Up till now, studies have not been conducted on how the combination of Quercetin (Q), Aconitine (A) and apoptosis induction affects human cervical carcinoma HeLa cells. The result of our findings ...shows that the combination of Q and A (QA) is capable of synergistically inhibiting the proliferation of HeLa cells in a number of concentrations. QA synergistically inhibits the proliferation of MDR1 gene in the HeLa cells. It is concluded based on our result that QA induces apoptosis and ER stress just as QA-induced ER stress pathway may mediate apoptosis by upregulating mRNA expression levels of eIF2α, ATF4, IRE1, XBP1, ATF6, PERK and CHOP in the HeLa cells. The up-regulating of mRNA expression level of GRP78 and activation of UPR are a molecular basis of QA-induced ER stress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Research Summary
Software platforms create value by cultivating an ecosystem of complementary products and services. Existing explanations for how a prospective complementor chooses platforms to join ...assume the complementor has rich information about the range of available platforms. However, complementors lack this information in many ecosystems, raising the question of how complementors learn about platforms in the first place. We investigate whether attending a temporary gathering—a hackathon—impacts the platform choices of software developers. Through a large‐scale quantitative study of 1,302 developers and 167 hackathons, supported by qualitative research, we analyze the multiple channels—sponsorship, social learning, knowledge exchange, and social coordination—through which hackathons serve as a social forum for the diffusion of platform adoption among attendees.
Managerial Summary
A software platform such as Windows, iOS, or Amazon Web Services relies on third‐party developers to create applications that complement the platform and make it valuable for end users. However, developers face a wide range of possible platforms, and they may have limited information about which platforms would be worthwhile to develop for. A software platform business can educate and encourage developers to adopt their platform by supporting in‐person software development competitions, known as hackathons. Developers learn about prospective platforms that advertise at the hackathon. Developers also learn whether and how to use a platform by observing and teaching one other. Hackathons are particularly useful for spreading platform technologies: developers prefer to adopt widely used platforms, and hackathons permit developers to identify and join fashionable platforms.
A 'Cu'te couple: A synthetically useful protocol for the preparation of N‐alkynylated sulfoximines (yne sulfoximines) has been developed. The method involves a mild copper‐catalyzed oxidative ...cross‐coupling of NH‐sulfoximines and terminal alkynes (see scheme). The corresponding N‐acyl sulfoximines were also obtained selectively after acid‐catalyzed hydrolysis of the yne sulfoximines.
•ECW could reduce the overall environmental impacts by 49.2% than conventional CW.•ECW could significantly reduce indirect and direct N2O emission.•Electricity consumption became the main ...environmental impacts source in all CWs.•ECW could save the overall costs of 61.8% and area of 65.0% than conventional CW.
The sustainability of the integrated bioelectrochemical-constructed wetland system (ECW) is still debatable. In this study, the environmental impact and economic performance of the conventionally constructed wetland (CW) and ECW were conducted using the life cycle assessment method. The results showed that both CW and ECW had significant impacts on the aquatic environment, especially on marine aquatic ecotoxicity. Although the application of the electrode module, especially the power supply, increased 118.0% of the environmental impacts from construction materials due to the massive use of plastics and metals, the overall environmental impact of ECW was 49.2% lower than that of the CW and the total global warming potential of ECW were mitigated by 69.1% compared with the CW. In terms of cost, the ECW could reduce 61.8% of the total cost when reaching the same effluent standard with the CW, indicating that ECW was environmentally and economically feasible.
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Background Diabetic foot ulcer (DFU) is a chronic infectious disease caused by diabetes mellitus (DM). Angiogenesis plays the decisive role in wound healing of DFU. Adipose-derived stem cells (ADSCs) ...can ameliorate angiogenesis in DFU by exosomes. This study aims to determine the mechanism of exosomes from mmu_circ_0001052-modified ADSCs in angiogenesis of DFU. Methods HUVECs were induced by high glucose and mice stimulated using STZ injection during high-fat feeding, which were treated with exosomes derived from mmu_circ_0001052-modified ADSCs. Real-time PCR determined the expression of gene and western blot determined protein levels. Proliferation, migration, apoptosis and angiogenesis of HUVECs were studied by MTT assay, transwell test, flow cytometry and tube formation experiment, respectively. Histological lesion of wound was determined by HE staining. Results The expression of circ_0001052 was upregulated in ADSCs and miR-106a-5p elevated in high glucose-induced HUVECs. Exosomal mmu_circ_0001052 significantly accelerated wound healing in mice with DFU. Also, exosomal mmu_circ_0001052 evoked the reduction of miR-106a-5p and the elevation of FGF4 in high glucose-induced HUVECs and wound tissue of DFU mice. Exosomal mmu_circ_0001052 was determined to sponge miR-106a-5p that targeted FGF4 in DFU. In high glucose-induced HUVECs, exosomal mmu_circ_0001052 inhibited apoptosis and miR-106a-5p expression, and meanwhile promoted proliferation, migration, angiogenesis and expressions of FGF4, VEGF and p-p38/p38, which were reversed by miR-106a-5p elevation. Conclusion Mmu_circ_0001052 in ADSCs-derived exosomes promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway. Graphical Keywords: Diabetic foot ulcer, mmu_circ_0001052, miR-106a-5p, FGF4/p38MAPK pathway, Angiogenesis
