Temporal alteration of serum bilirubin levels and its renoprotective effects in diabetic kidney disease: exploring the hormonal mechanisms.

Objective: This current study represents a novel endeavor to scrutinize the correlation between the temporal alteration in serum total bilirubin (TBIL) concentrations and the rate of estimated glomerular filtration rate (eGFR). Additionally, this study aims to probe the plausible molecular mechanism underpinning the renoprotective effects of bilirubin concerning its hormonal characteristics. Materials and methods: In this study, a cohort of 103 patients diagnosed with DKD and receiving medical care at Dongzhimen Hospital were recruited and monitored over a period of 2-7 years. The progression of DKD was ascertained using a threshold of eGFR decline > -5.48%/year. To assess the relationship between the annual change in serum TBIL levels (%/year) and the slope of eGFR, multivariate binary logistic regression analysis was employed. Furthermore, the ROC curve analysis was employed to determine the cut-off value for TBIL levels (%/year). Results: The use of multivariate binary logistic regression models revealed that serum TBIL levels (%/year) exhibited a significant correlation with the slope of eGFR. Moreover, the ROC curve analysis indicated a cut-off value of -6.729%/year for TBIL levels (%/year) with a sensitivity of 0.75 and specificity of 0.603, in diagnosing eGFR decline >-5.48%/year. Conclusions: The findings of this study suggest that the sustained elevation of serum bilirubin concentration within the physiological range can effectively retard the progression of Diabetic Kidney Disease (DKD). Furthermore, the hormonal attributes of bilirubin may underlie its renoprotective effects.

One-atom-thick hexagonal boron nitride co-catalyst for enhanced oxygen evolution reactions.

Developing efficient (co-)catalysts with optimized interfacial mass and charge transport properties is essential for enhanced oxygen evolution reaction (OER) via electrochemical water splitting. Here we report one-atom-thick hexagonal boron nitride (hBN) as an attractive co-catalyst with enhanced OER efficiency. Various electrocatalytic electrodes are encapsulated with centimeter-sized hBN films which are dense and impermeable so that only the hBN surfaces are directly exposed to reactive species. For example, hBN covered Ni-Fe (oxy)hydroxide anodes show an ultralow Tafel slope of ~30 mV dec-1 with improved reaction current by about 10 times, reaching ~2000 mA cm-2 (at an overpotential of ~490 mV) for over 150 h. The mass activity of hBN co-catalyst is found exceeding that of commercialized catalysts by up to five orders of magnitude. Using isotope experiments and simulations, we attribute the results to the adsorption of oxygen-containing intermediates at the insulating co-catalyst, where localized electrons facilitate the deprotonation processes at electrodes. Little impedance to electron transfer is observed from hBN film encapsulation due to its ultimate thickness. Therefore, our work also offers insights into mechanisms of interfacial reactions at the very first atomic layer of electrodes.

Patriotism, nationalism, and evaluations of the government's handling of the coronavirus crisis.

Introduction: The COVID-19 pandemic has been accompanied by a global rise of nationalism, and many countries' responses to the pandemic have further intensified nationalist sentiments. The public is polarized over government policies toward the pandemic. Hence, this study examined the associations of patriotism and nationalism with the support for lockdown policies and evaluations of governmental performance. Methods: We recruited 180 participants from one Chinese university. Results: Patriotism and nationalism had a direct effect on evaluations of governmental performance. Patriotism also had indirect effects on favorable evaluations of governmental performance through the support of lockdown policies. In addition, this study examined the relationship of threat perception and evaluations of governmental performance in the pandemic. Discussion: This relationship was found to be insignificant; however, the interaction effects between threat perception and patriotism on evaluations of governmental performance were significant. The implications of the study results are discussed.

Gas permeation through graphdiyne-based nanoporous membranes.

Nanoporous membranes based on two dimensional materials are predicted to provide highly selective gas transport in combination with extreme permeance. Here we investigate membranes made from multilayer graphdiyne, a graphene-like crystal with a larger unit cell. Despite being nearly a hundred of nanometers thick, the membranes allow fast, Knudsen-type permeation of light gases such as helium and hydrogen whereas heavy noble gases like xenon exhibit strongly suppressed flows. Using isotope and cryogenic temperature measurements, the seemingly conflicting characteristics are explained by a high density of straight-through holes (direct porosity of ∼0.1%), in which heavy atoms are adsorbed on the walls, partially blocking Knudsen flows. Our work offers important insights into intricate transport mechanisms playing a role at nanoscale.

