Identification, molecular docking, and protective effects on H2O2-induced HEK-293 cell oxidative damage of antioxidant peptides from Pacific saury (Cololabis saira).

We identified novel antioxidant peptides from Pacific saury (Cololabis saira). Enzymatic hydrolysates were isolated, purified, and identified by ultrafiltration, gel chromatography, reverse phase high-performance liquid chromatography (RP-HPLC), and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS). Twenty putative peptides were identified from five components of HPLC, among which sixteen peptides were predicted to have good water solubility and non-toxicity by online tools. Fifteen peptides were successfully docked with myeloperoxidase, and we observed that Arg31, Arg323, and Lys505 played a key role in the antioxidant mechanism, with van der Waals forces and conventional hydrogen bonds as important interaction forces. Six identified peptides with lower CDOCKER energy values were synthesized to verify the antioxidant activity, and the results showed that the synthetic peptide QQAAGDKIMK displayed the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate (31.05 ± 0.27%) and reducing power (0.29 ± 0.01). The synthetic peptide KDEPDQASSK at a concentration of 300 µg mL-1 exhibited the strongest protective effects on H2O2-induced oxidative damage of HEK-293 cells, with cell viability and ROS level of 0.38 ± 0.03 and 0.08 ± 0.01, respectively.

Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy.

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.

Ambient fine particulate matter exposures and human early placental inflammation.

The effect of fine particulate matter (PM2.5) on human early maternal-fetal interface is unknown. We explored the association between maternal exposure to ambient PM2.5 and inflammation in placental villus of 114 women with clinically recognized early pregnancy loss (CREPL) and 114 women with normal early pregnancy (NEP). Temporally-adjusted land use regression models were used to estimate maternal daily PM2.5 exposure during pregnancy. Villus interleukin-1beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured using multiplex cytokines detection platform. Single-day lag effect of PM2.5 exposure within ten days before early placental villus collection was estimated using multivariable linear regression model. Distributed lag and net cumulative effects of PM2.5 exposures within ten and 30 days before villus collection, as well as five single weeks during the periovulatory period, were estimated using distributed lag non-linear models. In all 228 subjects, after adjusting for group (CREPL or NEP), temporal confounders, and demographic characteristics, both single-day and distributed lag effects of PM2.5 exposure at lag 8 significantly increased villus IL-6; distributed lag effects of PM2.5 exposure in the first and second weeks before ovulation increased IL-1ß, and PM2.5 exposure in the third week after ovulation increased IL-6 and TNF-α. In CREPL, single-day lag effect significantly increased IL-1ß (at lag 1), IL-6 (at lag 8), and TNF-α (at lag 5); distributed lag effect increased IL-6 (at lag 4-lag 8) and TNF-α (at lag 4-lag 6); and cumulative effect within ten days before villus collection increased IL-6. There was no statistically significant cumulative effect in NEP. In summary, maternal PM2.5 exposure was associated with placental inflammation in human early pregnancy, particularly with increased villus IL-6 in CREPL. Whether maternal-fetal interface inflammation related to PM2.5 exposure during the periovulatory period or later contributes to CREPL or other adverse pregnancy outcomes requires further study.

Ambient PM2.5 exposures and systemic inflammation in women with early pregnancy.

The association between ambient fine particulate matter (PM2.5) and systemic inflammation in women with early pregnancy is unclear. This study estimated the effects of PM2.5 exposures on inflammatory biomarkers in women with normal early pregnancy (NEP) or clinically recognized early pregnancy loss (CREPL). Serum interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured in 228 early pregnant women recruited in Tianjin, China. Maternal PM2.5 exposures at lag 0 through lag 30 before blood collection were estimated using temporally-adjusted land use regression models. Daily exposures to ambient PM10, NO2, SO2, CO and 8-hours maximum ozone were estimated using city-level concentrations. Single-day lag effects at lag 0 through lag 7 were estimated using multivariable linear regression models. Distributed lag effects and cumulative effects over the preceding seven days and 30 days were estimated using distributed lag non-linear models. Serum IL-1ß (8.0% increase at lag 3), IL-6 (33.9% increase at lag 5) and TNF-α (12.7% increase at lag 5) in early pregnant women were significantly increased with an interquartile range increase in PM2.5 exposures adjusted for temporal confounders and demographic characteristics. These effects were robust in several two-pollutant models. Distributed lag effects over the preceding 30 days also showed that the three cytokines were significantly increased with PM2.5 on some lag days. Among all cumulative effects of PM2.5 on the three cytokines in all subjects or in the two groups, only IL-6 was significantly increased in CREPL women over the preceding seven days and 30 days. No significant cumulative effect of PM2.5 was observed in NEP women. In conclusion, exposure to ambient PM2.5 may induce systemic inflammation in women in the first trimester of pregnancy. Whether the PM2.5-related cumulative increase in maternal IL-6 is involved in the pathogenic mechanisms of early pregnancy loss needs to be identified in future research.

LVFFARK-PEG-Stabilized Black Phosphorus Nanosheets Potently Inhibit Amyloid-ß Fibrillogenesis.

