A 66-Nuclear All-Alkynyl Protected Peanut-Shaped Silver(I)/Copper(I) Heterometallic Nanocluster: Intermediate in Copper-Catalyzed Alkyne-Azide Cycloaddition.

Ligand-protected heterometallic nanoclusters in contrast to homo-metal counterparts show more broad applications due to the synergistic effect of hetero-metals but their controllable syntheses remain a challenge. Among heterometallic nanoclusters, monovalent Ag-Cu compounds are rarely explored due to much difference of Ag(I) and Cu(I) such as atom radius, coordination habits, and redox potential. Encouraged by copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, comproportionation reaction of Cu(II)X2 and Cu(0) in the presence of (PhC≡CAg)n complex and molybdate generated a core-shell peanut-shaped 66-nuclear Ag(I)-Cu(I) heterometallic nanocluster, [(Mo4O16)2@Cu12Ag54(PhC≡C)50] (referred to as Ag54Cu12). The structure and composition of Ag-Cu heterometallic nanocluster are fully characterized. X-ray single crystal diffraction reveals that Ag54Cu12 has a peanut-shaped silver(I)/copper(I) heterometallic nanocage protected by fifty phenylacetylene ligands in µ3-modes and encapsulated two mutually twisted tetramolybdates. Heterometallic nanocage contains a 54-Ag-atom outer ellipsoid silver cage decorated by 12 copper inside wall. Nanosized Ag54Cu12 is a n-type narrow-band-gap semiconductor with a good photocurrent response. Preliminary experiments demonstrates that Ag54Cu12 itself and activated carbon supported Ag54Cu12/C are effective catalysts for 1,3-dipole cycloaddition between alkynes and azides at ambient conditions. The work provides not only a new synthetic route toward Ag(I)-Cu(I) nanoclusters but also an important heterometallic intermediate in CuAAC catalytic reaction.

Plant-based dietary patterns and lung cancer mortality: a perspective cohort study.

Plant-based diets are recommended for cancer survivors; however, their effects on lung cancer mortality are limited. We conducted this study to evaluate the association between plant-based dietary patterns and lung cancer mortality. A total of 408 newly diagnosed lung cancer patients aged 18 to 79 years were enrolled in the study. Dietary intake was assessed using a validated 111-item food frequency questionnaire (FFQ). The survival status was confirmed by medical records and an active follow-up until March 31, 2023. We calculated three dietary indices: the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). Cox proportional hazards regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of plant-based indices with lung cancer mortality. During the follow-up period (median: 40.97 months; interquartile: 29.77-45.63 months), 240 patients died from lung cancer. An inverse association was observed between hPDI scores and lung cancer mortality (Q4 vs. Q1, HR, 0.66, 95% CI, 0.45-0.97, the P value for trend, 0.042), while each 10-unit increment was associated with a decreased risk of lung cancer mortality (HR, 0.75; 95% CI, 0.57-0.99). Regarding PDI and uPDI, no significant association was found with lung cancer mortality. Our study suggests that adherence to a diet with a high hPDI score may reduce lung cancer mortality.

Cancer of unknown primary site in the mandibular region: A case report.

The diagnosis and treatment of cancer of unknown primary site (CUP) present with difficulties and produce a poor prognosis. The current study presents the case of a patient with CUP in the mandibular region was treated with docetaxel and lobaplatin chemotherapy, and vascular embolization of the tumor. The tumor size was markedly reduced and the patient's quality of life improved following radiotherapy. The present case report is accompanied by a discussion of the literature to contextualize the treatment regimen for patients with CUP. These findings will support current treatment practices, inform oncologists and benefit patients with cancer.

Role of iron biomarkers and iron intakes in lung cancer risk: A systematic review and meta-analysis.

BACKGROUND: The role of iron biomarkers and iron intake in the susceptibility to lung cancer is unclear. The purpose of this study was to conduct a systematic review and meta-analysis, to assess the relationship between iron levels in the body or iron intake and the risk of lung cancer. METHOD: This review is registered with PROSPERO (number CRD 42020199776). PubMed, Web of Science, Scopus, Embase and Cochrane were used to search for studies assessing the relationship between iron and lung cancer, up to July 15, 2021. Qualitative and quantitative analysis was carried out to determine if there was a correlation between iron biomarkers/intakes and the risk of lung cancer. RESULT: Twenty articles were included. Pooled analyses demonstrated that serum ferritin concentrations and transferrin saturation (TSAT) were significantly higher in patients with lung cancer than in healthy controls (ferritin: standardized mean differences [SMD], 0.235, 95% confidence interval [CI], 0.129, 0.341, I2 = 32.1 %; TSAT: SMD, 0.07, 95 % CI, 0.018, 0.121, I2 = 0 %). In contrast, serum transferrin concentrations were significantly lower in patients with lung cancer than in healthy controls (SMD, -0.591, 95 % CI, -1.18, -0.003, I2 = 87.7 %). No significant effects of serum iron, lung tissue iron, bronchoalveolar lavage fluid (BALF) ferritin, or iron intake (total iron, dietary iron, heme iron, or non-heme iron) were found on lung cancer incidence. CONCLUSION: Among the different iron biomarkers analyzed, a trend in association was only detected with serum ferritin, TSAT and transferrin concentration and no associations were found between iron intakes and the risk of lung cancer. However, more prospective studies are needed to strengthen the current evidence.