An App-Based Workplace Mindfulness Intervention, and Its Effects Over Time.

We investigated the week-to-week effects of a mindfulness intervention on emotional exhaustion, work engagement, and job satisfaction in a field study involving 218 participants who participated and reported their weekly outcomes during the 8-week program. To examine how mindfulness impacted work outcomes, we used intraindividual modeling of the 8-week data. Mindfulness increased over time, and time also had indirect effects on emotional exhaustion, work engagement, and job satisfaction, through mindfulness. Supplementary growth curve analyses on the improvement of mindfulness over time showed a slight decrease in the positive effect of time on mindfulness.

Atomically thin photoanode of InSe/graphene heterostructure.

Achieving high-efficiency photoelectrochemical water splitting requires a better understanding of ion kinetics, e.g., diffusion, adsorption and reactions, near the photoelectrode's surface. However, with macroscopic three-dimensional electrodes, it is often difficult to disentangle the contributions of surface effects to the total photocurrent from that of various factors in the bulk. Here, we report a photoanode made from a InSe crystal monolayer that is encapsulated with monolayer graphene to ensure high stability. We choose InSe among other photoresponsive two-dimensional (2D) materials because of its unique properties of high mobility and strongly suppressing electron-hole pair recombination. Using the atomically thin electrodes, we obtained a photocurrent with a density >10 mA cm-2 at 1.23 V versus reversible hydrogen electrode, which is several orders of magnitude greater than other 2D photoelectrodes. In addition to the outstanding characteristics of InSe, we attribute the enhanced photocurrent to the strong coupling between the hydroxide ions and photo-generated holes near the anode surface. As a result, a persistent current even after illumination ceased was also observed due to the presence of ions trapped holes with suppressed electron-hole recombination. Our results provide atomically thin materials as a platform for investigating ion kinetics at the electrode surface and shed light on developing next-generation photoelectrodes with high efficiency.

Seamlessly Splicing Metallic Sn x Mo1- x S2 at MoS2 Edge for Enhanced Photoelectrocatalytic Performance in Microreactor.

Accurate design of the 2D metal-semiconductor (M-S) heterostructure via the covalent combination of appropriate metallic and semiconducting materials is urgently needed for fabricating high-performance nanodevices and enhancing catalytic performance. Hence, the lateral epitaxial growth of M-S Sn x Mo1- x S2/MoS2 heterostructure is precisely prepared with in situ growth of metallic Sn x Mo1- x S2 by doping Sn atoms at semiconductor MoS2 edge via one-step chemical vapor deposition. The atomically sharp interface of this heterostructure exhibits clearly distinguished performance based on a series of characterizations. The oxygen evolution photoelectrocatalytic performance of the epitaxial M-S heterostructure is 2.5 times higher than that of pure MoS2 in microreactor, attributed to the efficient electron-hole separation and rapid charge transfer. This growth method provides a general strategy for fabricating seamless M-S lateral heterostructures by controllable doping heteroatoms. The M-S heterostructures show increased carrier migration rate and eliminated Fermi level pinning effect, contributing to their potential in devices and catalytic system.

Stay Mindful and Carry on: Mindfulness Neutralizes COVID-19 Stressors on Work Engagement via Sleep Duration.

We examine whether mindfulness can neutralize the negative impact of COVID-19 stressors on employees' sleep duration and work engagement. In Study 1, we conducted a field experiment in Wuhan, China during the lockdown between February 20, 2020, and March 2, 2020, in which we induced state mindfulness by randomly assigning participants to either a daily mindfulness practice or a daily mind-wandering practice. Results showed that the sleep duration of participants in the mindfulness condition, compared with the control condition, was less impacted by COVID-19 stressors (i.e., the increase of infections in the community). In Study 2, in a 10-day daily diary study in the United Kingdom between June 8, 2020, and June 19, 2020, we replicate our results from Study 1 using a subjective measure of COVID-19 stressors and a daily measure of state mindfulness. In addition, we find that mindfulness buffers the negative effect of COVID-19 stressors on work engagement mediated by sleep duration. As the COVID-19 pandemic is ongoing and the number of reported cases continues to rise globally, our findings suggest that mindfulness is an evidence-based practice that can effectively neutralize the negative effect of COVID-19 stressors on sleep and work outcomes. The findings of the present study contribute to the employee stress and well-being literature as well as the emerging organizational research on mindfulness.

