Yang et al. show that a disulfide isoform of HMGB1, with a role in TLR4 signaling, physically interacts with and binds MD-2. MD-2 deficiency in macrophage cell lines or in primary mouse macrophages stimulated with HMGB1 implicates MD-2 in TLR4 signaling. They also identify an HGMB1 peptide inhibitor, P5779, which when administered in vivo can protect mice from acetaminophen-induced hepatoxicity, ischemia/reperfusion injury, and sepsis.

Neurotrauma is one of the most serious traumatic injuries, which can induce an excess amount of reactive oxygen and nitrogen species (RONS) around the wound, triggering a series of biochemical responses and neuroinflammation. Traditional antioxidant-based bandages can effectively decrease infection via preventing oxidative stress, but its effectiveness is limited to a short period of time due to the rapid loss of electron-donating ability. Herein, we developed a nanozyme-based bandage using single-atom Pt/CeO2 with a persistent catalytic activity for noninvasive treatment of neurotrauma. Single-atom Pt induced the lattice expansion and preferred distribution on (111) facets of CeO2, enormously increasing the endogenous catalytic activity. Pt/CeO2 showed a 2–10 times higher scavenging activity against RONS as well as 3–10 times higher multienzyme activities compared to CeO2 clusters. The single-atom Pt/CeO2 retained the long-lasting catalytic activity for up to a month without obvious decay due to enhanced electron donation through the Mars–van Krevelen reaction. In vivo studies disclosed that the nanozyme-based bandage at the single-atom level can significantly improve the wound healing of neurotrauma and reduce neuroinflammation.

Abstract. Bi, a high atom number element, has a high photoelectric absorption coefficient, and Se element has anticancer activity. Hence, their compound chalcogenide (Bi 2 Se 3 ) deserves a thorough investigation for biomedical applications. This study reveals that Bi 2 Se 3 nanoplates (54 nm wide) protected with poly(vinylpyrollidone) (PVP) are biocompatible and have low toxicity even at a high dose of 20 mg/kg in mice. This conclusion was made through the studies on the biodistribution and 90-day long term in vivo clearance of the nanoplates.Liver and spleen were dominant organs for the nanoplates accumulation which was mainly due to RES absorption, but 93 % the nanoplates were cleared after 90 days treatment.

Ionizing radiation (gamma and X-ray) is widely used in industry and medicine, but it can also pose a significant hazardous effect on health and induce cancer, physical deformity, and even death, due to DNA damage and invasion of free radicals. There is therefore an urgent unmet demand in designing highly efficient radioprotectants with synergetic integration of effective renal clearance and low toxicity. In this study, we designed ultrasmall (sub-5 nm) highly catalytically active and cysteine-protected MoS2 dots as radioprotectants and investigated their application in protection against ionizing radiation. In vivo preclinical studies showed that the surviving fraction of MoS2-treated mice can appreciably increase to up to 79% when they were exposed to high-energy ionizing radiation. Furthermore, MoS2 dots can contribute in cleaning up the accumulated free radicals within the body, repairing DNA damage, and recovering all vital chemical and biochemical indicators, suggesting their unique role as free radical scavengers. MoS2 dots showed rapid and efficient urinary excretion with more than 80% injected dose eliminated from the body after 24 h due to their ultrasmall hydrodynamic size and did not cause any noticeable toxic responses up to 30 days.

Water deficit imposed by either drought or salinity brings about severe growth retardation and yield loss of crops. Since Brassica crops are important contributors to total oilseed production, it is urgently needed to develop tolerant cultivars to ensure yields under such adverse conditions. There are various physiochemical mechanisms for dealing with drought and salinity in plants at different developmental stages. Accordingly, different indicators of tolerance to drought or salinity at the germination, seedling, flowering and mature stages have been developed and used for germplasm screening and selection in breeding practices. Classical genetic and modern genomic approaches coupled with precise phenotyping have boosted the unravelling of genes and metabolic pathways conferring drought or salt tolerance in crops. QTL mapping of drought and salt tolerance has provided several dozen target QTLs in Brassica and the closely related Arabidopsis. Many drought- or salt-tolerant genes have also been isolated, some of which have been confirmed to have great potential for genetic improvement of plant tolerance. It has been suggested that molecular breeding approaches, such as marker-assisted selection and gene transformation, that will enhance oil product security under a changing climate be integrated in the development of drought- and salt-tolerant Brassica crops.

Metal nanozyme has attracted wide interest for biomedicine, and a highly catalytic material in the physiological environment is highly desired. However, catalytic selectivity of nanozyme is still highly challenging, limiting its wide application. Here, we show a trimetallic (triM) nanozyme with highly catalytic activity and environmental selectivity. Enzyme-mimicked investigations find that the triM system possesses multi-enzyme-mimetic activity for removing reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as 1O2, H2O2, •OH, and •NO. Importantly, triM nanozyme exhibits the significant neutral environment preference for removing the •OH, 1O2, and •NO free radical, indicating its highly catalytic selectivity. The density functional theory (DFT) calculations reveal that triM nanozyme can capture electrons very easily and provides more attraction to reactive oxygen and nitrogen species (RONS) radicals in the neutral environment. In vitro experiments show that triM nanozyme can improve the viability of injured neural cell. In the LPS-induced brain injury model, the superoxide dismutase (SOD) activity and lipid peroxidation can be greatly recovered after triM nanozyme treatment. Moreover, the triM nanozyme treatment can significantly improve the survival rate, neuroinflammation, and reference memory of injured mice. Present work provides a feasible route for improving selectivity of nanozyme in the physiological environment as well as exploring potential applications in brain science.

Background: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS.

Reactive oxygen and nitrogen species (RONS), especially reactive nitrogen species (RNS) are intermediate products during incidence of nervous system diseases, showing continuous damage for traumatic brain injury (TBI). Here, we developed a carbogenic nanozyme, which shows an antioxidant activity 12 times higher than ascorbic acid (AA) and behaves as multienzyme mimetics. Importantly, the nanozyme exhibits an ultrahigh scavenging efficiency (∼16 times higher than AA) toward highly active RNS, such as •NO and ONOO– as well as traditional reactive oxygen species (ROS) including O2 •–, H2O2, and •OH. In vitro experiments show that neuron cells injured by H2O2 or lipopolysaccharide can be significantly recovered after carbogenic nanozyme treatment via scavenging all kinds of RONS. Moreover, the carbogenic nanozyme can serve as various enzyme mimetics and eliminate the harmful peroxide and glutathione disulfide from injured mice, demonstrating its potential as a therapeutic for acute TBI.