Deletion variants calling in third-generation sequencing data based on a dual-attention mechanism.

Deletion is a crucial type of genomic structural variation and is associated with numerous genetic diseases. The advent of third-generation sequencing technology has facilitated the analysis of complex genomic structures and the elucidation of the mechanisms underlying phenotypic changes and disease onset due to genomic variants. Importantly, it has introduced innovative perspectives for deletion variants calling. Here we propose a method named Dual Attention Structural Variation (DASV) to analyze deletion structural variations in sequencing data. DASV converts gene alignment information into images and integrates them with genomic sequencing data through a dual attention mechanism. Subsequently, it employs a multi-scale network to precisely identify deletion regions. Compared with four widely used genome structural variation calling tools: cuteSV, SVIM, Sniffles and PBSV, the results demonstrate that DASV consistently achieves a balance between precision and recall, enhancing the F1 score across various datasets. The source code is available at https://github.com/deconvolution-w/DASV.

Telo boxes within the AGAMOUS second intron recruit histone 3 lysine 27 methylation to increase petal number in rose (Rosa chinensis) in response to low temperatures.

The petals of rose (Rosa sp.) flowers determine the ornamental and industrial worth of this species. The number of petals in roses was previously shown to be subject to fluctuations in ambient temperature. However, the mechanisms by which rose detects and responds to temperature changes are not entirely understood. In this study, we identified short interstitial telomere motifs (telo boxes) in the second intron of AGAMOUS (RcAG) from China rose (Rosa chinensis) that play an essential role in precise temperature perception. The second intron of RcAG harbors two telo boxes that recruit telomere repeat binding factors (RcTRBs), which interact with CURLY LEAF (RcCLF) to compose a repressor complex. We show that this complex suppresses RcAG expression when plants are subjected to low temperatures via depositing H3K27me3 marks (trimethylation of lysine 27 on histone H3) over the RcAG gene body. This regulatory mechanism explains the low-temperature-dependent decrease in RcAG transcript levels, leading to the production of more petals under these conditions. Our results underscore an interesting intron-mediated regulatory mechanism governing RcAG expression, enabling rose plants to perceive temperature cues and establish petal numbers.

5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes.

5-methylcytosine (m5C) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if m5C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m5C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (Plasmodium yoelii) and human (Plasmodium falciparum) malaria parasites. While different representations of m5C-modified mRNAs are associated with the different stages, the abundance of the m5C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m5C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Upon knockout of P. yoelii nsun2 (pynsun2), marked reductions of m5C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in the knockout rodent malaria parasites. Restoration of the nsun2 gene in the knockout parasites rescued the gametocyte production phenotype as well as m5C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m5C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.

Clinical characteristics and outcomes of liver transplant recipients infected by Omicron during the opening up of the dynamic zero-coronavirus disease policy in China: A prospective, observational study.

We analyzed the characteristics, risk factors, outcomes, and post-coronavirus disease 2019 (COVID-19) symptoms in liver transplant recipients in China's late 2022 COVID-19 wave. Recipients with COVID-19 were enrolled from December 1, 2022, to January 31, 2023, and followed up until May 31, 2023. Baseline and characteristic data were collected. A total of 930 recipients were included, with a vaccination rate (non-mRNA) of 40.0%. Among 726 (78.1%) recipients with COVID-19, 641 (88.3%) patients were treated at home, 81 (11.2%) patients required hospitalization in general wards, 4 (0.6%) patients required intensive care, and 1 (0.1%) patient died because of COVID-19. Severe acute respiratory syndrome coronavirus 2 infection was related to close contact with confirmed cases (P < .001) and the condition of end-stage kidney disease (P < .046). Older age, male sex, less vaccination, and hypertension were independent risk factors for hospitalization. Fatigue (36.9%) was the most common symptom post-COVID-19, followed by memory loss (35.7%) and sleep disturbance (23.9%). Two doses of vaccines had a protective effect against these post-COVID-19 symptoms (P < .05). During this Omicron outbreak, liver transplant recipients were susceptible to COVID-19, with frequent hospitalization but low mortality. Two doses of non-mRNA COVID-19 vaccines could protect against liver transplant recipient hospitalization and post-COVID-19 symptoms.

DeepTTA: a transformer-based model for predicting cancer drug response.

