HMGB1 in health and disease

Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed high-mobility group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhibitors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localization, structure, post-translational modification, and identification of additional partners will undoubtedly uncover additional secrets regarding HMGB1\u27s multiple functions. (C) 2014 Elsevier Ltd. All rights reserved

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Chemical characterization and source apportionment of PM2.5 in Beijing: seasonal perspective

PM2.5 samples were collected at six general stations and one roadside station in Hong Kong in two periods of high particulate matter (PM) in 2003 (27 October&ndash;4 November and 30 November&ndash;13 December). The highest PM2.5 reached 216 &mu;g m&minus;3 during the first high PM period and 113 &mu;g m&minus;3 during the second high PM period. Analysis of synoptic weather conditions identified individual sampling days under dominant influence of one of three types of air masses, that is, local, regional and long‐range transported (LRT) air masses. Roadside samples were discussed separately due to heavy influences from vehicular emissions. This research examines source apportionment of fine organic carbon (OC) and contribution of secondary organic aerosol on high PM days under different synoptic conditions. Six primary OC (POC) sources (vehicle exhaust, biomass burning, cooking, cigarette smoke, vegetative detritus, and coal combustion) were identified on the basis of characteristic organic tracers. Individual POC source contributions were estimated using chemical mass balance model. In the roadside and the local samples, OC was dominated by the primary sources, accounting for more than 74% of OC. In the samples influenced by regional and LRT air masses, secondary OC (SOC), which was approximated to be the difference between the total measured OC and the apportioned POC, contributed more than 54% of fine OC. SOC was highly correlated with water‐ soluble organic carbon and sulfate, consistent with its secondary nature.</p

“Chemical characterization and source apportionment of PM2.5in Beijing: seasonal perspective” published in Atmos. Chem. Phys.,13, 7053–7074, 2013

No abstract available

Impact of biomass burning on haze pollution in the Yangtze River delta, China: a case study in summer 2011

Open biomass burning is an important source of air pollution in China and globally. Joint observations of air pollution were conducted in five cities (Shanghai, Hangzhou, Ningbo, Suzhou and Nanjing) of the Yangtze River delta, and a heavy haze episode with visibility 2.9-9.8 km was observed from 28 May to 6 June 2011. The contribution of biomass burning was quantified using both ambient monitoring data and the WRF/CMAQ (Weather Research and Forecasting (WRF) and Community Multiscale Air Quality (CMAQ)) model simulation. It was found that the average and maximum daily PM2.5 concentrations during the episode were 82 and 144 mu gm(-3), respectively. Weather pattern analysis indicated that stagnation enhanced the accumulation of air pollutants, while the following precipitation event scavenged the pollution. Mixing depth during the stagnant period was 240-399 m. Estimation based on observation data and CMAQ model simulation indicated that biomass open burning contributed 37% of PM2.5, 70% of organic carbon and 61% of elemental carbon. Satellite-detected fire spots, back-trajectory analysis and air quality model simulation were integrated to identify the locations where the biomass was burned and the pollutants transport. The results suggested that the impact of biomass open burning is regional, due to the substantial inter-province transport of air pollutants. PM2.5 exposure level could be reduced 47% for the YRD region if complete biomass burning is forbidden and significant health benefit is expected. These findings could improve the understanding of heavy haze pollution, and suggest the need to ban open biomass burning during post-harvest seasons.</p