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Hypoxia-inducible factors (HIFs) play a key role in regulating cellular responses to low-oxygen conditions, particularly in promoting angiogenesis in tumor microenvironments. Aberrant HIF signaling enhances tumor growth and contributes to resistance against chemotherapy and radiotherapy. Targeting the HIF pathway has emerged as a promising strategy for cancer therapy. This study aimed to identify novel inhibitors of HIF signaling and evaluate their potential against the HIF–vascular endothelial growth factor (VEGF) axis for antiangiogenic therapy. In screening our in-house drug library using hypoxia response element dual-luciferase assay, HST3782, a novel 3-hydroxy-8-azabicyclo[3.2.1]octane-bridged compound, was identified as a promising HIF inhibitor, with IC50 of 1.028 μmol/L. In this work, the inhibitory effect of HST3782 on HIF signaling was confirmed in triple-negative breast cancer cells (SUM159) under hypoxic conditions (1% O2). Quantitative real-time polymerase chain reaction suggested the inhibitory effect of HST3782 on the expression of angiogenic genes, including VEGFa, VEGFR-1, BNIP3, and SERPINE1 in 786-O cells. Zebrafish model testing revealed that HST3782 inhibited intersegmental and subintestinal vessel development by up to 56% without marked toxicity. HST3782 was synthesized through a two-step 1,2,4 triazole cyclization reaction, followed by amide formation and ketone reduction steps. The last step of hydrogenation with sodium borohydride yielded a pair of endo-exo isomers. 2D-NOESY (Nuclear Overhauser effect spectroscopy) analysis confirmed that the compound's endo isomer (HST3782) had superior inhibitory effects relative to its exo form (8b). Given the above, HST3782 is a novel HIF inhibitor, with strong antiangiogenic effects and presents a valuable scaffold for future development of antiangiogenic drugs targeting the HIF–VEGF axis. Further studies are warranted to optimize HST3782's pharmacokinetics and therapeutic efficacy for antiangiogenic therapy in hypoxia-related malignancies.

In recent years, wireless sensor devices have become able to perform multiple functions such as detecting human sleep conditions, blood pressure, heartbeat, and running paths. We use the wireless channel model of a wearable Zigbee wireless sensing node to conduct research on human posture recognition. The received signal strength indicator (RSSI) obtained through the transmission and reception of wireless signals is used to obtain the model of the wireless channel. The wireless sensor nodes receive different RSSI patterns of human gesture based on which they recognize a gesture through their respective wireless channels by performing distance processing on the collected signal data. However, in this paper, we propose a weighted random reference pattern (WRRP) to achieve a higher recognition accuracy. Experimental results show that WRRP can achieve a recognition accuracy of 98%. [ABSTRACT FROM AUTHOR]

The urban–rural gap remains to be one fundamental inequality in modern China; however, the symbolic boundary derived from such socioeconomic inequality is less examined. Centre on two parallel initiatives aimed at cultural empowerment for rural China—independent bookstores and public-subsidized libraries—this study tries to explicate the multidimensional nature of boundaries and emphasize the cultural mechanism of boundary reproduction under institutional layering environment. We draw from policy trajectories, media discourse, and first-hand interviews in two villages, and reveal that despite the idealized portrayal of bookstores as a public cultural centre for empowerment, the symbolic construction wielded by cultural entrepreneurs is not sufficient in dissolving social differences in a digitalized society. Local villagers are not part of the "cultural consumption as identity building" ritual therefore being excluded from an urban-and-consumption culture-oriented space. Moreover, local villagers adopt differentiated interpretive strategies towards culture-led regeneration projects, so that "rural culture" is merely the swirl of an empty signal in Baudrillard's sense that does not bear the symbolic efficacy promoted by top-down initiatives. [ABSTRACT FROM AUTHOR]

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peridevice leak (PDL), post--LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post--LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28--10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post--LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. [ABSTRACT FROM AUTHOR]

This is the first investigation to report the processing and properties of ultrahigh molecular weight polyethylene (UHMWPE)/ functionalized activated nanocarbon (FANC) gel solutions with the aid of supercritical carbon dioxide (scC[O.sub.2]). The ultradrawing and ultimate tensile properties of scC[O.sub.2]UHMWPE and scC[O.sub.2]UHMWPE/FANC fibers were found to improve considerably compared to those of UHMWPE and UHMWPE/FANC fibers prepared in the conventional way. The maximum achievable draw ratio obtained for the optimal scC[O.sub.2]UHMWPE/FANC fibers drawn at 95 C reached 445. The highest tensile tenacity of the fully drawn scC[O.sub.2]UHMWPE/FANC fiber reached an extraordinary high value of 104 g/d, which is about 3.2 and 1.1 times of that of the optimal UHMWPE and UHMWPE/FANC fully drawn fibers, respectively. The [[sigma].sub.f] obtained for the optimally fully drawn scC[O.sub.2]UHMWPE/FANC fiber is about 25 times of those of steel fibers and is the highest tensile tenacity ever reported for single-stage drawn polymeric fibers. Considerably lower dynamic transition temperatures and evaluated thinner crystal lamellae nucleated off of extended chains or FANC nucleants were found for as-prepared scC[O.sub.2]UHMWPE and scC[O.sub.2]UHMWPE/FANC fibers compared with UHMWPE and UHMWPE/FANC fibers, respectively. Specific surface area, morphological, and Fourier transform infrared analyses of the activated nanocarbon (ANC), acid-treated activated nanocarbon (ATANC) and FANC nanofillers and investigation of thermal, morphological, and orientation factor properties of the as-prepared and drawn UHMWPE, UHMWPE/FANC, scC[O.sub.2]UHMWPE, and scC[O.sub.2]UHMWPE/FANC fibers were performed to understand the remarkable ultradrawing, dynamic transition, and ultimate tensile properties obtained for scC[O.sub.2]UHMWPE and scC[O.sub.2]UHMWPE/FANC fibers., INTRODUCTION Ultrahigh molecular weight polyethylene (UHMWPE) is not only one of three high performance fibers in the world today, but it is also known as the toughest fiber. UHMWPE fibers [...]