Identifying new lead molecules to treat cancer requires more than a decade of dedicated effort. Before selected drug candidates are used in the clinic, their anti-cancer activity is generally validated by in vitro cellular experiments. Therefore, accurate prediction of cancer drug response is a critical and challenging task for anti-cancer drugs design and precision medicine. With the development of pharmacogenomics, the combination of efficient drug feature extraction methods and omics data has made it possible to use computational models to assist in drug response prediction. In this study, we propose DeepTTA, a novel end-to-end deep learning model that utilizes transformer for drug representation learning and a multilayer neural network for transcriptomic data prediction of the anti-cancer drug responses. Specifically, DeepTTA uses transcriptomic gene expression data and chemical substructures of drugs for drug response prediction. Compared to existing methods, DeepTTA achieved higher performance in terms of root mean square error, Pearson correlation coefficient and Spearman's rank correlation coefficient on multiple test sets. Moreover, we discovered that anti-cancer drugs bortezomib and dactinomycin provide a potential therapeutic option with multiple clinical indications. With its excellent performance, DeepTTA is expected to be an effective method in cancer drug design.

preMLI: a pre-trained method to uncover microRNA-lncRNA potential interactions.

The interaction between microribonucleic acid and long non-coding ribonucleic acid plays a very important role in biological processes, and the prediction of the one is of great significance to the study of its mechanism of action. Due to the limitations of traditional biological experiment methods, more and more computational methods are applied to this field. However, the existing methods often have problems, such as inadequate acquisition of potential features of the sequence due to simple coding and the need to manually extract features as input. We propose a deep learning model, preMLI, based on rna2vec pre-training and deep feature mining mechanism. We use rna2vec to train the ribonucleic acid (RNA) dataset and to obtain the RNA word vector representation and then mine the RNA sequence features separately and finally concatenate the two feature vectors as the input of the prediction task. The preMLI performs better than existing methods on benchmark datasets and has cross-species prediction capabilities. Experiments show that both pre-training and deep feature mining mechanisms have a positive impact on the prediction performance of the model. To be more specific, pre-training can provide more accurate word vector representations. The deep feature mining mechanism also improves the prediction performance of the model. Meanwhile, The preMLI only needs RNA sequence as the input of the model and has better cross-species prediction performance than the most advanced prediction models, which have reference value for related research.

Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development.

Heterochromatin-associated gene silencing controls multiple physiological processes in malaria parasites, however, little is known concerning the regulatory network and cis-acting sequences involved in the organization of heterochromatin and how they modulate heterochromatic gene expression. Based on systematic profiling of genome-wide occupancy of eighteen Apicomplexan AP2 transcription factors by ChIP-seq analysis, we identify and characterize eight heterochromatin-associated factors (PfAP2-HFs), which exhibit preferential enrichment within heterochromatic regions but with differential coverage profiles. Although these ApiAP2s target euchromatic gene loci via specific DNA motifs, they are likely integral components of heterochromatin independent of DNA motif recognition. Systematic knockout screenings of ApiAP2 factors coupled with RNA-seq transcriptomic profiling revealed three activators and three repressors of heterochromatic gene expression including four PfAP2-HFs. Notably, expression of virulence genes is either completely silenced or significantly reduced upon the depletion of PfAP2-HC. Integrated multi-omics analyses reveal autoregulation and feed-forward loops to be common features of the ApiAP2 regulatory network, in addition to the occurrence of dynamic interplay between local chromatin structure and ApiAP2s in transcriptional control. Collectively, this study provides a valuable resource describing the genome-wide landscape of the ApiAP2 family and insights into functional divergence and cooperation within this family during the blood-stage development of malaria parasites.

Tetrazine-Isonitrile Bioorthogonal Fluorogenic Reactions Enable Multiplex Labeling and Wash-Free Bioimaging of Live Cells.

Developing fluorogenic probes for simultaneous live cell labeling of multiple targets is crucial for understanding complex cellular events. The emerging [4+1] cycloaddition between tetrazine and isonitriles holds promise as a bioorthogonal tool, yet existing tetrazine probes lack reactivity and fluorogenicity. Here, we present the development of a series of tetrazine-functionalized bioorthogonal probes. By incorporating pyrazole adducts into the fluorophore scaffolds, the post-reacted probes displayed remarkable fluorescence turn-on ratios, up to 3184-fold. Moreover, these modifications are generalizable to various fluorophores, enabling a broad emission range from 473 to 659 nm. Quantum chemical calculations further elucidate the turn-on mechanisms. These probes enable the simultaneous labeling of multiple targets in live cells, without the need for a washing step. Consequently, our findings pave the way for advanced multiplex imaging and detection techniques for cellular studies.

