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OBJECTIVE Conversion of normal cells to cancer cells is often accompanied by abnormal synthesis of serum enzymes. Both alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been reported to have prognostic value in a variety of malignancies. The aim of this study was to investigate the effect of preoperative serum ALP and LDH levels on the prognosis of patients with periampullary carcinoma who underwent pancreatoduodenectomy (PD). METHODS According to the preoperative ALP or LDH values, 856 cancer patients receiving PD treatment from January 2001 to January 2019 were divided into high-ALP group and low-ALP group or high-LDH group and low-LDH group. Statistical analysis was carried out to study the differences between the high-ALP and low-ALP groups or the high-LDH and low-LDH groups. Furthermore, the possibility of preoperative ALP or LDH as prognostic factor of periampullary carcinoma was investigated. RESULTS In both the high-ALP and the high-LDH groups, the prognosis of patients with periampullary carcinoma who underwent PD was worse than that of the low-ALP and low- LDH group. Even through risk factor analysis, it was found that preoperative ALP and LDH could be independent prognostic factor for patients with periampullary carcinoma who underwent PD. CONCLUSION Preoperative ALP or LDH is an independent risk factor for periampullary carcinoma.

Drought is a major concern among abiotic stresses in wheat (Triticum aestivum L.) production. Breeding resistant cultivars are the most effective means to manage drought stress. F6 recombinant inbred lines (RIL) derived from the cross of Berkut/Worrakatta were used to identify quantitative trait loci (QTL) for drought tolerance at germination stage under treatment of PEG6000 using the wheat 50 K single nucleotide polymorphism (SNP) array. Twenty-eight linkage groups were constructed, covering a length of 2220.26 cM. Eighteen QTL were detected based on the drought tolerance coefficients and D-value, explaining 2.7–6.5% of the phenotypic variances, in which 15 were likely to be novel. Three QTL, QGR.xjau-5AS, QCL.xjau-5AS and QD.xjau-5AS for GR, CL and D-value, respectively, at physical positions of 11.70–20.61 Mb between markers AX-111258240 and AX-94458300 on chromosome 5AS accounted for 3.4–4.8% of the phenotypic variances. Three QTL, QGP.xjau-5DL, QSH.xjau-5DL and QD.xjau-5DL for GP, SH and D-value, respectively, were flanked by markers AX-94524442 and AX-110998507 at 560.42–567.39 Mb on chromosome 5DL, accounting for 4.4–6.5% of the phenotypic variances. In addition, the candidate genes TraesCS5A02G022100, TraesCS5B02G014200 and TraesCS5D02G563900 were predicted. Based on transcriptional expression data, the results showed that the expression level of TaGATAs-5A, TaUbox-5B and TaGSTP-5D changed with the increase of treatment time under drought stress in tolerant and sensitive varieties. These are interesting targets in mining drought tolerance genes and the improvement of drought tolerance in wheat.

Background Chromosome 1p36 deletion syndrome is a contiguous genetic disorder with multiple congenital anomalies and mental retardation. It has been emerging as one of the most common terminal deletion syndromes in humans with the rapid utility of microarray analysis. However, the prenatal findings of 1p36 deletion syndrome are still limited. We report a fetus with 1p36 deletion and cardiac phenotype of dextrocardia, combined with a balanced translocation between chromosome 5 and 6. The phenotype of dextrocardia is rarely reported in prenatal 1p36 deletion cases. Case presentation We present a prenatal 1p36 deletion case with congenital heart diseases and single umbilical artery. Fetal echocardiography showed dextrocardia, ventricular septal defect and pericardial effusion. Fetal karyotype revealed a de novo balanced translocation of 46,XY,t(5;6)(q11.2;q23.3). Chromosomal microarray analysis detected a pathogenic deletion in 1p36.21p36.12, with the size of 6.38 Mb. Further whole genome sequencing revealed that the balanced translocation disrupted the EYA4 and ITGA1 genes. Conclusions Although congenital heart diseases are very common clinical manifestations among patients with 1p36 deletion, dextrocardia is a quite rare cardiac phenotype. This is the second case with 1p36 deletion and dextrocardia, and the first prenatally diagnosed 1p36 deletion case with dextrocardia. Our case indicates that genes in 1p36 are associated with not only heart structural anomalies, but also cardiac laterality development. Our results also imply that the EYA4 gene disrupted by the balanced translocation might be related with the cardiac development.

NAC (NAM, ATAF1/2, and CUC2) transcription factors play important roles in fruit ripening and quality. The watermelon genome encodes 80 NAC genes, and 21 of these NAC genes are highly expressed in both the flesh and vascular tissues. Among these genes, ClNAC68 expression was significantly higher in flesh than in rind. However, the intrinsic regulatory mechanism of ClNAC68 in fruit ripening and quality is still unknown. In this study, we found that ClNAC68 is a transcriptional repressor and that the repression domain is located in the C-terminus. Knockout of ClNAC68 by the CRISPR-Cas9 system decreased the soluble solid content and sucrose accumulation in mutant flesh. Development was delayed, germination was inhibited, and the IAA content was significantly decreased in mutant seeds. Transcriptome analysis showed that the invertase gene ClINV was the only gene involved in sucrose metabolism that was upregulated in mutant flesh, and expression of the indole-3-acetic acid-amido synthetase gene ClGH3.6 in the IAA signaling pathway was also induced in mutant seeds. EMSA and dual-luciferase assays showed that ClNAC68 directly bound to the promoters of ClINV and ClGH3.6 to repress their expression. These results indicated that ClNAC68 positively regulated sugar and IAA accumulation by repressing ClINV and ClGH3.6. Our findings provide new insights into the regulatory mechanisms by which NAC transcription factors affect fruit quality and seed development.

