Light quality surrounding a plant is largely determined by the density of its neighboring vegetation. Plants are able to sense shade light signals and initiate a series of adaptation responses, which is known as shade avoidance syndrome (SAS). PHYTOCHROME INTERACTING FACTORS (PIFs) are key factors in SAS network by regulating the biosynthesis of multiple phytohormones and the expression of cell expansion genes. The transcriptional regulation of PIFs in response to shade remains poorly understood. Here we show that TCP17 and its two closely related homologs, TCP5 and TCP13 play an important role in mediating shade-induced hypocotyl elongation by up-regulating auxin biosynthesis via a PIFs-dependent and a PIFs-independent pathway. In constitutive white light (Wc), a tcp5,13,17 triple mutant (3tcp) showed a subtle hypocotyl defective phenotype. In shade, however, it showed a significantly reduced hypocotyl elongation phenotype, indicating a positive role of TCPs in regulating SAS. Our in depth biochemical and genetic analyses indicated that TCP17 can significantly accumulate in shade. TCP17 binds to the promoters of PIFs and YUCCAs (YUCs) to indirectly or directly up-regulate auxin levels in shade. These data provide new insights into our better understanding of the regulatory mechanisms of SAS in plants.

Non-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population, OBJECTIVE: The aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients. In this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case-control and family-based associations were analyzed. The case-control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p=0.04) and non-syndromic cleft lip and palate (p=0.01), but not associated with non-syndromic cleft lip only and non-syndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG+AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p=0.04, OR=2.05, 95% CI: 1.01-4.16) and non-syndromic cleft lip and palate (p=0.01, OR=3.94, 95% CI: 1.34-11.54). In addition, we did not detect any transmission-disequilibrium in rs7078160 (p=0.68). This study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.

Background: Although head and neck squamous cell carcinoma (HNSCC) is a common malignancy, the molecular biology landscape underlying its occurrence and development remains poorly understood. The family with sequence similarity (FAM) 3 family of proteins includes four family members, namely FAM3A, FAM3B, FAM3C and FAM3D. In particular, FAM3C has been previously reported to be closely associated with various human malignancies. Methods: Combining analyses using The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource and MethSurv databases, coupled with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes bioinformatics tools, the possible biological function and key pathways regulated by the FAM3 family in HNSCC were probed. Results: High FAM3A expression was found to increase HNSCC mitochondrial biosynthesis and energy metabolism, inhibit immune cell infiltration in the HNSCC tumor microenvironment, and be associated with poor prognosis. By contrast, lower expression levels of FAM3B in HNSCC were associated with a poorer prognosis in patients with HNSCC. This was most likely due to the finding that FAM3B can inhibit the development of HNSCC by increasing immune cell infiltration, inhibiting epithelial-mesenchymal transition (EMT) and the cytochrome P450 pathway. FAM3C was overexpressed in oral squamous cell carcinoma (OSCC) and associated with increased OSCC cell stemness, immune escape and EMT. In the present study, FAM3C expression was associated with poor prognosis for patients with HNSCC by suppressing tumor immune cell infiltration. FAM3C expression was also positively correlated with the expression of epithelial and mesenchymal markers such as E-cadherin, N-cadherin, Vimentin and ZO-1, which may promote the partial EMT status in HNSCC and greatly increase its malignancy. FAM3D is a maintenance factor of the epithelial phenotype in HNSCC that can inhibit the progression of EMT, promote tumor immune cell infiltration and inhibit HNSCC progression. In addition, methylation levels of the FAM3 gene family were correlated with the overall survival rate of HNSCC. Conclusion: The FAM3 family may be applied as a biomarker and potential therapeutic target for HNSCC.

Background: S100 calcium-binding protein A6 (S100A6) is a calcium-binding protein that is involved in a variety of cellular processes, such as proliferation, apoptosis, and the cellular response to various stress stimuli. However, its role in NAFLD and associated metabolic diseases remains uncertain. Methods and Results: In this study, we revealed a new function and mechanism of S100A6 in NAFLD. S100A6 expression was upregulated in human and mouse livers with hepatic steatosis, and the depletion of hepatic S100A6 remarkably inhibited lipid accumulation, insulin resistance, inflammation, and obesity in a high-fat, high-cholesterol (HFHC) diet-induced murine hepatic steatosis model. In vitro mechanistic investigations showed that the depletion of S100A6 in hepatocytes restored lipophagy, suggesting S100A6 inhibition could alleviate HFHC-induced NAFLD. Moreover, S100A6 liver-specific ablation mediated by AAV9 alleviated NAFLD in obese mice. Conclusions: Our study demonstrates that S100A6 functions as a positive regulator of NAFLD, targeting the S100A6-lipophagy axis may be a promising treatment option for NAFLD and associated metabolic diseases. Export