CRISPRi-microfluidics screening enables genome-scale target identification for high-titer protein production and secretion.

Genome-scale target identification promises to guide microbial cell factory engineering for higher-titer production of biomolecules such as recombinant proteins (r-protein), but challenges remain due to the need not only for comprehensive genotypic perturbation but also in conjunction with high-throughput phenotypic screening strategies. Here, we developed a CRISPRi-microfluidics screening platform to systematically identify crucial gene targets that can be engineered to enhance r-protein secretion in Corynebacterium glutamicum. We created a CRISPR interference (CRISPRi) library containing 46,549 single-guide RNAs, where we aimed to unbiasedly target all genes for repression. Meanwhile, we developed a highly efficient droplet-based microfluidics system integrating the FlAsH-tetracysteine assay that enables screening of millions of strains to identify potential knockdowns conducive to nanobody VHH secretion. Among our highest-ranking candidates are a slew of previously unknown targets involved in transmembrane transport, amino-acid metabolism and redox regulation. Guided by these findings, we eventually constructed a hyperproducer for multiple proteins via combinatorial engineering of redox-response transcription factors. As the near-universal applicability of CRISPRi technology and the FlAsH-based screening platform, this procedure might be expanded to include a varied variety of microbial species and recombinant proteins.

A systematic review and meta-analysis of primary bypass surgery compared with bypass surgery after endovascular treatment in peripheral artery disease patients.

OBJECTIVE: Both bypass surgery and endovascular treatment are well-recognized interventions for the treatment of peripheral artery disease; however, the effect of failed endovascular treatment on subsequent surgeries remains controversial. A systematic review was conducted to compare the outcomes of primary bypass and bypass surgery after endovascular treatment. METHODS: Three academic databases (Embase, PubMed, and Scopus) were searched from their inception to August 2022. Two independent investigators searched for studies that reported the outcomes of primary bypass surgery and bypass surgery after endovascular treatment in patients with peripheral artery disease. Abstracts and full-text studies were screened independently using duplicate data abstraction. Dichotomous outcome measures were reported using a random-effects model to generate a summary odds ratio (OR) and 95% confidence interval (CI). The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Seventeen retrospective observational studies were selected from 3911 articles and included 8064 patients, 6252 of whom underwent primary bypass surgery and 1812 underwent bypass surgery after endovascular treatment. The mean age was 69.0 years and 61.2% (n = 4938) were male. For perioperative outcomes, the 30-day results showed no difference in mortality (OR, 0.76; 95% CI, 0.53-1.10), or amputation (OR, 0.89; 95% CI, 0.67-1.20). For short- to mid-term outcomes, primary patency did not differ at 6 months (OR, 0.98; 95% CI, 0.81-1.19), 1 year (OR, 1.12; 95% CI, 0.97-1.30), or 2 years (OR, 1.17; 95% CI, 0.85-1.61) follow-up. Amputation-free survival did not differ at 6 months (OR, 1.03; 95% CI, 0.82-1.30), 1 year (OR, 1.09; 95% CI, 0.89-1.32), 2 years (OR, 1.18; 95% CI, 0.93-1.50), or 3 years (OR, 1.09; 95% CI, 0.84-1.40) of follow-up. No significant difference was found in overall survival or second patency. CONCLUSIONS: This meta-analysis of retrospective, nonrandomized, observational studies suggests that prior endovascular treatment of lower extremity arterial disease does not result in worse perioperative, short-term, or mid-term clinical outcomes of subsequent infrainguinal bypass surgery compared with patients without prior endovascular treatment.

Effects of ambient air pollution on outpatient visits for psoriasis in Wuhan, China: a time-series analysis.

