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Inflammation is a complex physiological process that poses a serious threat to people’s health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro . Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.

Malicious cyber activities against space activities (MCASAs) add to the complexities of the legal attribution of malicious cyber activities violating international law. The ‘space’ implies the possibility of applying international space law considering the lex specialis derogat legi generali (more specific rules will prevail over more general rules) principle. However, neither the attribution rules of international space law nor of general international law could completely tackle this dilemma. This study categorizes MCASAs into three categories based on the role of the involved space activities and analyses the crux of legal attribution in each scenario. It proposes different coping approaches, including a four-pronged way, introducing a peculiarity test, and specifying substantive international obligations of the states responsible for space activities.

The sluggish kinetics of the hydrogen evolution reaction in base has resulted in large activity gap between acidic and alkaline electrolytes. Here, we present an intermetallic IrMo electrocatalyst supported on carbon nanotubes that exhibits a specific activity of 0.95 mA cm −2 at the overpotential of 15 mV, which is 14.4 and 9.5 times of those for Ir/C and Pt/C, respectively. More importantly, its activities in base are fairly close to that in acidic electrolyte and the activity gap between acidic and alkaline media is only one fourth of that for Ir/C. DFT calculations reveal that the stably-adsorbed OH spectator at Mo site of IrMo can stabilize the water dissociation product, resulting in a thermodynamically favorable water dissociation process. Beyond offering an advanced electrocatalyst, this work provides a guidance to rationally design the desirable HER electrocatalysts for alkaline water splitting by the stably-adsorbed OH spectator. While alkaline water electrolysis offers a green means for hydrogen production, H 2 -evolving catalysts typically show worse activities in alkaline media than in acid. Here, authors examine IrMo intermetallics as electrocatalysts and identify a stably-adsorbed OH spectator in promoting performances.

Common bean ( Phaseolus vulgaris ) seeds are important legume crops and an important source of dietary proteins and carbohydrates. Therefore, it is important to develop strategies to improve salt tolerance in common beans. In this study, transcriptome and metabolome analyses were conducted on local common bean variety under salt stress at the sprout stage for a period of 0, 12, and 24 h. Results showed that phenylpropanoid pathways (including phenylpropanoid biosynthesis and phenylalanine metabolism) and flavonoid pathways (including flavonoid biosynthesis and flavone and flavonol biosynthesis) played an important role in controlling responses to salt stress as evidenced by analysis of differentially expression genes, common expression patterns, WCGNA, and differentially altered metabolites (DAMs) analyses. In addition, exploration of the activities of 4‐coumarate‐CoA ligase (4CL), caffeoyl‐CoA O‐methyltransferase (CCoAOMT), peroxidase (POD), chalcone isomerase (CHI), dihydroflavonol‐4‐reductase (DFR), and flavonol synthase (FLS) further showed that phenylpropanoid and flavonoid pathways participate in plant responses to salt stress. Moreover, the phenylpropanoid pathways and flavonoid pathways were found to be potential pathways regulating plant response to salt stress based on transcriptome and metabolome analysis. The activities of 4CL, CCoAOMT, POD, CHI, DFR, and FLS revealed that these pathways are crucial to the regulation of plant responses to salt stress. These findings provided theoretical basis for further improvement of salt tolerance in common bean.

Background This study examines how the prevalence of depression and anxiety symptoms differ by socioeconomic status and explores their associations with diabetes in rural southwest China. Methods Data were collected from a cross-sectional health interview and examination survey of 5,005 adults aged ≥ 35 years in rural southwest China. Height, weight, waist circumference, and fasting blood glucose measurement were taken. Depression and anxiety symptoms were assessed using Zung’s Self-rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS), respectively. An individual socioeconomic position (SEP) index was constructed using principal component analysis. Results The overall prevalence of depression, anxiety, comorbid depression and anxiety symptoms, and diabetes was 5.4%, 12.8%, 4.0%, and 9.6%, respectively. Females had higher prevalence of depression (7.3% vs. 3.4%, P  < 0.01), anxiety (17.4% vs. 8.1%, P  < 0.01), and comorbid depression and anxiety symptoms (5.8% vs. 2.3%, P  < 0.01) than males. Han ethnicity participants had a higher prevalence of depression, anxiety, and comorbid depression and anxiety symptoms than ethnic minority participants ( P  < 0.01). Individuals with a lower education level and lower SEP were more likely to experience depression, anxiety, and comorbid depression and anxiety symptoms ( P  < 0.01), while individuals with good access to medical services were more likely to exhibit depression symptoms and comorbid depression and anxiety symptoms ( P  < 0.05). Multivariable logistic regression analysis found that individuals with depression symptoms (OR = 1.78, 95% CI: 1.25 to 2.53), anxiety symptoms (OR = 1.66, 95% CI: 1.30 to 2.16), and comorbid depression and anxiety symptoms (OR = 1.61, 95% CI: 1.07 to 2.44) all had a greater probability of having diabetes ( P  < 0.01); depression symptoms had the strongest association with diabetes prevalence ( P  < 0.01). Conclusions There are significant socioeconomic differences in the prevalence of depression and anxiety in rural southwest China, and both depression and anxiety symptoms have strong associations with diabetes. Future diabetes prevention and management strategies should focus on individuals with depression, anxiety, and comorbid depression and anxiety symptoms.

