Non-syndromic cleft lip with palate (NSCLP) is the most serious sub-phenotype of non-syndromic orofacial clefts (NSOFC), which are the most common craniofacial birth defects in humans. Here we conduct a GWAS of NSCLP with multiple independent replications, totalling 7,404 NSOFC cases and 16,059 controls from several ethnicities, to identify new NSCLP risk loci, and explore the genetic heterogeneity between sub-phenotypes of NSOFC. We identify 41 SNPs within 26 loci that achieve genome-wide significance, 14 of which are novel (RAD54B, TMEM19, KRT18, WNT9B, GSC/DICER1, PTCH1, RPS26, OFCC1/TFAP2A, TAF1B, FGF10, MSX1, LINC00640, FGFR1 and SPRY1). These 26 loci collectively account for 10.94% of the heritability for NSCLP in Chinese population. We find evidence of genetic heterogeneity between the sub-phenotypes of NSOFC and among different populations. This study substantially increases the number of genetic susceptibility loci for NSCLP and provides important insights into the genetic aetiology of this common craniofacial malformation.

Single or few-layered MoS nanosheets, as a novel class of 2D nanomaterials, have received tremendous attention due to their fantastic physical and chemical properties. Here, we fabricated MoS-PEG-CpG with a small and uniform size as a multifunctional platform for photothermal enhanced immunotherapy. MoS nanosheets were fabricated by chemical exfoliation and further probe sonication. To realize MoS-based adjuvant delivery, MoS nanosheets were functionalized with cytosine-phosphate-guanine (CpG) and polyethylene glycol (PEG) to form MoS-PEG-CpG nanoconjugates. As an efficient nanocarrier with excellent near infrared-light (NIR) absorbing performance, MoS-PEG-CpG significantly promotes CpG intracellular accumulation and the effect can be further enhanced by photothermal treatment. In addition, the enhanced uptake can stimulate the production of proinflammatory cytokines and remarkably elevate the immune response level. Finally, we found that MoS-PEG-CpG could reduce the proliferative activity of cancer cells when co-cultured with a macrophage-like cell upon NIR irradiation, implying a novel strategy for multifunctional therapeutics against cancers.

The complex pathogenic mechanisms of Alzheimer's disease (AD) include the aggregation of β-amyloid peptides (Aβ) into oligomers or fibrils as well as Aβ-mediated oxidative stress, which require comprehensive treatment. Therefore, the inhibition of Aβ aggregation and free-radical scavenging are essential for the treatment of AD. Nanoparticles (NPs) have been found to influence Aβ aggregation process in vitro. Herein, we report the inhibition effects of molybdenum disulfide (MoS) NPs on Aβ aggregation. Polyvinylpyrrolidone-functionalized MoS NPs were fabricated by a pulsed laser ablation method. We find that MoS NPs exhibit multifunctional effects on Aβ peptides: inhibiting Aβ aggregation, destabilizing Aβ fibrils, alleviating Aβ-induced oxidative stress, as well as Aβ-mediated cell toxicity. Moreover, we show that MoS NPs can block the formation of the Ca channel induced by Aβ fibrils in the cell membrane for the first time. Thus, these observations suggest that MoS NPs have great potential for a multifunctional therapeutic agent against amyloid-related diseases.

Complicated vessels pervade almost all body tissues and influence the pathophysiology of the human body significantly. However, current fabrication strategies have limited success at multiscale vascular biofabrication. This study reports a methodology to fabricate soft vascularized tissue at centimeter scale using multimaterial bioprinting by a customized multistage-temperature-control printer. The printed constructs can be perfused via the branched endothelialized vasculatures to support the well-formed 3D capillary networks, which ensure cellular activities with sufficient nutrient supply and then mimic a mature and functional liver tissue in terms of synthesis of liver-specific proteins. Moreover, an inner and external pressure-bearing layer is printed to support the direct surgical anastomosis of the carotid artery to the jugular vein. In summary, a versatile platform to recapitulate the vasculature network is presented, in which case sustaining the optimal cellularization in engineered tissues is achievable.