BACKGROUND: Psoriasis can be provoked by both external and internal factors. The effects of environmental factors on psoriasis remain unclear. OBJECTIVES: To investigate the effects of air pollution on outpatient visits for psoriasis. METHODS: A distributed lag nonlinear model following quasi-Poisson regression was used to evaluate the lag effects of air pollutants on psoriasis outpatient visits, adjusting for potential confounders. Stratified analyses were performed to identify potential effect modifications by sex, age and season. RESULTS: In total, 13 536 outpatient visits for psoriasis were recorded in Wuhan, China from 1 January 2015 to 31 December 2019. In the single-pollutant model, exposures to particulate matter (PM) smaller than 2.5 µm (PM2.5), PM smaller than 10 µm (PM10), NO2 and SO2 were found to be significantly associated with increased daily psoriasis outpatient visits. For the largest effects, a 10-µg m-3 increase in concentrations of PM2.5 (lag1), PM10 (lag1), NO2 (lag0) and SO2 (lag3) corresponded to 0.32% [95% confidence interval (CI) 0.01-0.63], 0.26% (95% CI 0.05-0.48), 0.98% (95% CI 0.01-1.96) and 2.73% (95% CI 1.01-4.47) increases in psoriasis outpatient visits, respectively. In the two-pollutant model, only NO2 showed significant and stable effects on the outpatient visits for psoriasis. CONCLUSIONS: Ambient air pollution, especially NO2, appears to be significantly associated with an increased risk of outpatient visits for psoriasis in Wuhan, China. Air pollution control and exposure prevention could be effective measures to relieve the symptoms of psoriasis among these patients.

A clinical study on microwave ablation of multifocal (≤ 3) T1N0M0 papillary thyroid carcinoma.

OBJECTIVE: To evaluate the feasibility, efficiency, and safety of microwave ablation (MWA) for T1N0M0 multifocal (≤ 3) papillary thyroid carcinoma (PTC). METHODS: This was a retrospective study, and patients who underwent MWA for multifocal (≤ 3) PTC were reviewed between October 2016 and December 2020. After ablation, the changes in tumor size and volume, as well as the rate of technical success, tumor disappearance, disease progression, and complications were assessed. RESULTS: There were a total of 57 cases enrolled in the present study, which included 18 males and 39 females. The mean age was 44 ± 11 years (22-66 years); the mean follow-up time was 18 ± 11 months (6-48 months). Complete ablation was achieved in all enrolled cases. Therefore, the technical success rate was 100%. Due to expanding ablation, the MD and volume of the ablation zone, as well as the VRR, increased at the 1st and 3rd months after ablation and decreased at 12 and 18 months after ablation (p < 0.05 for all). The total complete tumor disappearance rate was 43.9% (25/57), including 54% (24/44) in the T1a subgroup vs. 7.7% (1/13) in the T1b subgroup (p = 0.003). The total disease progression rate was 7% (4/57), including 9.1% (4/44) in the T1a subgroup vs. 0% (0/13) in the T1b subgroup (p = 0.142). The overall complication rate was 5.3% (3/57), including 6.8% (4/44) in the T1a subgroup vs. 0% (0/13) in the T1b subgroup (p = 0.206). CONCLUSION: This preliminary study indicates that MWA is a safe and effective treatment for T1N0M0 multifocal (≤ 3) PTC. KEY POINTS: • MWA is a promising alternative method for T1N0M0 multifocal (≤ 3) PTC.

Preliminary Study of Microwave Ablation for Multifocal Papillary Thyroid Microcarcinoma in Nonoperative Candidates.

PURPOSE: To study the feasibility, safety, and effectiveness of microwave ablation (MWA) in patients with multifocal papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: This retrospective study included patients who underwent MWA for multifocal PTMC (number of nodules ≤3). A total of 44 patients were included, and the mean age was 43 years (SD ± 11). After ablation, progression-free survival (PFS) at 6, 12, 24, 36, and 48 months; disease progression; change in tumor size and volume; tumor disappearance rate; and adverse events (AEs) were assessed, and the feasibility, safety, and effectiveness of MWA for PTMC were evaluated on the basis of statistical analysis. RESULTS: The median follow-up period was 18 months (interquartile range, 12-33 months). The PFS rates at 6, 12, 24, 36, and 48 months were 100.0%, 96.4%, 96.4%, 70.3%, and 52.7%, respectively. The disease progression rate was 11.4% (5 of 44 patients). The maximum diameter (MD) and volume of the ablation zone were larger at the 3-month follow-up than before ablation (median MD, 13.0 vs 7.0 mm; P < .001; median volume, 503.8 vs 113.0 mm3; P < .001). Subsequently, the tumors exhibited a reduction in both size and volume after 18 months (median MD, 4.0 vs 7.0 mm; P = .04; median volume, 12.6 vs 113.0 mm3; P = .055). At the end of the follow-up period, the complete response rate was 59% (26 of 44 patients). The overall AE rate was 6.8%. CONCLUSIONS: MWA is a feasible treatment for PTMC (number of nodules ≤3), and this study preliminarily demonstrated the safety and effectiveness of this technique.

A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum.

