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Table S2-S3 inlcude siRNAs and primers used in this study.

Associations of selected SNPs in the screening and the replication stages.

Supplementary figure S1-S19 present the results of EWAS analysis and association information of the three novel loci. The data also show the functional and clinical evidence of the three loci associated genes

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10−8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10−9) and one new noncoding variant at 7q21.11 (P < 5 × 10−8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10−8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10−8) and CNFN (P = 3.77 × 10−4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087–97. ©2018 AACR.

Hepatic steatosis plays a detrimental role in the onset and progression of alcohol-associated liver disease (ALD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved protein related to the unfolded protein response. Recent studies have demonstrated that MANF plays an important role in liver diseases. In this study, we investigated the role of MANF in ethanol-induced steatosis and the underlying mechanisms. We showed that the hepatic MANF expression was markedly upregulated in mouse model of ALD by chronic-plus-single-binge ethanol feeding. Moreover, after chronic-plus-binge ethanol feeding, hepatocyte-specific MANF knockout (HKO) mice displayed more severe hepatic steatosis and liver injury than wild-type (WT) control mice. Immunoprecipitation-coupled MS proteomic analysis revealed that arginosuccinate synthase 1 (ASS1), a rate-limiting enzyme in the urea cycle, resided in the same immunoprecipitated complex with MANF. Hepatocyte-specific MANF knockout led to decreased ASS1 activity, whereas overexpression of MANF contributed to enhanced ASS1 activity in vitro. In addition, HKO mice displayed unique urea cycle metabolite patterns in the liver with elevated ammonia accumulation after ethanol feeding. ASS1 is known to activate AMPK by generating an intracellular pool of AMP from the urea cycle. We also found that MANF supplementation significantly ameliorated ethanol-induced steatosis in vivo and in vitro by activating the AMPK signaling pathway, which was partly ASS1 dependent. This study demonstrates a new mechanism in which MANF acts as a key molecule in maintaining hepatic lipid homeostasis by enhancing ASS1 activity and uncovers an interesting link between lipid metabolism and the hepatic urea cycle under excessive alcohol exposure.

Biogas residues (BR) contaminated with potentially toxic metals pose environmental risks to soils and food chains, and strategies are needed to decrease the concentration and bioavailability of potentially toxic metals in BR. Here, metal fractions and removal mechanisms were quantified by synchrotron radiation-based Fourier transform infrared and micro X-ray fluorescence spectromicroscopies on BR and earthworms subject to vermicomposting. Vermicomposting resulted in decreases in concentrations of potentially toxic metals in BR and increases in metal removal efficiencies due to uptake by earthworms. Prior to vermicomposting, Zn, Cu and Pb were associated with N-H, O-H, aromatic C, aliphatic C, and amide functional groups, but following maturation during vermicomposting, metals were associated with N-H, O-H, aliphatic C and polysaccharide functional groups. Following vermicomposting, Zn and Cu were mainly distributed in the dermal portions of earthworms, whereas Pb was more homogeneously distributed among the inner and outer portions of the earthworms, revealing that different metals may have different uptake routes. These findings provide a new strategy for safe utilization of BR by using earthworms via vermicomposting to remove potentially toxic metals and in situ insights into how metals binding and distribution characteristics in BR and earthworms during compost and vermicomposting processes.

Heavy metals in farmland soil are one of the most hazardous pollutants in the environment, owing to their universality and irreversibility. Modified biochar has been widely used in the adsorption and immobilization of heavy metals in soil, and its applicability is mainly determined by the types of heavy metals, pollution levels, and soil environmental conditions. Soil pollution is gradually becoming more complex and diversified, and heavy metal pollutants mostly occur in the form of compound pollution. However, most studies have focused on single heavy metal pollutant or the addition of heavy metal to soil. This study used rice straw as a raw material to prepare biochar, and modified it with K