Aim The long-term stress, anxiety and job burnout experienced by healthcare workers (HCWs) are important to consider as the novel coronavirus disease (COVID-19) pandemic stresses healthcare systems ...globally. The primary objective was to examine the changes in the proportion of HCWs reporting stress, anxiety, and job burnout over six months during the peak of the pandemic in Singapore. The secondary objective was to examine the extent that objective job characteristics, HCW-perceived job factors, and HCW personal resources were associated with stress, anxiety, and job burnout. Method A sample of HCWs (doctors, nurses, allied health professionals, administrative and operations staff; N = 2744) was recruited via invitation to participate in an online survey from four tertiary hospitals. Data were gathered between March-August 2020, which included a 2-month lockdown period. HCWs completed monthly web-based self-reported assessments of stress (Perceived Stress Scale-4), anxiety (Generalized Anxiety Disorder-7), and job burnout (Physician Work Life Scale). Results The majority of the sample consisted of female HCWs (81%) and nurses (60%). Using random-intercept logistic regression models, elevated perceived stress, anxiety and job burnout were reported by 33%, 13%, and 24% of the overall sample at baseline respectively. The proportion of HCWs reporting stress and job burnout increased by approximately 1·0% and 1·2% respectively per month. Anxiety did not significantly increase. Working long hours was associated with higher odds, while teamwork and feeling appreciated at work were associated with lower odds, of stress, anxiety, and job burnout. Conclusions Perceived stress and job burnout showed a mild increase over six months, even after exiting the lockdown. Teamwork and feeling appreciated at work were protective and are targets for developing organizational interventions to mitigate expected poor outcomes among frontline HCWs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Protein glycosylation governs key physiological and pathological processes in human cells. Aberrant glycosylation is thus closely associated with disease progression. Mass spectrometry (MS)-based ...glycoproteomics has emerged as an indispensable tool for investigating glycosylation changes in biological samples with high sensitivity. Following rapid improvements in methodologies for reliable intact glycopeptide identification, site-specific quantification of glycopeptide macro- and micro-heterogeneity at the proteome scale has become an urgent need for exploring glycosylation regulations. Here, we summarize recent advances in N- and O-linked glycoproteomic quantification strategies and discuss their limitations. We further describe a strategy to propagate MS data for multilayered glycopeptide quantification, enabling a more comprehensive examination of global and site-specific glycosylation changes. Altogether, we show how quantitative glycoproteomics methods explore glycosylation regulation in human diseases and promote the discovery of biomarkers and therapeutic targets.
An unprecedented strategy to access highly enantioenriched dihydropyrazoles is described. It involves formal 4+1 cycloadditions of in situ-derived azoalkenes and sulfur ylides catalyzed by a chiral ...copper/Tol-BINAP complex. A variety of synthetically and biologically important dihydropyrazoles have been obtained with high enantioselectivities (up to 97:3 er) in good yields (83–97%).
In this work, we developed a miniaturized palmtop high-speed capillary electrophoresis (CE) system integrating whole modules, including picoliter-scale sample injection, short capillary-based fast ...CE, high-voltage power supply, orthogonal laser induced fluorescence (LIF) detection, battery, system control, on-line data acquisition, processing, storage, and display modules. A strategy of minimalist miniaturization combining minimal system design and low-cost system construction was adopted to achieve the instrument miniaturization with extremely low cost, which is differing from the current microfabrication strategy used in most reported miniaturized CE systems. With such a strategy, the total size of the bioanalyzer was minimized to 90 × 75 × 77 mm (length × width × height) and the instrument cost was reduced to ca. $500, which demonstrated the smallest and lowest-cost CE instrument with LIF detection in so far reported systems. The present bioanalyzer also exhibited comparable analytical performances to previously-reported high-speed CE systems. A limit of detection of 1.02 nM sodium fluorescein was obtained. Fast separations were achieved for multiple types of samples as amino acids, amino acid enantiomers, DNA fragments, and proteins with high efficiency. We applied this instrument in colorectal cancer diagnosis for detecting KRAS mutation status by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and ...accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification. The N-glycoproteome of samples metabolically labeled with
N/
C were analyzed quantitatively and utilized to validate the glycopeptide identification, which could be used as a novel benchmark pipeline to compare different search engines. Finally, we report a large-scale glycoproteome dataset consisting of 10,009 distinct site-specific N-glycans on 1988 glycosylation sites from 955 glycoproteins in five mouse tissues.Protein glycosylation is a heterogeneous post-translational modification that generates greater proteomic diversity that is difficult to analyze. Here the authors describe pGlyco 2.0, a workflow for the precise one step identification of intact N-glycopeptides at the proteome scale.
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