Association of prostate cancer risk with SNPs in regions containing androgen receptor binding sites captured by ChIP-On-chip analyses.

BACKGROUND: Genome-wide association studies (GWAS) have identified approximately three dozen single nucleotide polymorphisms (SNPs) consistently associated with prostate cancer (PCa) risk. Despite the reproducibility of these associations, the molecular mechanism for most of these SNPs has not been well elaborated as most lie within non-coding regions of the genome. Androgens play a key role in prostate carcinogenesis. Recently, using ChIP-on-chip technology, 22,447 androgen receptor (AR) binding sites have been mapped throughout the genome, greatly expanding the genomic regions potentially involved in androgen-mediated activity. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that sequence variants in AR binding sites are associated with PCa risk, we performed a systematic evaluation among two existing PCa GWAS cohorts; the Johns Hopkins Hospital and the Cancer Genetic Markers of Susceptibility (CGEMS) study population. We demonstrate that regions containing AR binding sites are significantly enriched for PCa risk-associated SNPs, that is, more than expected by chance alone. In addition, compared with the entire genome, these newly observed risk-associated SNPs in these regions are significantly more likely to overlap with established PCa risk-associated SNPs from previous GWAS. These results are consistent with our previous finding from a bioinformatics analysis that one-third of the 33 known PCa risk-associated SNPs discovered by GWAS are located in regions of the genome containing AR binding sites. CONCLUSIONS/SIGNIFICANCE: The results to date provide novel statistical evidence suggesting an androgen-mediated mechanism by which some PCa associated SNPs act to influence PCa risk. However, these results are hypothesis generating and ultimately warrant testing through in-depth molecular analyses.

Identification of conserved and novel microRNAs that are responsive to heat stress in Brassica rapa.

The species Brassica rapa includes various vegetable crops. Production of these vegetable crops is usually impaired by heat stress. Some microRNAs (miRNAs) in Arabidopsis have been considered to mediate gene silencing in plant response to abiotic stress. However, it remains unknown whether or what miRNAs play a role in heat resistance of B. rapa. To identify genomewide conserved and novel miRNAs that are responsive to heat stress in B. rapa, we defined temperature thresholds of non-heading Chinese cabbage (B. rapa ssp. chinensis) and constructed small RNA libraries from the seedlings that had been exposed to high temperature (46 °C) for 1 h. By deep sequencing and data analysis, we selected a series of conserved and novel miRNAs that responded to heat stress. In total, Chinese cabbage shares at least 35 conserved miRNA families with Arabidopsis thaliana. Among them, five miRNA families were responsive to heat stress. Northern hybridization and real-time PCR showed that the conserved miRNAs bra-miR398a and bra-miR398b were heat-inhibitive and guided heat response of their target gene, BracCSD1; and bra-miR156h and bra-miR156g were heat-induced and its putative target BracSPL2 was down-regulated. According to the criteria of miRNA and miRNA* that form a duplex, 21 novel miRNAs belonging to 19 miRNA families were predicted. Of these, four were identified to be heat-responsive by Northern blotting and/or expression analysis of the putative targets. The two novel miRNAs bra-miR1885b.3 and bra-miR5718 negatively regulated their putative target genes. 5'-Rapid amplification of cDNA ends PCR indicated that three novel miRNAs cleaved the transcripts of their target genes where their precursors may have evolved from. These results broaden our perspective on the important role of miRNA in plant responses to heat.

A genome-wide survey over the ChIP-on-chip identified androgen receptor-binding genomic regions identifies a novel prostate cancer susceptibility locus at 12q13.13.