Acute lung injury (ALI) is an urgent respiratory disease without effective treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF)has been demonstrated to play a suppressive role in some inflammatory conditions. However, the effect of MANF on ALI has not yet been reported. In this study, we collected bronchoalveolar lavage fluid (BALF) from the patients with or without pulmonary inflammation, and used lipopolysaccharide (LPS) to induce mice ALI model. Mono-macrophage-specific MANF knockout (MKO) mice were constructed and recombinant human MANF protein was used to ALI mice. We found that the endogenous MANF protein in both human BALF and mice lung tissues was increased in inflammatory conditions. MANF level in the macrophages of inflammatory lung was higher than that in normal controls in both human and mice. MANF deficiency in macrophages induced lung inflammation and aggravated LPS-induced lung injury. MANF lowered LPS-induced lung injury, inhibited macrophage polarization to M1 functional type. Meanwhile, MANF inhibited-LPS induced activation of NF-κB signal pathway by down regulating phosphorylated p65in lung tissue and macrophages. These results indicate that MANF acts as a suppressor in ALI via negatively regulating NF-κB activation and macrophages polarization, which may be a novel potential target and shed light on ALI therapy.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10−8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10−9) and one new noncoding variant at 7q21.11 (P < 5 × 10−8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10−8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10−8) and CNFN (P = 3.77 × 10−4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development. Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087–97. ©2018 AACR.

A new and recyclable protocol was developed for Pd(OAc) 2 -catalyzed the cross-coupling reaction of terminal alkynes with arylboronic acids using environmentally friendly H 2 O/TBAB as reaction medium. A series of cross-coupling products containing internal acetylenic bond can be obtained with good selectivity and yield. The Pd(OAc) 2 /H 2 O/TBAB system was stable in the Sonogashira-type cross-coupling reaction and could be used at least three cycles without considerable decrease in catalytic performance. The results suggest that the unsupported and recyclable systems can be extended to the other realm of C C bond formation in synthetic organic chemistry.

It has been confirmed that exercise preconditioning (EP) has a protective effect on acute cardiovascular stress. However, how Hsp70 participates in EP-induced cardioprotection is unknown. EP may involve Hsp70 to repair unfolded proteins or may also stabilize the function of the endoplasmic reticulum via Hsp70-related autophagy to work on a protective formation. Our EP protocol involves four periods of 10 min running with 10 min recovery intervals. We added a period of exhaustive running to test this protective effect, using histology and molecular biotechnology methods to detect related markers. EP provided cardioprotection at its early and late phases against exhaustive exercise-induced ischemic myocardial injury. Results showed that Hsp70 co-chaperone protein BAG3, ubiquitin adaptor p62 and critical autophagy protein LC3 were significantly upregulated at the early phase. Meanwhile, Hsp70, Hsp70/BAG3 co-localization extent, LC31 and LC3II were significantly upregulated at the late phase. Hsp70 mRNA levels and LC3II/I ratios were also consistent with the extent of myocardial injury following exhaustive exercise. Hsp70 increase was delayed relative to BAG3 and p62 after EP, indicating a pre-synthesized phenomenon of BAG3 and p62 for chaperone-assisted selective autophagy (CASA). The decreased Hsp70, BAG3 and p62 levels and increased Hsp70/BAG3 co-localization extent and LC3 levels induced by exhaustive exercise after EP suggest that EP-induced cardioprotection might associate with CASA. Hsp70 has a cardioprotective role and has a closer link with CASA in LEP. Additionally, EP may not cause exhaustion-dependent excessive autophagy regulation. Collectively, during early and late EP, CASA potentially plays different roles in cardioprotection.

Mesencephalic astrocyte‑derived neurotrophic factor (MANF) is an endoplasmic reticulum stress‑inducible protein, which has been suggested to be upregulated in inflammatory diseases; however, how inflammation regulates its transcription remains unclear. Activator protein‑1 (AP‑1), which is a transcription factor complex composed of c‑Fos and c‑Jun, is activated during the inflammatory process. The present study aimed to investigate whether the AP‑1 complex regulates MANF transcription. The results of a luciferase reporter assay revealed that one of three putative AP‑1 binding sites in the MANF promoter region is essential for enhancement of MANF transcription. Mechanistically, AP‑1 was revealed to directly bind to the promoter region of the MANF gene by chromatin immunoprecipitation assay. Furthermore, MANF was strongly expressed in the liver tissues of patients with hepatitis B virus (HBV) infection, compared with in normal liver tissues from patients with hepatic hemangioma. Furthermore, c‑Fos and c‑Jun were also upregulated in the nuclei of hepatocytes from patients with HBV infection. In mice treated with carbon tetrachloride, the expression patterns of MANF, c‑Fos and c‑Jun were similar to those in patients with HBV. These results suggested that the AP‑1 complex may be a novel regulator of MANF transcription, which may be involved in liver inflammation and fibrosis.