Gametocytogenesis, the process by which malaria parasites produce sexual forms that can infect mosquitoes, is essential for the transmission of malaria. A transcriptional switch of the pfap2-g gene triggers sexual commitment, but how the complex multi-step process is precisely programed remains largely unknown. Here, by systematic functional screening of a panel of ApiAP2 transcription factors, we identify six new ApiAP2 members associated with gametocytogenesis in Plasmodium falciparum. Among these, PfAP2-G5 (PF3D7_1139300) was found to be indispensable for gametocytogenesis. This factor suppresses the transcriptional activity of the pfap2-g gene via binding to both the upstream region and exonic gene body, the latter is linked to the maintenance of local heterochromatin structure, thereby preventing initiation of sexual commitment. Removal of this repressive effect through pfap2-g5 knockout disrupts the asexual replication cycle and promotes sexual commitment accompanied by upregulation of pfap2-g expression. However, the gametocytes produced fail to mature fully. Further analyses show that PfAP2-G5 is essential for gametocyte maturation, and causes the down-regulation of pfap2-g and a set of early gametocyte genes activated by PfAP2-G prior to gametocyte development. Collectively, our findings reveal a regulation cascade of gametocyte production in malaria parasites, and provide a new target for transmission blocking interventions.

ATAD3A gene variations in a family with Harel-Yoon syndrome. / Harel-Yoon综合征一家系临床表型及ATAD3AåŸºå› å˜å¼‚åˆ†æž.

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.

CircRNA-SCAF8 promotes vascular endothelial cell pyroptosis by regulating the miR-93-5p/TXNIP axis. / 环状RNA-SCAF8通过miR-93-5p/TXNIPé€šè·¯ä¿ƒè¿›è¡€ç®¡å† çš®ç»†èƒžç„¦äº¡.

OBJECTIVES: To investigate the role and mechanism of circRNA-SR-related CTD associated factor 8 (SCAF8) in regulating endothelial cell pyroptosis in high glucose environment. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into six groups. The normal control group and high glucose control group were cultured in cell culture medium with 5 and 33 mmol/L glucose, respectively. The RNA control group, circRNA-SCAF8 inhibition group, miR-93-5p overexpression group and miR-93-5p inhibition group were added with non-functional siRNA, circRNA-SCAF8 inhibitor, miR-93-5p overexpression molecule and miR-93-5p inhibitor in high glucose environment, respectively. Cell viability and pyroptosis were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and Hoechst 33342/propidium iodide fluorescence double staining. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of pyroptosis-related factors including apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartic acid specific protease-1 (caspase-1) and Gasdermin D (GSDMD), NOD like receptor protein 3 (NLRP-3), thioredoxin interacting proteins (TXNIP), IL-18 and IL-1ß. The expression of circRNA-SCAF8, miR-93-5p and TXNIP was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to locate circRNA-SCAF8 and miR-93-5p. Dual luciferase assay was used to verify the targeted regulatory relationship between miR-93-5p and upstream and downstream molecules. RESULTS: Compared with the RNA control group, the cell survival rate of circRNA-SCAF8 inhibition group and miR-93-5p overexpression group increased (both P<0.01), the pyroptosis decreased (both P<0.01), and the expressions of pyroptosis-related factors such as TXNIP, NLRP-3, caspase-1, GSDMD, ASC, IL-18 and IL-1ß were significantly decreased (all P<0.05). The expression of miR-93-5p was significantly increased after inhibition of circRNA-SCAF8 (P<0.01), and the expression of circRNA-SCAF8 tended to decrease after overexpression of miR-93-5p, but with no statistical significance (P>0.05). Dual luciferase assay showed that miR-93-5p downre-gulated circRNA-SCAF8 expression by binding to the 3 ´ UTR region of circRNA-SCAF8, and miR-93-5p downregulated TXNIP expression by binding to the 3 ´ UTR region of TXNIP. FISH showed that circRNA-SCAF8 and miR-93-5p were both located in the cytoplasm and were highly associated in the cells. qRT-PCR showed that the relative expression of TXNIP increased or decreased after overexpression or inhibition of miR-93-5p compared with the RNA control group, respectively (both P<0.05), suggesting that miR-93-5p could regulate TXNIP gene expression. CONCLUSIONS: CircRNA-SCAF8/miR-93-5p/TXNIP axis is involved in the regulation of pyroptosis in HUVECs under high glucose.

