Apoptosis induced by endoplasmic reticulum (ER) stress plays a crucial role in mediating brain damage after ischemic stroke. Recently, Hes1 (hairy and enhancer of split 1) has been implicated in the regulation of ER stress, but whether it plays a functional role after ischemic stroke and the underlying mechanism remain unclear. In this study, using a mouse model of ischemic stroke via transient middle cerebral artery occlusion (tMCAO), we found that Hes1 was induced following brain injury, and that siRNA-mediated knockdown of Hes1 increased the cerebral infarction and worsened the neurological outcome, suggesting that Hes1 knockdown exacerbates ischemic stroke. In addition, mechanistically, Hes1 knockdown promoted apoptosis and activated the PERK/eIF2a/ATF4/ CHOP signaling pathway after tMCAO. These results suggest that Hes1 knockdown promotes ER stress-induced apoptosis. Furthermore, inhibition of PERK with the specific inhibitor GSK2606414 markedly attenuated the Hes1 knockdown-induced apoptosis and the increased cerebral infarction as well as the worsened neurological outcome following tMCAO, implying that the protection of Hes1 against ischemic stroke is associated with the amelioration of ER stress via modulating the PERK/ eIF2a/ATF4/CHOP signaling pathway. Taken together, these results unveil the detrimental role of Hes1 knockdown after ischemic stroke and further relate it to the regulation of ER stress-induced apoptosis, thus highlighting the importance of targeting ER stress in the treatment of ischemic stroke.

Abstract-Low-duty-cycle radio operations have been proposed for wireless networks facing severe energy constraints. Despite energy savings, duty-cycling the radio creates transient-available wireless links, making communication rendezvous a challenging task under the practical issue of clock drift. To overcome limitations of prior work, this paper presents PSR, a practical design for synchronous rendezvous in low-duty-cycle wireless networks. The key idea behind PSR is to extract timing information naturally embedded in the pattern of radio duty-cycling, so that normal traffic in the network can be utilized as a "free" input for drift detection, which helps reduce (or even eliminate) the overhead of traditional time-stamp exchange with dedicated packets or bits. To prevent an overuse of such free information, leading to energy waste, an energy-driven adaptive mechanism is developed for clock calibration to balance between energy efficiency and rendezvous accuracy. PSR is evaluated with both test-bed experiments and extensive simulations, by augmenting and comparing with four different MAC protocols. Results show that PSR is practical and effective under different levels of traffic load, and can be fused with those MAC protocols to improve their energy efficiency without major change of the original designs. I. INTRODUCTIONIn wireless networks with severe energy constraints, e.g., wireless sensor networks [1], low-duty-cycle radio operations have been proposed as one of the major techniques to elongate the network lifetime [5], since the radio can be a main source of energy consumption [13]. Basically, the RF module of a node stays active only for a small percentage of time during each duty-cycle period (e.g., 1%), while keeps in low-energy sleep/off mode for the rest of the time [5][28]. Low-duty-cycle radio activity has been favorable in applications such as environment monitoring (e.g., Redwood [3], GreenOrbs [9]), animal observation (e.g., Great Duck Island [10]), civil structure surveillance (e.g., Mine [11]), etc. In all those applications, low-duty-cycle networking provides a nice trade-off between service quality and energy cost; however, it also brings about transient-available radio links that are essentially at odd with highly efficient communication. This is because in low-dutycycle networks, two nodes located within each other's radio range can communicate only when both of them are active simultaneously for transmitting (TX) and receiving (RX) [12]. A problem called communication rendezvous [17].Many smart ideas have been proposed for the rendezvous task in low-duty-cycle wireless networks. They usually function at the MAC layer and can be categorized into two general classes: (i) asynchronous [5]

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The tumor microenvironment (TME) contributes to the initiation and progression of many neoplasms. However, the impact of low-grade glioma (LGG) purity on carcinogenesis remains to be elucidated. We selected 509 LGG patients with available genomic and clinical information from the TCGA database. The percentage of tumor infiltrating immune cells and the tumor purity of LGG were evaluated using the ESTIMATE and CIBERSORT algorithms. Stromal-related genes were screened through Cox regression, and protein-protein interaction analyses and survival-related genes were selected in 487 LGG patients from GEO database. Hub genes involved in LGG purity were then identified and functionally annotated using bioinformatics analyses. Prognostic implications were validated in 100 patients from an Asian real-world cohort. Elevated tumor purity burden, immune scores, and stromal scores were significantly associated with poor outcomes and increased grade in LGG patients from the TCGA cohort. In addition, CD3E was selected with the most significant prognostic value (Hazard Ratio=1.552, P<0.001). Differentially expressed genes screened according to CD3E expression were mainly involved in stromal related activities. Additionally, significantly increased CD3E expression was found in 100 LGG samples from the validation cohort compared with adjacent normal brain tissues. High CD3E expression could serve as an independent prognostic indicator for survival of LGG patients and promotes malignant cellular biological behaviors of LGG. In conclusion, tumor purity has a considerable impact on the clinical, genomic, and biological status of LGG. CD3E, the gene for novel membrane immune biomarker deeply affecting tumor purity, may help to evaluate the prognosis and develop individual immunotherapy strategies for LGG patients. Evaluating the ratio of differential tumor purity and CD3E expression levels may provide novel insights into the complex structure of the LGG microenvironment and targeted drug development.

Glioblastoma has been identified as the most common and aggressive primary brain tumor in adults. Recently, it has been found that cisplatin (DDP) treatment is a common chemotherapeutic method for GBM patients. circ_PTN (ID number: hsa_circ_0003949) is a newly found circular (circRNA) which has been proved to be highly expressed in GBM cells, while its role in GBM remains unclear. Therefore, our study focused on investigating the role of circ_PTN in the DDP resistance of GBM cells. The expression of circ_PTN in DDP-sensitive and DDP-resistant GBM cells was detected in our assay. Functional experiments were utilized to unveil the effects of circ_PTN on the DDP resistance of GBM cells. Moreover, mechanism assays were conducted to confirm the mechanism of how circ_PTN affected the DDP resistance of GBM cells. According to the results, we found that circ_PTN promoted the DDP resistance of GBM cells through activation of the PI3K/AKT pathway. Moreover, circ_PTN silencing inhibited the DDP resistance of GBM tumors in vivo . To conclude, our study unveiled the influence of circ_PTN on the DDP resistance of GBM cells, which might provide a therapeutic target for GBM treatment via DDP.

These findings suggest that the IL-16 rs 11556218 polymorphism may be used as a susceptibility marker for glioma.

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The base-induced formal [4+3] annulation reaction of in situ-formed aza-o-quinone methides and pyridinium 1,4-zwitterionic thiolates is reported. This protocol provides a novel and reliable method for the synthesis of biologically interesting benzo­[e]­[1,4]­thiazepine derivatives in synthetically useful yields. In addition, postsynthetic modification results in the formation of its sulfoxide and sulfone derivatives.