In order to study the impact of turning on physicochemical properties, oxygen supply and odor emission during composting, the physicochemical properties, oxygen, odor and volatile organic compounds concentrations before and after turning were investigated. Results showed that turning can accelerate the temperature, density and moisture decrease. Among the four times turning, the first turning influnenced pile temperature, porosity and odor emission deepest which the temperature and density decreased 16.9% and 22.2% respectively after turning than before, while the NH3 and VOCs emission were higher than 115% and 150% respectively than before. However, the forth turning effected moisture change deepest which decreased 6% than before. The other turings didn’t effect pile parameters significantly. Considering energy saving and parameter changes, it’s suggested to reduce the turning frequency. Moeover, proper measures should be adopted to controll odor spread during first turning.

Aims To study the protective effects of late remote ischaemic preconditioning (RIPC) against myocardial ischaemia/reperfusion (I/R) injury and determine whether Stat5 is involved in this protection by using cardiomyocyte-specific Stat5 knockout mice (Stat5-cKO). Methods and results Mice were exposed to lower limb RIPC or sham ischaemia. After 24 h, the left anterior descending artery (LAD) was ligated for 30 min, then reperfused for 180 min. The myocardial infarct size (IS), apoptotic rate of cardiomyocytes, and serum myocardial enzymes were measured to evaluate for cardioprotective effects. Heart tissues were harvested to determine the cardiomyocytes' anti-apoptotic and survival signaling. When compared with the Stat5fl/fl mice without RIPC, Stat5fl/fl mice with RIPC (Stat5fl/fl+RIPC + I/R) displayed a decreased myocardial IS/LV (16 ± 1.5 vs. 30.1 ± 3.1%, P < 0.01; IS/ area at risk (AAR), 42.2 ± 3.5 vs. 69.2 ± 4.9%, P < 0.01), a reduced cardiomyocyte apoptotic rate (2.1 ± 0.37 vs. 5.5 ± 0.53%, P < 0.01), and lower creatine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) levels. To the contrary, the Stat5-cKO mice (Stat5fl/fl; Tnnt2Cremice with Doxycycline treatment for 7 days) did not exhibit any effect of RIPC-induced cardioprotection. Activation of STAT5 protein was significantly higher in the Stat5fl/fl+RIPC + I/R group than in the Stat5fl/fl+I/R group, while there was no significant difference between the Stat5-cKO + RIPC + I/R and the Stat5-cKO + I/R group. Further analyses with heart tissues detected decreased protein expressions of cytochrome c (Cyt c) and cleaved Caspase-3 in the Stat5fl/fl+RIPC + I/R mice, along with increased anti-apoptotic molecules, including B-cell lymphoma-extra large (Bcl-xL) and B-cell lymphoma-2 (Bcl-2); such changes were not noted in the Stat5-cKO + RIPC + I/R mice. Additionally, RIPC increased cardiac hypoxia inducible factor-1 (HIF-1α) and interleukin-10 (IL10) protein levels and caused activation of AKT, phosphatidylinositol 3 kinase (PI3K), and vascular endothelial growth factor in the heart of the Stat5fl/fl mice. However, these changes were completely inhibited by the absence of Stat5. Conclusions These results suggest that RIPC-induced late cardioprotection against myocardial I/R injury is Stat5-dependent and is correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling.

The objective of this study was to investigate the late cardiac effect of exercise preconditioning (EP) on the exhaustive exercise-induced myocardial injury in rats and the role of protein kinase C (PKC) in EP. Rats were subjected to a run on the treadmill for four periods of 10 min each at 30 m/min with intervening periods of rest of 10 min as an EP protocol. The exhaustive exercise was performed 24 h after EP. PKC inhibitor chelerythrine (CHE) was injected before EP. The results showed that EP increased the running ability of rats, and alleviated the exhaustive exercise-induced injury in cardiomyocytes, but pretreatment with PKC inhibitor CHE did not abolish the late phase cardioprotection of EP. A significant increase of PKCδ, both at the protein level and the mRNA level in the left ventricular myocardium of rats, accompanied by its activated form (phosphorylated on Thr507, p-PKCδThr507) translocated to intercalated disks and was found in the late phase of EP. This circumstance was not attenuated by CHE. These results suggested that a high level of PKCδ might be involved in cardioprotection against myocardial damage, but if activated PKCδ at reperfusion took on a key role in cardioprotection was still an outstanding question.

