Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40–48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13–20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10−8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid‐β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti‐necroptotic molecule necrostatin‐1 (Nec‐1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double‐transgenic mice, Nec‐1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec‐1 against AD provide evidence that Nec‐1 may serve an important role in the development of preventive approach for AD.

Ternary blend approaches are demonstrated as a universal means to improve overall performance of organic photovoltaics (OPVs) in both indoor and outdoor conditions. A comparative study on two donors:one acceptor (2D:1A) and one donor:two acceptors (1D:2A) ternary blends shows that both approaches are universally effective for indoor and outdoor operation; the 1D:2A devices incorporating a nonfullerene acceptor (NFA) benefit from less charge recombination and higher power conversion efficiencies (PCEs) for various irradiation conditions, while the performance of the 2D:1A blends depends on the emission spectrum of the incident light source. The synergistic merits of NFAs and ternary structure in the 1D:2A ternary OPVs secure better performance and generality regardless of the incident lighting. A combination of experimental and theoretical analyses unveils that NFAs optimize packing and arrangement of molecules to build efficient cascade ternary junctions in the 1D:2A blends, which can be important design guidelines for the third component in ternary OPVs. The optimized 1D:2A ternary OPV exhibits a new record PCE of 25.6% under a 200 lux light‐emitting diode (LED) and 26.4% under a 1000 lux LED, and superior durability under industrial relevant thermal stress, suggesting new opportunities in diverse practical applications challenging the currently dominant PV technologies.

Understanding on effects of Pt size and oxygen vacancy at CeO2 surface in Pt/CeO2 catalyst for CO oxidation reaction enables to boost catalytic activity.

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Single-atom catalysts provide unique catalytic properties and maximize atom utilization efficiency. While utilizing them at elevated temperatures is highly desirable, their operating temperature is usually kept below 300°C to prevent...

Genetic variation in response to the environment, that is, genotype-by-environment interaction (GxE), is fundamental in the biology of complex traits and diseases. However, existing methods are computationally demanding and infeasible to handle biobank-scale data. Here, we introduce GxEsum, a method for estimating the phenotypic variance explained by genome-wide GxE based on GWAS summary statistics. Through comprehensive simulations and analysis of UK Biobank with 288,837 individuals, we show that GxEsum can handle a large-scale biobank dataset with controlled type I error rates and unbiased GxE estimates, and its computational efficiency can be hundreds of times higher than existing GxE methods.

Rhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed of dimethylcyclodecatriene flanked by a 7membered and a 6-membered lactone ring based on spectroscopic analysis. During an unbiased screening of natural product libraries, this novel compound was found to dissociate amyloid-b (Ab) plaques and tau tangles, which are key pathological hallmarks of Alzheimers disease (AD). Rhizolutin treatment of APP/PS1 double transgenic mice with AD significantly dissociated hippocampal plaques. In vitro, rhizolutin substantially decreased Ab-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce a unique chemical entity that targets Ab and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials.