Nephrolithiasis is a common disease affecting almost all populations, with an increasing prevalence over the past decades. Previous studies revealed several functional polymorphisms associated with ...the pathogenesis of nephrolithiasis. However, data on Asian populations are limited. In this study, three candidate polymorphisms were selected from previous studies to investigate the correlations with nephrolithiasis in a Taiwanese population. In total, 454 nephrolithiasis patients were recruited from Kaohsiung Medical University Hospital, with SNP frequency for 1513 subjects of general population from the Taiwan Biobank (TWB) as a genotypic reference. Results revealed that subjects with minor TT genotype at rs1256328 (alkaline phosphatase, liver/bone/kidney (ALPL)) have higher susceptibility to nephrolithiasis (odds ratio (OR) = 2.03, p = 0.0013). In addition, subjects carrying the minor AA genotype at rs12654812 (regulator of G protein signaling 14 (RGS14)) have higher susceptibility to nephrolithiasis (OR = 1.91, p = 0.0017). Among nephrolithiasis patients, subjects with GG at rs7627468 (calcium-sensing receptor (CASR)) have lower pH level in urine (p = 0.0088). Importantly, rs7627468 is associated with the expressions of IQCB1 and EAF2. rs12654812 could influence the expression of RGS14 itself, MXD3, and FGFR4. In summary, this study successfully validated the genetic roles of rs1256328 and rs12654812 in human nephrolithiasis.
Economic agglomeration is an important driving force for China's economic growth and the transformation of its industrial structure. However, whether economic agglomeration is accompanied by haze ...pollution is a major concern for environmental managers and policymakers. As one of the most significant ecological barriers and major economic zones, China's Yellow River basin faces severe air pollution. Hence, taking energy consumption as an input factor and haze pollution as an undesirable output in an output density model, this study investigates, both theoretically and empirically, the transmission mechanisms among economic agglomeration, labor productivity, and haze pollution. We construct a spatial Durbin model to verify the explanatory power of our theoretical model based on panel data for 74 cities in China's Yellow River basin during 2005–2016. Economic agglomeration's effect on haze pollution is further tested using a mediating effect model and the instrumental variable method. The results show that there is an N-shaped relationship between economic agglomeration and haze pollution and a U-shaped relationship between labor productivity and haze pollution. Labor productivity is an important mediator in economic agglomeration's effect on haze pollution. Haze pollution not only has path dependence in the time dimension but also has a significant spillover effect in the spatial dimension. Therefore, we propose actively cultivating urban agglomeration in the Yellow River basin, enhancing the degree of economic agglomeration, and improving regional haze pollution prevention and control mechanisms.
•Whether economic agglomeration affects haze pollution is investigated.•A spatial Durbin model is applied using data from 74 cities along the Yellow River basin.•Economic agglomeration affects haze pollution via the mediator of labor productivity.•The relationships among economic agglomeration, labor productivity, and haze pollution are verified.
Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. BAY 11–7085 (BAY), which is a well-known IκBα inhibitor, suppressed viability in cancer ...cells via induction of ferroptotic death in an NF-κB-independent manner. Reactive oxygen species scavenging, relief of lipid peroxidation, replenishment of glutathione and thiol-containing agents, as well as iron chelation, rescued BAY-induced cell death. BAY upregulated a variety of Nrf2 target genes related to redox regulation, particularly heme oxygenase-1 (HO-1). Studies with specific inhibitors and shRNA interventions suggested that the hierarchy of induction is Nrf2−SLC7A11−HO-1. SLC7A11 inhibition by erastin, sulfasalazine, or shRNA interference sensitizes BAY-induced cell death. Overexperession of SLC7A11 attenuated BAY-inhibited cell viability. The ferroptotic process induced by hHO-1 overexpression further indicated that HO-1 is a key mediator of BAY-induced ferroptosis that operates through cellular redox regulation and iron accumulation. BAY causes compartmentalization of HO-1 into the nucleus and mitochondrion, and followed mitochondrial dysfunctions, leading to lysosome targeting for mitophagy. In this study, we first discovered that BAY induced ferroptosis via Nrf2−SLC7A11−HO-1 pathway and HO-1 is a key mediator by responding to the cellular redox status.
•BAY 11–7085 induces ferroptotic cell death regardless of IκBα−NF-κB signaling.•BAY 11–7085 triggers ferroptosis through a Nrf2−SLC7A11−HO-1 signaling pathway.•HO-1 mediates redox regulation of ferroptotic death.•HO-1 causes endoplasmic reticulum stress and mitophagy.