BACKGROUND Exercise preconditioning (EP) can provide powerful protection to the heart. Evidence supports the contention that EP directly enhances myocardial tolerance to ischaemia through a protein kinase C (PKC)-mediated mechanism. However, studies investigating the role of isoform-specific PKC after EP are lacking. METHODS AND RESULTS In this study, a male Sprague-Dawley rat model of EP was established (4 periods of 30 m/min for 10 min exercise then a 10 min rest at 0% grade treadmill exercise). Rats were subjected to exhaustive exercise to induce myocardial injury. Chelerythrine (5 mg/kg) was injected before EP to investigate the role of PKC in EP. EP was found to attenuate exhaustive exercise-induced myocardial injury in both of EP's 2 protective phases, especially the latter phase. After EP, PKCe was markedly upregulated, and PKCe was translocated to myocardial intercalated disks, and p-PKCe(Ser729) was translocated to the myocardial cytomembrane. Even though PKCe was markedly upregulated and translocated to intercalated disks during exhaustive exercise, p-PKCe(Ser729) was mainly distributed in the cytoplasm. A chelerythrine injection before EP did not suppress the activation of PKC and the protection of EP. CONCLUSIONS These results indicate that PKCe plays an important role in EP-mediated protection of the myocardium during exhaustive exercise-induced myocardial injury, and that a chelerythrine injection during exercise is not suitable for demonstrating the role of PKCe.

A novel tetranuclear lead-edta compound [Pb4(edta)(H2O)2(N3)4]n (1) (H4edta = ethylenediaminetetraacetic acid) has been synthesized by the reaction of PbF2 with H4edta and NaN3 mixed-ligands under hydrothermal conditions, and was characterized by elemental analysis, thermal analysis, luminescence, powder X-ray diffraction and single-crystal X-ray diffraction. The results of X-ray crystallographic analysis reveal that compound 1 is the first 3D Pb(II)-edta coordination polymer with a high ratio of lead. Remarkably, the edta4− ligand uses all its 10 donor atoms (8O ​+ ​2 ​N) coordinated to Pb(II) ions and formed a 2D layer. The 2D layers are further linked to a complex 3D coordination polymer by the inorganic chain [Pb5(N3)10]n. Time-dependent density functional theory (TDDFT) calculations reveal that the mechanism of the fluorescence emission is dominantly resulted from the ligand-to-metal charge transfer (LMCT) for 1, which is in good agreement with its fluorescence spectra and crystal structure. Optical absorption spectra indicate that 1 has wide optical band-gaps and can be probably used as wide optical band-gap semiconductor material.

The objective of this study was to investigate the late cardioprotective effect of exercise preconditioning (EP) on isoproterenol (ISO)-induced myocardial injury in rats and the role of protein kinase C (PKC) in EP. Rats were injected with ISO 24 h after running on a treadmill for four periods of 10 min each at 28-30 m/min with intervening periods of rest of 10 min. Nonselective PKC inhibitor chelerythrine (CHE) was injected before EP. The myocardial injury was evaluated quantitatively in terms of the serum cardiac troponin I (cTnI) levels, the myocardial ischemia/hypoxia area, and the integral optical density (IOD) of haematoxylin-basic fuchsin-picric acid (HBFP) staining, and qualitatively in terms of the myocardial ultrastructure. EP markedly attenuated the ISO-induced myocardial ischemia/hypoxia and ultrastructural damage with lower serum cTnI levels. CHE injection before EP did not block the protective effect of EP, displaying a mild myocardial ischemia/hypoxia and well-preserved ultrastructure with even lower serum cTnI levels. The results indicate that EP can exert a late cardioprotection against ISO-induced myocardial injury, and that an injection of the nonselective PKC inhibitor CHE before EP may have a different effect on ISO-induced myocardial injury. Further investigation needs to be conducted to define the role of different PKC isozymes in EP by using isozyme-selective inhibitors.

