Macrophages are highly heterogeneous and exhibit a diversity of functions and phenotypes. They can be divided into pro‐inflammatory macrophages (M1) and anti‐inflammatory macrophages (M2). Diabetic ...wounds are characterized by a prolonged inflammatory phase and difficulty in healing due to the accumulation of pro‐inflammatory (M1) macrophages in the wound. Therefore, hydrogel dressings with macrophage heterogeneity regulation function hold great promise in promoting diabetic wound healing in clinical applications. However, the precise conversion of pro‐inflammatory M1 to anti‐inflammatory M2 macrophages by simple and biosafe approaches is still a great challenge. Here, an all‐natural hydrogel with the ability to regulate macrophage heterogeneity is developed to promote angiogenesis and diabetic wound healing. The protocatechuic aldehyde hybridized collagen‐based all‐natural hydrogel exhibits good bioadhesive and antibacterial properties as well as reactive oxygen species scavenging ability. More importantly, the hydrogel is able to convert M1 macrophages into M2 macrophages without the need for any additional ingredients or external intervention. This simple and safe immunomodulatory approach shows great application potential for shortening the inflammatory phase of diabetic wound repair and accelerating wound healing.
An all‐natural hydrogel composed of small molecules pro‐catechol and collagen is developed to promote diabetic wound healing by modulating macrophage heterogeneity. The hydrogel exhibits good bioadhesive, antibacterial, and reactive oxygen species scavenging abilities. In vitro and in vivo experiments show that the hydrogel is able to promote the conversion of pro‐inflammatory (M1) macrophages to anti‐inflammatory (M2) macrophages and the expression of anti‐inflammatory factors.
A heavy load of nitrogenous compounds reflects nutrient loss and influences water quality in large rivers. Nitrogenous concentrations and dual isotopes of nitrate were measured to ascertain the ...spatial and temporal distributions of nitrate transformation in the Yellow River, the second-longest river in China. Assessment of the long-term record indicates that NO
-N has increased by two-fold over the past three decades. Weekly observation of ammonium over a twelve-year period revealed high concentrations and suggests impairment of water quality, particularly since 2011. The estimated total dissolved nitrogen flux was 7.2 times higher in middle reaches than that at head waters. Anthropogenic nitrogen sources become more important in lower section of the upper reaches and middle reaches because of intensive agricultural activities and urban input. Nitrate in the lower reaches was mainly derived from transportation of upstream nitrate and point sources from cities. The spatial variation of ammonium and nitrate isotopes show that nitrification is a key process governing nitrogen transformation. Riverine biological processes could potentially be responsible for the shift of nitrate isotope signature. The first step to reducing nitrogen load and improving water quality will be containment and careful management of sources from urban input, sewage waste and irrigation runoff.
Summary
This is a meta‐analysis of the pooled prevalence of sleep disturbances and its associated factors in Chinese university students. English (PubMed, PsycINFO, Embase) and Chinese (SinoMed, Wan ...Fang Database and Chinese National Knowledge Infrastructure) databases were systematically and independently searched from inception until 16 August 2016. The prevalence of sleep disturbances was pooled using random‐effects model. Altogether 76 studies involving 112 939 university students were included. The overall pooled prevalence of sleep disturbances was 25.7% (95% CI: 22.5–28.9%). When using the screening scales Pittsburgh Sleep Quality Index, Athens Insomnia Scale and Self‐Rating Sleeping State Scale, and the diagnostic criteria of the Chinese Classification of Mental Disorders (Second Edition), the pooled prevalence of sleep disturbances was 24.1% (95% CI: 21.0–27.5%) and 18.1% (95% CI: 16.4–20.0%), respectively. The percentages of students dissatisfied with sleep quality and those suffering from insomnia symptoms were 20.3% (95% CI: 13.0–30.3%) and 23.6% (95% CI: 18.9–29.0%), respectively. Subgroup analyses revealed that medical students were more vulnerable to sleep disturbances than other student groups. There was no significant difference between males and females, and across geographic locations. Sleep disturbances are common in Chinese university students. Appropriate strategies for prevention and treatment of sleep disturbances in this population need greater attention.
PCR amplification indicated the minimum infection rate of Rickettsia spp. was 0.66% in Haemaphysalis longicornis ticks collected from Shandong Province, China. Phylogenetic analysis based on the rrs, ...gltA, ompA, and ompB genes indicated that the ticks carried R. japonica, Candidatus Rickettsia longicornii, and a novel Rickettsia species related to R. canadensis.