BACKGROUND: The molecular mechanisms for the genome-wide association studies (GWAS)-identified prostate cancer (PCa) risk-associated single-nucleotide polymorphisms (SNP) remain largely unexplained. One recent finding that the PCa risk SNPs are enriched in genomic regions containing androgen receptor (AR)-binding sites has suggested altered AR signaling as a potentially important mechanism. METHODS: To explore novel associations by leveraging this knowledge, we utilized a meta-analysis previously done over SNPs harbored in ChIP-on-chip identified AR-binding genomic regions using the GWAS data from the Johns Hopkins Hospital (JHH) and the Cancer Genetic Markers of Susceptibility (CGEMS) study, and subsequently evaluated the top associations in a third population from the CAncer of the Prostate in Sweden (CAPS) study. RESULTS: One SNP (rs4919743: G>A), located at the KRT8 locus at 12q13.13 which encodes a keratin protein (K8) long used as a prostate epithelial malignancy marker and implicated in the tumorigenesis of several cancer types, was identified to be associated with PCa risk. The frequency of its minor "A" allele was consistently higher in PCa cases than in controls in all three study populations, with a combined OR of 1.22 (95% CI: 1.13-1.32) and an overall P value of 4.50 × 10(-7) (Bonferroni corrected, P = 0.006). CONCLUSION: We have identified a novel genetic locus that is associated with PCa risk. IMPACT: This study illustrated the great potential of prior biological knowledge in facilitating the search for novel disease-associated genetic loci. This finding warrants further replication in other studies.

A novel class of heat-responsive small RNAs derived from the chloroplast genome of Chinese cabbage (Brassica rapa).

BACKGROUND: Non-coding small RNAs play critical roles in various cellular processes in a wide spectrum of eukaryotic organisms. Their responses to abiotic stress have become a popular topic of economic and scientific importance in biological research. Several studies in recent years have reported a small number of non-coding small RNAs that map to chloroplast genomes. However, it remains uncertain whether small RNAs are generated from chloroplast genome and how they respond to environmental stress, such as high temperature. Chinese cabbage is an important vegetable crop, and heat stress usually causes great losses in yields and quality. Under heat stress, the leaves become etiolated due to the disruption and disassembly of chloroplasts. In an attempt to determine the heat-responsive small RNAs in chloroplast genome of Chinese cabbage, we carried out deep sequencing, using heat-treated samples, and analysed the proportion of small RNAs that were matched to chloroplast genome. RESULTS: Deep sequencing provided evidence that a novel subset of small RNAs were derived from the chloroplast genome of Chinese cabbage. The chloroplast small RNAs (csRNAs) include those derived from mRNA, rRNA, tRNA and intergenic RNA. The rRNA-derived csRNAs were preferentially located at the 3'-ends of the rRNAs, while the tRNA-derived csRNAs were mainly located at 5'-termini of the tRNAs. After heat treatment, the abundance of csRNAs decreased in seedlings, except those of 24 nt in length. The novel heat-responsive csRNAs and their locations in the chloroplast were verified by Northern blotting. The regulation of some csRNAs to the putative target genes were identified by real-time PCR. Our results reveal that high temperature suppresses the production of some csRNAs, which have potential roles in transcriptional or post-transcriptional regulation. CONCLUSIONS: In addition to nucleus, the chloroplast is another important organelle that generates a number of small RNAs. Many members of csRNA families are highly sensitive to heat stress. Some csRNAs respond to heat stress by silencing target genes. We suggest that proper temperature is important for production of chloroplast small RNAs, which are associated with plant resistance to abiotic stress.

Functional annotation of risk loci identified through genome-wide association studies for prostate cancer.

BACKGROUND: The majority of established prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association studies do not fall into protein coding regions. Therefore, the mechanisms by which these SNPs affect PCa risk remain unclear. Here, we used a series of bioinformatic tools and databases to provide possible molecular insights into the actions of risk SNPs. METHODOLOGY/PRINCIPAL FINDINGS: We performed a comprehensive assessment of the potential functional impact of 33 SNPs that were identified and confirmed as associated with PCa risk in previous studies. For these 33 SNPs and additional SNPs in linkage disequilibrium (LD) (r(2) ≥ 0.5), we first mapped them to genomic functional annotation databases, including the encyclopedia of DNA elements (ENCODE), 11 genomic regulatory elements databases defined by the University of California Santa Cruz (UCSC) table browser, and androgen receptor (AR)-binding sites defined by a ChIP-chip technique. Enrichment analysis was then carried out to assess whether the risk SNP blocks were enriched in the various annotation sets. Risk SNP blocks were significantly enriched over that expected by chance in two annotation sets, including AR-binding sites (P = 0.003), and FoxA1-binding sites (P = 0.05). About one-third of the 33 risk SNP blocks are located within AR-binding regions. CONCLUSIONS/SIGNIFICANCE: The significant enrichment of risk SNPs in AR-binding sites may suggest a potential molecular mechanism for these SNPs in PCa initiation, and provide guidance for future functional studies.