Deposition of amyloid-ß (Aß) aggregates in the brain is a main pathological hallmark of Alzheimer's disease (AD), so inhibition of Aß aggregation has been considered as a promising strategy for AD prevention and treatment. Black phosphorus (BP) is a 2D nanomaterial with high biocompatibility and unique biodegradability, but its potential application in biomedicine suffers from the rapid degradability and unfunctionability. To overcome the drawbacks and broaden its application, we have herein designed an Aß inhibitor (LK7)-coupled and polyethylene glycol (PEG)-stabilized BP-based nanosystem. The PEGylated-LK7-BP nanosheets (PEG-LK7@BP) not only exhibited a good stability but also demonstrated a significantly enhanced inhibitory potency on Aß42 fibrillogenesis in comparison with its counterparts. This elaborately designed PEG-LK7@BP stopped the conformational transition and suppressed the fibrillization of Aß42, so it could completely rescue cultured cells from the toxicity of Aß42 (by increasing the cell viability from 72 to 100%) at 100 µg/mL. It is considered that PEG-LK7@BP could bind Aß species by enhanced electrostatic and hydrophobic interactions and thus efficiently alleviated Aß-Aß interactions. Meanwhile, the coupled LK7 on the BP surface formed a high local concentration that enhanced the affinity between the nanosystem and Aß species. Finally, PEG could improve the stability and dispersibility of the nanoplatform to make it show an increased inhibitory effect on the amyloid formation. Hence, this work proved that PEG-LK7@BP is a promising nanosystem for the development of amyloid inhibitors fighting against AD.

Attitudes Toward Advance Directives Among Patients and Their Family Members in China.

OBJECTIVES: Chinese people are generally unfamiliar with the concept of advance care planning or advance directives (ACP/ADs), which raises dilemmas in life-support choice and can even affect clinical decision making. To understand and address the issues involved better, we investigated the awareness of ACP/ADs in China, as well as people's attitudes toward medical autonomy and end-of-life care. DESIGN: A multicenter cross-sectional survey, conducted from August 1 to December 31, 2016. SETTING: Twenty-five hospitals located in 15 different provinces throughout mainland China. PARTICIPANTS: Pairs of adult patients without dementia or malignancies, and a family member. MEASUREMENTS: Participants self-filled anonymous questionnaires, and the data collected were analyzed to relate patients' sociodemographic characteristics to their awareness of ACP/ADs and attitudes to health care autonomy and end-of-life care. RESULTS: Among 1084 patients who completed the questionnaire, 415 (38.3%) had heard about ACP/ADs. Having been informed about ACP/ADs, 995 (91.8%) were willing to find out their true health status and decide for themselves; 549 (50.6%) wanted to institute ACP/ADs. Regarding end-of-life care, 473 (43.6%) chose Do Not Resuscitate, and 435 (40.1%) wished to forgo life-support treatment if irreversibly moribund. Patients predominantly (481, 44.4%) chose general hospital as their preferred place to spend their last days of life; only 114 (10.5%) favored a special hospice facility. Patients' main concerns during end-of-life care were symptom control (35.1%), followed by functional maintenance and quality of life (29.8%), and prolonging life (18.9%). More highly educated patients had significantly greater awareness of ACP/ADs than less well educated ones (χ2 = 59.22, P < .001) and were more willing to find out the truth for themselves (χ2 = 58.30, P ≤ .001) and make medical decisions in advance (χ2 = 55.92, P < .001). Younger patients were also more willing than older ones to know the truth (χ2 = 38.23, P = .001) and make medical decisions in advance (χ2 = 18.42, P = .018), and were also more likely to wish to die at home (χ2 = 96.25, P < .001). Only 212 patients' family members (19.6%) wanted life-support treatment for themselves if irreversibly moribund, whereas 592 (54.6%) would want their relative to receive such procedures in the same circumstances; a similar discrepancy was evident for end-of-life invasive treatment (18.3% vs 42.7%). CONCLUSIONS: Awareness about ACP/ADs in China is still low. Providing culturally sensitive knowledge, education, and communication regarding ACP/ADs is a feasible first step to promoting this sociomedical practice.

Air quality, health, and climate implications of China's synthetic natural gas development.

Facing severe air pollution and growing dependence on natural gas imports, the Chinese government plans to increase coal-based synthetic natural gas (SNG) production. Although displacement of coal with SNG benefits air quality, it increases CO2 emissions. Due to variations in air pollutant and CO2 emission factors and energy efficiencies across sectors, coal replacement with SNG results in varying degrees of air quality benefits and climate penalties. We estimate air quality, human health, and climate impacts of SNG substitution strategies in 2020. Using all production of SNG in the residential sector results in an annual decrease of ∼32,000 (20,000 to 41,000) outdoor-air-pollution-associated premature deaths, with ranges determined by the low and high estimates of the health risks. If changes in indoor/household air pollution were also included, the decrease would be far larger. SNG deployment in the residential sector results in nearly 10 and 60 times greater reduction in premature mortality than if it is deployed in the industrial or power sectors, respectively. Due to inefficiencies in current household coal use, utilization of SNG in the residential sector results in only 20 to 30% of the carbon penalty compared with using it in the industrial or power sectors. Even if carbon capture and storage is used in SNG production with today's technology, SNG emits 22 to 40% more CO2 than the same amount of conventional gas. Among the SNG deployment strategies we evaluate, allocating currently planned SNG to households provides the largest air quality and health benefits with the smallest carbon penalties.