An oligonucleotide biochip that specifically detects point mutations in the gyrA and parC genes of Neisseria gonorrhoeae was designed and subsequently evaluated with 87 untreated clinical specimens. The susceptibilities of the N. gonorrhoeae strains were tested to determine the prevalence of ciprofloxacin-resistant strains in Anhui Province, People's Republic of China. Conventional DNA sequencing was also performed to identify mutations in gyrA and parC and to confirm the biochip data. The study demonstrates that all of the point mutations in the gyrA and parC genes of N. gonorrhoeae were easily discriminated by use of the oligonucleotide biochip. Fifteen different alteration patterns involved in the formation of ciprofloxacin resistance were identified by the biochip assay. Double mutations in both Ser91 and Asp95 of the GyrA protein were seen in all nonsensitive isolates. Double mutations in Ser91 and Asp95 of GyrA plus mutation of Glu91 or Ser87 of the ParC protein lead to significant high-level resistance to ciprofloxacin in N. gonorrhoeae isolates. The results obtained by use of the oligonucleotide biochip were identical to those obtained by use of DNA sequencing. In conclusion, the oligonucleotide biochip technology has potential utility for the rapid and reliable identification of point mutations in the drug resistance genes of N. gonorrhoeae.

The objective of this study was to investigate the early cardioprotective effect of exercise preconditioning (EP) on the exhaustive exercise-induced myocardial injury in rats and the role of protein kinase C delta isoform (PKCδ) in EP. Rats were subjected to run on the treadmill for four periods of 10 min each at 30 m/min with intervening periods of rest of 10 min as an EP protocol. The exhaustive exercise was performed 0.5 h after EP. PKC inhibitor chelerythrine (CHE) was injected before EP. Our results showed that EP markedly attenuated the exhaustive exercise-induced myocardial ischemia/hypoxia, ultrastructural damage, high serum cTnI, and NT-proBNP levels. CHE injection before EP did not abolish the protection of EP. Both exhaustive exercise and EP produced a significant increase in PKCδ and p-PKCδ(Thr507) protein levels in cardiomyocytes. However, the immunostaining of p-PKCδ(Thr507) in EP cardiomyocytes was primarily localized to intercalated disks and nuclei while the exhaustive exercise-induced high level p-PKCδ(Thr507) was mainly distributed in the cytoplasm. Moreover, the high PKCδ and p-PKCδ(Thr507) levels in exhaustive exercise were significantly down-regulated by EP. CHE did not attenuate the expressions of PKCδ and p-PKCδ(Thr507). These results indicate that an appropriate activation and translocation of PKCδ may represent a mechanism whereby EP can exert an early cardioprotection against exhaustive exercise-induced myocardial injury.

Aimed at controlling the nitrogen loss caused by the ammonia gas emission during composting, the mixtures of magnesium hydroxide [Mg(OH)2] and phosphoric acid (H3PO4) were added into composting materials of swine manure and cornstalk. After 26 d composting, ammonical nitrogen and total nitrogen were improved obviously,which were 10.7 g x kg(-1) and 36.9 g x kg(-1) respectively in amended treatment (B), while they were 7.7 g x kg(-1) and 26.8 g x kg(-1) in un-amended trial. By analysis of the total organic carbon, t suggested that amendments accelerated the degradation of organic matter, germination index test showed the maturity of trial B(96%) was better than trial A(82%) in final compost. The scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis confirmed the existence of struvite (MgNH4PO4 x 6H2O). These results indicated that Mg (OH)2 and H3PO4 could accelerate the degradation of organic matter, and reduce the ammonia emission by struvite crystallization reaction.

PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of PSORS1 where multiple biologically plausible candidate genes were suggested. The most recent study has indicated HLA-Cw6 as the primary PSORS1 risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the PSORS1 locus was performed by analyzing 10 polymorphic microsatellite markers from the PSORS1 region as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P, Author Summary Psoriasis is a common skin disease with strong genetic risk. The analysis of psoriatic families with multiple affected individuals has identified several genomic regions that are linked (showing linkage evidence) to the development of psoriasis. Of them, the region on 6p21.3 (PSORS1) is a well-confirmed major risk locus. The identification of the disease risk gene within the PSOR1 locus, however, has been difficult, largely due to the fact that several genes show evidence for association with the disease development and the evidences are highly correlated and hard to be separated from each other. In this study, we performed a fine mapping study of the PSORS1 locus in Chinese families with psoriasis. By analyzing recombinant haplotypes that carry different risk-associated genetic variants within different genes, we were able to separate the genetic effects observed within multiple genes and identify strong supporting evidence for HLA-C to be the primary risk gene of the PSORS1 locus. We have further demonstrated that the genetic variation within the HLA-C gene does not explain the full linkage evidence at the PSORS1 locus, suggesting that there might be other risk genes and/or alleles within the region. Our findings have improved our understanding about the genetic complexity of the PSORS1 locus.