This paper is devoted to establishing a nonlinear constitutive model incorporating crack closure effect for capturing the whole process of rock deformation and failure behavior under compression. The ...model formulated in the framework of irreversible thermodynamics is based on the additive decomposition of the total strain into crack closure strain, elastic, and plastic parts. New specific criteria are proposed for the description of crack closure strain and plastic strain evolution. Notably, analytical solutions of the model under conventional triaxial compression loading conditions are derived. For application, a robust semi‐implicit return mapping (SRM) algorithm with a crack closure strain correction and a plastic strain correction is developed. The analytical solutions, herein, are subtly used to calibrate model parameters and as reference results for assessing the accuracy and robustness of the SRM algorithm. Validation of the model conducted by comparing with experimental data from the literature shows that the model can properly describe the nonlinear mechanical behaviors of rocks, including crack closure effect, strain hardening/softening, peak and residual strength, as well as volumetric compaction/dilation transition. In addition, a nonlocal formulation is introduced as an extension of the model to remedy the mesh dependency problem.
BRAF mutations have been well described in non-small cell lung cancer (NSCLC) for several years, but the clinical features of patients harboring BRAF mutations are still not well described. We ...performed a meta-analysis to identify common clinical features in NSCLC patients carrying BRAF mutations.
We identified clinical studies that examined the association between BRAF mutations and features of NSCLC within PubMed, Embase and ISI Science Citation Index database up to October 2013. The effect size of clinical features was estimated by odds ratios (ORs) with 95% confidence interval (CI) for each study, using a fixed-effects or random-effects model.
Ten studies with a total of 5599 NSCLC patients were included. There was a 3% (170/5599) BRAF mutation rate. BRAF mutations in NSCLC were significantly associated with adenocarcinomas (ADCs) (compared with non-ADCs, OR = 4.96, 95%CI = 2.29-10.75). There were no significant differences in gender, smoking and stage in patients with and without BRAF mutations. The BRAFV600E mutation was more frequent in women than non-BRAFV600E mutations (OR = 0.27, 95%CI = 0.12-0.59), and was closely related to never smokers (OR = 0.14, 95%CI = 0.05-0.42).
These findings have important implications for the prediction of the NSCLC sub-types more accurately combined with other genetic changes.
Glucose‐6‐phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP) and plays an essential role in the oxidative stress response by producing NADPH, the main intracellular ...reductant. G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. Here, we show that G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays a complete loss of activity. Knockdown of G6PD sensitizes cells to oxidative stress, and re‐expression of wild‐type G6PD, but not the K403 acetylation mimetic mutant, rescues cells from oxidative injury. Moreover, we show that cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2‐dependent manner. The SIRT2‐mediated deacetylation and activation of G6PD stimulates PPP to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes. We also identified KAT9/ELP3 as a potential acetyltransferase of G6PD. Our study uncovers a previously unknown mechanism by which acetylation negatively regulates G6PD activity to maintain cellular NADPH homeostasis during oxidative stress.
Synopsis
The pentose phosphate pathway plays an important role in the oxidative stress response by supplying the reductant NADPH. SIRT2‐mediated deacetylation and activation of the glucose‐6‐phosphate dehydrogenase, the rate‐limiting enzyme in this pathway, stimulates the production of cytosolic NADPH to counteract oxidative damage.
K403 acetylation decreases G6PD activity by inhibiting dimer formation.
SIRT2 and KAT9/ELP3 regulate G6PD K403 acetylation.
Regulation of G6PD K403 acetylation modulates NADPH homeostasis and cell survival during oxidative stress.
Following oxidative stress, production of the reductant NADPH via the pentose phosphate pathway is stimulated by SIRT2‐mediated deacetylation and activation of G6PD.
Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal ...flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.
Background： The emergency department （ED） has a pivotal influence on the management of acute heart failure （AHF）, but dataconcerning current ED management are scarce. This Beijing AHF Registry Study ...investigated the characteristics. ED management, and short- and long-term clinical outcomes of AHF. Methods： This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median （interquartile range） for the continuous variables, or as number （percentage） for the categorical variables. Results： The median age of the enrolled patients was 71 （58 79） years, and 46.84% wvere women. In patients with AHH coronary heart disease （43.27%） was the most common etiology, andmyocardium ischemia （30.22%） was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics （79.28%） and vasodilators （74.90%）. Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively. Conclusions： Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.
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