Municipal solid waste incineration (MSWI) bottom ash has gained increasing attentions for its friendly application worldwide, due to promotion of waste recycling. One of the biggest concerns for ...incineration bottom ash (IBA) utilization lies in its elevated metal concentrations and leaching potential. While challenges faced by the user are miscellaneous based on several aspects—regulations and rules, the heterogeneity of IBA sources, specific risks arisen from individual applications and/or mixed public views, etc. Extensive knowledge on IBA characterization, existing treatment and application contributes to optimize life cycle of the bottom ash, herein enhancing the IBA management practices. On the understanding that both feedstock and the process for incineration are various, properties, treatments and applications of the IBA are accordingly different. Nevertheless, literature reviewed data indicate evidently that IBA, varying in its original resources and treatment facilities though, shares common geotechnical and chemical properties. As the technology development on the IBA is dominated by these common properties, through which the proper treatment and application could be well determined. In this review three perspectives were concentrated. First, general properties of IBA e.g. heavy metals and their leaching potential, bulk components, particle size distribution and pH were investigated, whereby the general trends were indicated with collective plots. Secondly, the existing status quo on IBA treatment methods and applications were investigated, suggesting a highest potential as low-strength aggregates. Thirdly, toxicity studies and LCA on IBA as emerging research topics were also investigated, to further justify its application feasibility.
A reduction of the bandgap and an enhancement of the charge transport properties of a LBG polymer (PBDTT‐DPP) can be achieved simultaneously by changing the sulfur atoms on the DPP unit to selenium ...atoms. The newly designed polymer, PBDTT‐SeDPP (Eg = 1.38 eV), shows excellent photovoltaic performance in single junction devices with power conversion efficiencies (PCEs) over 7% and photo‐response up to 900 nm. A tandem polymer solar cell and a visibly transparent solar cell based on PBDTT‐SeDPP show 9.5% and 4.5% PCEs, which are superior to those based on PBDTT‐DPP.
Architecture of the type IVa pilus machine Chang, Yi-Wei; Rettberg, Lee A.; Treuner-Lange, Anke ...
Science (American Association for the Advancement of Science),
03/2016, Letnik:
351, Številka:
6278
Journal Article
Recenzirano
Odprti dostop
Type IVa pili are filamentous cell surface structures observed in many bacteria. They pull cells forward by extending, adhering to surfaces, and then retracting. We used cryo-electron tomography of ...intact Myxococcus xanthus cells to visualize type IVa pili and the protein machine that assembles and retracts them (the type IVa pilus machine, or T4PM) in situ, in both the piliated and nonpiliated states, at a resolution of 3 to 4 nanometers. We found that T4PM comprises an outer membrane pore, four interconnected ring structures in the periplasm and cytoplasm, a cytoplasmic disc and dome, and a periplasmic stem. By systematically imaging mutants lacking defined T4PM proteins or with individual proteins fused to tags, we mapped the locations of all 10 T4PM core components and the minor pilins, thereby providing insights into pilus assembly, structure, and function.
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis ...factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.
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•TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation•Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization•CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination•Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy
Lim et al. show that inflammation increases PD-L1 expression in tumors through TNF-α-mediated activation of NF-κB, leading to transactivation of CSN5. CSN5 reduces PD-L1 ubiquitination and stabilizes it. Inhibition of CSN5 cooperates with anti-CTLA4 to enhance anti-tumor T cell function and reduce tumor growth.
•Propose the first BAT-based Monte Carlo simulation (BAT-MCS).•The simulation number in BAT-MCS is self-adaptive intelligently.•BAT-MCS uses the super vectors to reduce the runtime and space.•BAT-MCS ...is more efficient than the traditional MCS.•BAT-MCS is suitable for large-scale network reliability problems.
The Monte Carlo simulation method (MCS) is a computational algorithm and statistical methodology for the problems that are too complex to solve analytically. The computational cost and total runtime of the MCS can be quite high as it requires many samples to obtain an accurate approximation with low variance. In this paper, a novel self-adaptive MCS, called BAT-MCS, is proposed to reduce the runtime and variance based on the binary-adaption-tree algorithm (BAT) and the self-adaptive simulation number. The time complexity and simulation number of the BAT-MCS are discussed with the expectation and variance of obtained estimators. The performance of the proposed BAT-MCS is compared to that of the traditional MCS extensively on a large-scale network reliability problem.
Massive open online courses (MOOCs) have developed rapidly and become tremendously popular because of their plentiful gamification designs, such as reputation points, rewards, and goal setting. ...Although previous studies have mentioned a broad range of gamification designs that might influence MOOC learner engagement, most gamified MOOCs fail to meet learning objectives because of a lack of research regarding suitable game design, as well as poor rationale for or design of gamification mechanics. This study aims to explore and identify engaging gamification mechanics for MOOC learners. We conducted a focus group interview with 25 MOOC frequent users to identify 40 gamification mechanics. This study then determined the relative engagingness of these gamification mechanics by administering an online survey to 5,020 MOOC learners. The results indicated that the 10 most engaging gamification mechanics accounted for more than 50% of the engagingness. The mechanics of the Where's Wally game is extremely engaging for MOOC learners; however, they it is not been demonstrated in previous relevant studies. Finally, we discuss the top five engaging gamification mechanics and their implications.
Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation ...potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.
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