Photochemical site-selective synthesis of [70]methanofullerenes

Methanofullerenes such as the well-known [70]PCBM are commonly synthesized under harsh conditions to obtain the product as a mixture of site-isomers (namely a, b and minor c) due to the D5h symmetry of the C70 cage. We report the first site-selective synthesis of [70]methanofullerenes under light irradiation and low temperatures, thus avoiding time-consuming and highly expensive HPLC separations. Pure major site-isomers a-[70]PCBM and a-[70]DPM have been thus efficiently prepared including the crystal structure of 5b. Photovoltaic preliminary results revealed a slightly beneficial performance for a-pure [70]PCBM site-isomer devices

A fuzzy ordinary regression method for modeling customer preference in tea maker design

Faced with fierce competition in marketplaces, manufacturers need to determine the appropriate settings of engineering characteristics of the new products so that the best customer preferences of the products can be obtained. To achieve this, functional models relating customer preferences to engineering characteristics need to be developed. As information regarding functional relationships between customer preferences are generally subjective or heuristic in nature, development of the customer preference models involve two uncertainties, namely fuzziness and randomness. Existing approaches use only fuzzy-based technologies to address the uncertainty caused by fuzziness. They are not designed to address the randomness of the observed data which is caused by a limited knowledge of the variability of influences between customer preferences and engineering characteristics. In this article, a fuzzy ordinary regression method is proposed to develop the customer preference models which are capable of addressing the two uncertainties of crispness and fuzziness of the customer preferences. A case study of a tea maker design which involves both uncertainties is used to demonstrate the effectiveness of the proposed method

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Roles of non-institutional investors in private placements

I study the announcement returns and the post-placement performance by looking at the identities of investors in the private placements. I find that the participations of individual investors and the management are crucial and associated with significant positive announcement returns of 3.5% and 6.3% respectively, after controlling the firm characteristics and placement terms. Portfolios forming according to the participations of the individual investors and the management generate significant positive weekly alphas of 0.25% and 0.34% respectively, which is equivalent to 13.9% and 19.3% annually. The effects are consistent for the announcement returns and post-placement performance, under the explanation of monitoring hypothesis and certification hypothesis. The findings suggest that the non-ins6tu6onal investors are better informed and their participations provide better certification effects on the stock price. Management participation further improves the post-placement performance by reducing the agency cost. Participation of individual investors improves the post-placement performance by better monitoring, with mere participation of other institutional investors. I also find that the number of institutional investors participated in the placements has a negative effect on the announcement returns, suggesting the increase in the number associates with little certification and hinders the monitoring by creating a free-rider problem. All the results are robust to the choice of estimation models.published_or_final_versionEconomics and FinanceMasterMaster of Philosoph

Hypoxia-induced Changes to Integrin α 3 Glycosylation Facilitate Invasion in Epidermoid Carcinoma Cell Line A431

Hypoxia is a critical microenvironmental factor that drives cancer progression through angiogenesis and metastasis. Glycoproteins, especially those on the plasma membrane, orchestrate this process; however, questions remain regarding hypoxia-perturbed protein glycosylation in cancer cells. We focused on the effects of hypoxia on the integrin family of glycoproteins, which are central to the cellular processes of attachment and migration and have been linked with cancer in humans. We employed electrostatic repulsion hydrophilic interaction chromatography coupled with iTRAQ labeling and LC-MS/MS to identify and quantify glycoproteins expressed in A431. The results revealed that independent of the protein-level change, N-glycosylation modifications of integrin α 3 (ITGA3) were inhibited by hypoxia, unlike in other integrin subunits. A combination of Western blot, flow cytometry, and cell staining assays showed that hypoxia-induced alterations to the glycosylation of ITGA3 prevented its efficient translocation to the plasma membrane. Mutagenesis studies demonstrated that simultaneous mutation of glycosites 6 and 7 of ITGA3 prevented its accumulation at the K562 cell surface, which blocked integrin α 3 and β 1 heterodimer formation and thus abolished ITGA3's interaction with extracellular ligands. By generating A431 cells stably expressing ITGA3 mutated at glycosites 6 and 7, we showed that lower levels of ITGA3 on the cell surface, as induced by hypoxia, conferred an increased invasive ability to cancer cells in vitro under hypoxic conditions. Taken together, these results revealed that ITGA3 translocation to the plasma membrane suppressed by hypoxia through inhibition of glycosylation facilitated cell invasion in A431.NMRC (Natl Medical Research Council, S’pore)Accepted versio

Microalgal-based biochar in wastewater remediation: its synthesis, characterization and applications

Microalgae are drawing attentions among researchers for their biorefinery use or value-added products. The high production rate of biomasses produced are attractive for conversion into volatile biochar. Torrefaction, pyrolysis and hydrothermal carbonization are the recommended thermochemical conversion techniques that could produce microalgal-based biochar with desirable physiochemical properties such as high surface area and pore volume, abundant surface functional groups, as well as functionality such as high adsorption capacity. The characterizations of the biochar significantly influence the mechanisms in adsorption of pollutants from wastewaters. Specific adsorption of the organic and inorganic pollutants from the effluent are reviewed to examine the adsorption capacity and efficiency of biochar derived from different microalgae species. Last but not least, future remarks over the challenges and improvements are discussed accordingly. Overall, this review would discuss the synthesis, characterization and application of the microalgal-based biochar in wastewater

Acetylshikonin, a Novel AChE Inhibitor, Inhibits Apoptosis via Upregulation of Heme Oxygenase-1 Expression in SH-SY5Y Cells

Acetylcholinesterase inhibitors are prominent alternative in current clinical treatment for AD patients. Therefore, there is a continued need to search for novel AChEIs with good clinical efficacy and less side effects. By using our in-house natural product database and AutoDock Vina as a tool in docking study, we have identified twelve phytochemicals (emodin, aloe-emodin, chrysophanol, and rhein in Rhei Radix Et Rhizoma; xanthotoxin, phellopterin, alloisoimperatorin, and imperatorin in Angelicae dahuricae Radix; shikonin, acetylshikonin, isovalerylshikonin, and β,β-dimethylacrylshikonin in Arnebiae Radix) as candidates of AChEIs that were not previously reported in the literature. In addition to AChEI activity, a series of cell-based experiments were conducted for the investigation of their neuroprotective activities. We found that acetylshikonin and its derivatives prevented apoptotic cell death induced by hydrogen peroxide in human and rat neuronal SH-SY5Y and PC12 cells at 10 μM. We showed that acetylshikonin exhibited the most potent antiapoptosis activity through the inhibition of the generation of reactive oxygen species as well as protection of the loss of mitochondria membrane potential. Furthermore, we identified for the first time that the upregulation of heme oxygenase 1 by acetylshikonin is a key step mediating its antiapoptotic activity from oxidative stress in SH-SY5Y cells