A series of M(CO)L, M(CO)4L2 and [M(CO)5]2L′ (M = Cr, Mo, W; L = 2-diphenylphosphinopyridine (Ph2Ppy); L′ = 3,6-bis(diphenylphosphino)pyridazine (dppz)) complexes were prepared by oxygen atom transfer reaction and their spectra features are discussed. The molecular structure of Cr(CO)5dppzO (dppzO = 3-diphenylphosphino-6-diphenylphospholylpyridazine) has been determined by X-ray crystallography. The complex crystallize in the triclinic space group P1 with two molecules per unit cell of dimensions a 10.522(3), b 12.487(5), c 12.711A, α 109.03(3)°, β 100.39(2)° and 94.53(3)°. Full-matrix least-squares refinement yielded R 0.060 for 2009 reflections.

To study a Chinese pedigree with Hailey-Hailey disease (HHD) and examine the ATP2C1 gene mutation in this family.All exons of ATP2C1 gene were analyzed with polymerase chain reaction and DNA sequencing in all patients of this family and 100 unrelated population-match controls.We identified a novel heterozygous nucleotide A --G transition at position 235 - 2 in intron 3 of ATP2C1 gene. This splice site mutation was not found in the healthy members of this pedigree and in the controls.The splicing mutation can affect the result of transcription and translation, and it is a specific novel mutation of ATP2C1 gene.

To identify the mutations of ED1 gene in a family with X-linked hypohidrotic ectodermal dysplasiaEight coding exons of ED1 gene of two patients with clinically confirmed X-linked hypohidrotic ectodermal dysplasia, their parents, and 100 unrelated population-matched control were amplified by polymerase chain reaction. The products were further analyzed by direct sequencing.Two patients with X-linked hypohidrotic ectodermal dysplasia in this pedigree showed a point mutation at nucleotide 1 045 ( AG) . Meanwhile, heterozygous double peaks of nucleotide G and A at the same position were found in their mother, but not in their father and 100 unrelated population-matched controls.The c. 1 045AG mutation of ED1 gene may be the pathologic cause of this Chinese family with X-linked hypohidrotic ectodermal dysplasia.

Dyschromatosis symmetrica hereditaria (OMIM127400) is a rare autosomal dominant pigmentary genodermatosis caused by mutations in the RNA-specific adenosine deaminase (ADAR) gene. This study investigated 5 families and 3 sporadic patients with dyschromatosis symmetrica hereditaria in the Chinese Han population from Anhui province, China. By direct sequencing, 5 novel ADAR gene mutations (c.982C>T, c.1491insA, c.2568_2571delTAAC, c.2969C>G and c.3040G>T) and 3 mutations described previously (c.3203-2A>G, c.3247C>T and c.3286C>T) were identified, all of which were heterozygous. We reviewed a total of 48 mutations in the ADAR gene in patients with dyschromatosis symmetrica hereditaria by previous reports and speculated that the mutation hotspots on the ADAR gene might be located in exons 9-15. The tRNA-specific and double-stranded RNA adenosine deaminase domain is essential for the deaminase activity of the ADAR encoded protein.

Darier's disease (DD) is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. To date, at least 140 mutations in the ATP2A2 gene have been identified as the genetic basis of DD. Here we reported three familial and two sporadic Chinese DD patients totally with four missense mutations (N767D, M494I, M494L, C318F) and one splice-site mutation (1288-6A--G) in ATP2A2 gene, and presented a literature review of DD cases reported in China since 1989. Our data add new variants to the repertoire of ATP2A2 gene in DD and confirms that most mutations in the ATP2A2 gene are private and missense type. Likewise, the literature review indicates that DD is not uncommon in China and presents more information about genotype-phenotype correlations.