microenvironment. Targeting CD39 in cancer has been shown to not only decrease adenosine levels in the tumor microenvironment (TME), but also increase ATP levels. Additionally, targeting CD39 can limit the function of Treg cells, which are known to express high levels of CD39. With phase I clinical trials of CD39 targeting currently underway, further understanding and rational design of this approach for cancer therapy are expected.
Abstract Background : HITT inhibits colon cancer. This study explored its role in gastric cancer (GC). Methods : HITT, mature miR-602 and premature miR-602 expression in paired GC and normal tissues (62 patients) was studied by RT-qPCR. RNA pull-down assay was performed to analyze the direct interaction between HITT and mature miR-602. The subcellular location of HITT was analyzed by nuclear fractionation assay. The role of HITT in regulating miR-602 maturation was analyzed by overexpression assay. Cell apoptosis was analyzed by flow cytometry. Result : Our assays illustrated that HITT was highly expressed in GC and mature miR-602 was lowly expressed in GC. No alteration in premature miR-602 in GC was observed. HITT was located to both nucleus and cytoplasm, and it can directly interact with miR-602. HITT overexpression in GC cells increased the expression of mature miR-602 but not premature miR-602. HITT overexpression increased GC cell apoptosis and suppressed the role of miR-602 in inhibiting GC cell apoptosis. Conclusion : Therefore, HITT may promote GC cell apoptosis by suppressing the maturation of miR-602.
Abstract Few epidemiological studies have evaluated the effects of air pollution on the risk of pulmonary tuberculosis (TB). We investigated the associations of ambient air pollutants (particulate matter with aerodynamic diameter <2.5 μm (PM 2.5 ), sulfur dioxide (SO 2 ),nitrogen dioxide (NO 2 ), ozone (O 3 ), and carbon monoxide (CO)) in relation to the risk of pulmonary TB in a cohort of Chinese TB patient in Jinan city from 2011 to 2015. A total of 9344 newly diagnosed pulmonary TB cases were included. Poisson regression model was employed to estimate the risk of air pollution and daily diagnosed pulmonary TB. Four different air pollution exposure windows (3, 6, 9, and 12 months) before TB diagnoses were calculated from the daily concentration of air pollution. In overall analysis, we did not find strong evidence for an association between continuous exposures to most ambient air pollutants and risk for pulmonary TB. However, in categorical analysis, we observed statistically significant overall associations between pulmonary TB risk and PM 2.5 (3 month exposure window: RR = 1.228, 95%CI: 1.091–1.381) as well as CO (3 month exposure window: RR = 1.169, 95%CI: 1.028–1.329; 9 month exposure window: RR = 1.442, 95%CI: 1.028–2.024) exposures. Moreover, subgroup analyses suggested that most of the air pollutants (PM 2.5 , SO 2 , O 3 , and CO) were significantly associated with increased risk of TB among the males, the females, the <60 years, and the smear negative cases. The dominant statistically significant associations were detected at 3-month exposure window of air pollution before the diagnosis of TB. Our results detected positive associations between ambient PM 2.5 , CO exposures and the risk of newly diagnosed pulmonary TB in China. The suggestive evidence that the 3 month air pollution exposure window was associated with increased TB risk warrants further investigation.
Anaplastic thyroid carcinoma (ATC) is one of the most lethal carcinoma with a poor prognosis; however, molecular mechanisms underlying the aggressiveness of ATC remain unclear. Our goal was to examine the expression of X-linked inhibitor of apoptosis protein (XIAP) in ATC, as well as its role in ATC tumorigenesis. This is a retrospective study of ATC patients from the Second Affiliated Hospital of Harbin Medical University during June 2003 to October 2013. The expression of XIAP in tumor specimens of ATC patients was examined by immunohistochemical staining. The roles of XIAP in proliferation, migration, invasion, and chemoresistance were investigated by shRNA mediated-knockdown of XIAP in human ATC cell lines. The effect of XIAP on tumorigenesis was evaluated using a xenograft tumor model with nude mice. XIAP expression was significantly higher in the invasive area of ATC samples, whereas XIAP expression was negative in either normal thyroid follicular epithelial cells or the differentiated papillary thyroid carcinoma. XIAP-depleted ATC cells showed a remarkable decrease in the proliferation, migration, and invasion compared with the scramble group. Knockdown of XIAP expression significantly enhanced the chemosensitivity of WRO and SW1736 cells to docetaxel or taxane. Moreover, knockdown of XIAP significantly suppressed ATC tumorigenesis in vivo. XIAP is highly expressed in ATC cells and tumors. XIAP play important roles in tumor behaviors and chemosensitivity of ATC cells. XIAP may function in ATC aggressiveness and may serve as a potential therapeutic target for ATC treatment.
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