Multiphoton fluorescence microscopy (MPM), using near infrared excitation light, provides increased penetration depth, decreased detection background, and reduced phototoxicity. Using stimulated emission depletion (STED) approach, MPM can bypass the diffraction limitation, but it requires both spatial alignment and temporal synchronization of high power (femtosecond) lasers, which is limited by the inefficiency of the probes. Here, we report that upconversion nanoparticles (UCNPs) can unlock a new mode of near-infrared emission saturation (NIRES) nanoscopy for deep tissue super-resolution imaging with excitation intensity several orders of magnitude lower than that required by conventional MPM dyes. Using a doughnut beam excitation from a 980 nm diode laser and detecting at 800 nm, we achieve a resolution of sub 50 nm, 1/20th of the excitation wavelength, in imaging of single UCNP through 93 μm thick liver tissue. This method offers a simple solution for deep tissue super resolution imaging and single molecule tracking. Upconversion nanoparticles offer the potential for deep tissue biological imaging. Here, Chen et al. develop super resolution optical imaging in the near-infrared for imaging with sub-50 nm resolution through almost 100 microns of tissue.

Background Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. Results We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to “generalists.” Notably, Bandavirus dabieense , the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. Conclusions These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. 4querEumuJMtVvn4JLJ-5M Video Abstract

Background Hyperuricemia predisposes to gout, which may result in tophi, kidney stones, or urate nephropathy even kidney failure. Many metabolic risk factors and disorders has been recognized as a key risk factor contributing to development of hyperuricemia. Aim To determine the prevalence of hyperuricemia and its association with adiposity and dyslipidemia. Methods We recruited non-hospitalized participants (aged ≥35 years) in Xinjiang, a northwest part of China based on the Cardiovascular Risk Survey (CRS 2008–2012). Information of general health status, seafood or internal organs intake and history of disease were obtained by using an interview-based questionnaire. The levels of serum uric acid (sUA) and creatinine and lipid profiles were measured. A multivariate logistic regression model was performed to assess the association between prevalence of hyperuricemia and adiposity and dyslipidemia. Results This study recruited 16,611 participants, and 14,618 was included (mean age of 50.5 ± 12.6 years, 46.6% was males). The study population comprised three ethnic groups with 39.4% of Han, 32.6% of Uygur and 28% of Kazakh Chinese. The overall prevalence of hyperuricemia was 9.1% (95% CI: 8.6 to 9.6) and it was11.8% in men was 6.7% in women. The three ethnic groups also had different hyperuricemia prevalence with 15.4% in Han, 4.6% in Uygur and 5.5% in Kazakh Chinese, which corresponding to a respective mean sUA levels of 306.2 ± 86.9, 249.4 ± 76.1 and 259.8 ± 78.7 μmol/L. Participants with diabetes, hypertension or hypertriglyceridemia and higher blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC) had higher levels of sUA ( P  < 0.001 respectively). Multivariate logistic regression analysis revealed that age, gender, ethnicity, drinking, obesity, waist circumference, TG (≥2.26 mmol/L), TC (≥6.22 mmol/L) are major risk factors for hyperuricemia. Compared to the 35–44-year age group [adjusted odds ratio (AOR) = 1], the risk of hyperuricemia increased 1.61-fold in the 65–74-year age group (AOR = 1.61, 95% CI: 1.34–1.91; P  < 0.001), and 1.71-fold in the 75- and older age group (AOR = 1.71, 95% CI: 1.27–2.29; P  < 0.001). There was a 1.45-fold higher risk of hyperuricemia in men (AOR = 1.45, 95% CI: 1.24–1.68; P  < 0.001) compared to women. Further, the risk of hyperuricemia increased significantly with drinking (AOR = 1.36; 95% CI: 1.16–1.61; P  < 0.001), overweight (AOR = 1.25; 95% CI: 1.06–1.48; P  = 0.01), obesity (AOR = 1.28; 95% CI: 1.10–1.49; P  < 0.001), waist circumference (AOR = 1.48; 95% CI: 1.24–1.78; P  < 0.001), TC (≥6.22 mmol/L, AOR = 1.45; 95% CI: 1.19–1.75; P  < 0.001), TG (≥2.26 mmol/L, AOR = 2.74; 95% CI: 2.39–3.14; P  < 0.001). Conclusions These findings documented that the hyperuricemia is prevalent in the economically developing regions of northwest China. Hyperuricemia is associated with advanced age, male ender and general metabolic and cardiovascular risk factors. Obesity and dyslipidemia increase the risk of hyperuricemia.