Green-solvent Processable Dopant-free Hole Transporting Materials for Inverted Perovskite Solar Cells.

The commercialization of perovskite solar cells (PVSCs) urgently requires the development of green-solvent processable dopant-free hole transporting materials (HTMs). However, strong intermolecular interactions that ensure high hole mobility always compromise the solubility and film-forming ability in green solvents. Herein, we show a simple but effective design strategy to solve this trade-off, that is, constructing star-shaped D-A-D structure. The resulting HTMs (BTP1-2) can be processed by green solvent of 2-methylanisole (2MA), a kind of food additive, and show high hole mobility and multiple defect passivation effects. An impressive efficiency of 24.34 % has been achieved for 2MA-processed BTP1 based inverted PVSCs, the highest value for green-solvent processable HTMs so far. Moreover, it is manifested that the charge separation of D-A type HTMs at the photoinduced excited state can help to passivate the defects of perovskites, indicating a new HTM design insight.

Enhanced Metal-Support Interactions Boost the Electrocatalytic Water Splitting of Supported Ruthenium Nanoparticles on a Ni3 N/NiO Heterojunction at Industrial Current Density.

Developing highly efficient and stable hydrogen production catalysts for electrochemical water splitting (EWS) at industrial current densities remains a great challenge. Herein, we proposed a heterostructure-induced-strategy to optimize the metal-support interaction (MSI) and the EWS activity of Ru-Ni3 N/NiO. Density functional theory (DFT) calculations firstly predicted that the Ni3 N/NiO-heterostructures can improve the structural stability, electronic distributions, and orbital coupling of Ru-Ni3 N/NiO compared to Ru-Ni3 N and Ru-NiO, which accordingly decreases energy barriers and increases the electroactivity for EWS. As a proof-of-concept, the Ru-Ni3 N/NiO catalyst with a 2D Ni3 N/NiO-heterostructures nanosheet array, uniformly dispersed Ru nanoparticles, and strong MSI, was successfully constructed in the experiment, which exhibited excellent HER and OER activity with overpotentials of 190 mV and 385 mV at 1000 mA cm-2 , respectively. Furthermore, the Ru-Ni3 N/NiO-based EWS device can realize an industrial current density (1000 mA cm-2 ) at 1.74 V and 1.80 V under alkaline pure water and seawater conditions, respectively. Additionally, it also achieves a high durability of 1000 h (@ 500 mA cm-2 ) in alkaline pure water.

Hyperhomocysteinemia Induces Rat Memory Impairment Via Injuring Hippocampal CA3 Neurons and Downregulating cAMP Response Element-Binding Protein (CREB) Phosphorylation.

Accumulated evidence demonstrated that an elevated plasma homocysteine level, hyperhomocysteinemia, induced cognitive impairment in animals, elderly and the patients with neurodegenerative diseases. To date, the underlying cellular and molecular mechanisms by which hyperhomocysteinemia induces cognitive impairment has not been clearly defined. The purpose of this study was to investigate the possible cellular and molecular mechanisms behind hyperhomocysteinemia signaling in rat memory impairment. The results from this study demonstrated that hyperhomocysteinemia induced neuronal damage and loss in hippocampal CA3 region and downregulated the cAMP response element-binding protein (CREB) phosphorylation. The findings of this study provide evidence that hyperhomocysteinemia induces rat memory impairment via injuring hippocampal CA3 neurons and downregulating CREB phosphorylation.

A New Diazabenzo[k]fluoranthene-Based D-A Conjugated Polymer Donor for Efficient Organic Solar Cells.

The development of wide-bandgap polymer donors having complementary absorption and compatible energy levels with near-infrared (NIR) absorbing nonfullerene acceptors is highly important for realizing high-performance organic solar cells (OSCs). Herein, a new thiophene-fused diazabenzo[k]fluoranthene derivative is successfully synthesized as the electron-deficient unit to construct an efficient donor-acceptor (D-A) type alternating copolymer donor, namely, PABF-Cl, using the chlorinated benzo[1,2-b:4,5-b']dithiophene as the copolymerization unit. PABF-Cl exhibits a wide optical bandgap of 1.93 eV, a deep highest occupied molecular level of -5.36 eV, and efficient hole transport. As a result, OSCs with the best power conversion efficiency of 11.8% are successfully obtained by using PABF-Cl as the donor to blend with a NIR absorbing BTP-eC9 acceptor. This work provides a new design of electron-deficient unit for constructing high-performance D-A type polymer donors.