NAC (NAM, ATAF1/2, and CUC2) transcription factors play important roles in fruit ripening and quality. The watermelon genome encodes 80 NAC genes, and 21 of these NAC genes are highly expressed in both the flesh and vascular tissues. Among these genes, ClNAC68 expression was significantly higher in flesh than in rind. However, the intrinsic regulatory mechanism of ClNAC68 in fruit ripening and quality is still unknown. In this study, we found that ClNAC68 is a transcriptional repressor and that the repression domain is located in the C-terminus. Knockout of ClNAC68 by the CRISPR-Cas9 system decreased the soluble solid content and sucrose accumulation in mutant flesh. Development was delayed, germination was inhibited, and the IAA content was significantly decreased in mutant seeds. Transcriptome analysis showed that the invertase gene ClINV was the only gene involved in sucrose metabolism that was upregulated in mutant flesh, and expression of the indole-3-acetic acid-amido synthetase gene ClGH3.6 in the IAA signaling pathway was also induced in mutant seeds. EMSA and dual-luciferase assays showed that ClNAC68 directly bound to the promoters of ClINV and ClGH3.6 to repress their expression. These results indicated that ClNAC68 positively regulated sugar and IAA accumulation by repressing ClINV and ClGH3.6. Our findings provide new insights into the regulatory mechanisms by which NAC transcription factors affect fruit quality and seed development.

Abscisic acid (ABA) is a critical regulator of seed development and germination. β-glucosidases (BGs) have been suggested to be contributors to increased ABA content because they catalyze the hydrolysis of ABA-glucose ester to release free ABA. However, whether BGs are involved in seed development is unclear. In this study, a candidate gene, ClBG1, in watermelon was selected for targeted mutagenesis via the CRISPR/Cas9 system. Seed size and weight were significantly reduced in the Clbg1-mutant watermelon lines, which was mainly attributed to decreased cell number resulting from decreased ABA levels. A transcriptome analysis showed that the expression of 1015 and 1429 unique genes was changed 10 and 18 days after pollination (DAP), respectively. Cytoskeleton- and cell cycle-related genes were enriched in the differentially expressed genes of wild type and Clbg1-mutant lines during seed development. Moreover, the expression of genes in the major signaling pathways of seed size control was also changed. In addition, seed germination was promoted in the Clbg1-mutant lines due to decreased ABA content. These results indicate that ClBG1 may be critical for watermelon seed size regulation and germination mainly through the modulation of ABA content and thereby the transcriptional regulation of cytoskeleton-, cell cycle- and signaling-related genes. Our results lay a foundation for dissecting the molecular mechanisms of controlling watermelon seed size, a key agricultural trait of significant economic importance.

Aim: The purpose of this study was to evaluate the clinical utility of pharmacogenetic (PGx) testing in the treatment of bipolar disorder in the Chinese population. Patients & methods: Compare efficacy and side effects, measured by the Clinical Global Impression Efficacy Index scale (CGI-EI), of PGx-guided treatment (n = 100) to that of the traditional treatment (n = 100). Results: Compared with the traditional treatment, PGx-guided treatment reduced the number of medications used for patients, also achieving better efficacy at 4, 8 and 12 weeks. In the analysis of side effects, the PGx-guided group significantly reduced the side effects. Conclusion: Our study suggests that PGx testing results-guided treatment is superior to the traditional treatment of bipolar disorder in the Chinese population.

Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted therapy. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. To investigate the functional role of protocadherin alpha 3 (PCDHA3) in LUSC, as well as investigate the underlying molecular mechanism. Data for PCDHA3 expression and clinical information in The Cancer Genome Atlas (TCGA) were extracted and analyzed in the UALCAN platform. Expression levels of PCDHA3 in LUSC cell lines were analyzed via RT-PCR and western blot. Overexpression of PCDHA3 was conducted via plasmid transfection. CCK-8 and cell cycle assays were utilized to investigate effect of PCDHA3 on cell proliferation. Transwell assay was used to detect migration and invasion. The underlying mechanism was demonstrated via western blot analysis. Our data indicate that PCDHA3 was low expressed in three kinds of LUSC cell lines and best in H520 cells. Furthermore, overexpression of PCDHA3 could significantly impair LUSC cells proliferation, invasion and migration. Moreover, PCHDA3 repressed the biomarkers of mesenchymal (N-cadherin, fibronectin and vimentin) and increased expression of epithelial markers (E-cadherin and α-catenin). On the other hand, PCDHA3 overexpression partially blocked epithelial-mesenchymal transition. PCDHA3 suppressed the LUSC cells proliferation, invasion and migration via inhibiting the expression of EMT signatures, suggesting that PCDHA3 could serve as a valuable therapeutic target for LUSC therapy.

International audience; Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

The inhibition of metastatic progression of Somatostatin receptor type 2 (SSTR2) gene transfection mediated by adenovirus in human pancreatic carcinoma cells and the mechanism involved in this effect were studied. The full-length human SSTR2 cDNA was introduced into the pancreatic cancer cell line BXPC-3 by adenovirus-mediated transfection. Stable expression of mRNAs and protein of SSTR2 was detected by RT-PCR and Western-blot. The Matrigel-coated Transwell was used to detect the migratory and invasive ability of SSTR2-expressing cells, Adv-GFP control cells and mock control cells. Furthermore, the expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was detected by RT-PCR in these cells. The stable expression of SSTR2 was detected in BXPC-3 transfected by Adv-GFP-SSTR2. A dramatic decrease of BXPC-3 expressing sst2 cells migrating through a Matrigel-coated filter was observed, as compared with Adv-GFP control and mock control cells (P