In situ insertion of copper to form heteroanionic D3h-symmetric [Cu3Mo8O32]10- for a templated Ag55 nanocluster.

A polyoxometalate-templated thiolate-protected silver nanocluster, [Cu3(Mo4O16)2@Ag55(CyhS)43(CH3O)(COOCF3)]·3H2O, has been isolated under solvothermal conditions. In situ insertion of three Cu2+ ions into two polymolybdate anions generated a new, sandwich-type D3h-symmetric [Cu3(Mo4O16)2]10- polyoxoanion template encapsulated into an Ag55(CyhS)43 shell. The structure and composition of this Ag nanocluster have been fully characterized. This work has provided a new way to develop high-nuclearity metal nanoclusters with various structures.

[Estimating average tree height in Xixiaoshan Forest Farm, Northeast China based on Sentinel-1 with Sentinel-2A data]. / 基于Sentinel-1和Sentinel-2Açš„è¥¿å°å±±æž—åœºå¹³å‡æ ‘é«˜ä¼°æµ‹.

Forest resource survey is important for the sustainable development of forest ecosystem in China. The average tree height is a main structural parameter of forest resource survey, and also one of the key parameters with greatest difficulty to obtain. The purpose of this study was to explore the potential of joint active and passive remote sensing technology in estimating forest average height. Taking Xixiaoshan Forest Farm in Linjiang City of Jilin Province as the research area, we used Sentinel-1 SAR and Sentinel-2A data, extracted two backscatter coefficients and eight texture information of Sentinel-1, ten spectral bands and texture information of Sentinel-2A and eleven vegetation index variables, constructed five groups of average tree height estimation models based on above variables and fusion of four variables by multiple linear regression method. We further evaluated the influence of each variable on the inversion accuracy. The results showed that the texture information extracted from the Sentinel-2A spectral band of a single data source variable had a better modeling effect and could be used as effective data to estimate the average tree height. The height estimation model of the integrated four variables was optimal, with a R2 vaule of 0.56, a root mean square error of leave-one-out cross-validation of 2.92 m, and a relative root mean square error of leave-one-out cross-validation of 21.5%. The forest average height model based on Sentinel-1 and Sentinel-2a characteristic variables could improve the estimation accuracy of forest height, which could be used for regional forest average height estimation and mapping.

Blue luminescent N,S-doped carbon dots encapsulated in red emissive Eu-MOF to form dually emissive composite for reversible anti-counterfeit ink.

Lanthanide metal-organic frameworks (Ln-MOFs) have demonstrated great potential in luminescence sensing and optical anti-counterfeiting. High-security anti-counterfeiting technology is of great importance and requires the development of universal luminescent materials with multiple modes of emission and adjustable photoluminescence. Herein, a 3D red light emission microporous europium(iii) metal-organic framework [Eu3(OH)(1,3-db)2(H2O)4]·3H2O (1) (1,3-db = 1,3-di(3',5'-dicarboxylpheny) benzene) was constructed from a zigzag [Eu3(COO)8] chain and π-electron-rich terphenyl-tetracarboxylate. Notably, the quenched fluorescence of 1 under hydrogen chloride vapor could be recovered upon fuming by a vapor of Et3N. Most strikingly, the strong blue light emission by nitrogen and sulfur co-doped carbon dots (N,S-CDs) could be encapsulated in 1 to generate a dual-emission composite, namely, N,S-CDs@Eu-MOF, which shows solvent-dependent photoluminescence: N,S-CD-related blue luminescence in water and Eu-MOF-related red emission in organic solvents. Taking advantage of the above unique reversible fluorescent behavior, Eu-MOF and N,S-CDs@Eu-MOF are prepared as fluorescent high-security inks to achieve data encryption and decryption on specific flower patterns.

Evaluate the effectiveness of breast cancer decision aids: A systematic review and meta-analysis of randomize clinical trails.

AIM: To assess the effectiveness of decision aids in the treatment, prevention and screening of breast cancer patients. DESIGN: A systematic review and meta-analysis. METHODS: The review protocol was registered in the CRD Prospero database(CRD42020173028). A literature search was carried out in five databases: PubMed, Cochrane, EMBASE, Scopus and Web of science data in January 2020. We used The Cochrane risk bias assessment tool to evaluate the literature quality of included trials and the Review Manager 5.2 software to analyse data. RESULTS: We included 22 studies. Compared with the conventional methods, decision aids reduced treatment decision conflicts and had no significant effect on screening decision conflicts (WMD=-2.25, 95% CI = - 2.64,-1.87, p < .0001; WMD=-1.37, 95% CI = - 3.57,0.83, p = .22). Three were no statistical differences in participants' anxiety, decision regret, knowledge, informed choice and decision-making satisfaction between the two groups.

Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19).

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.

Unveiling the relative stability and proton binding of non-classical Wells-Dawson isomers of [(NaF6)W18O54(OH)2]7- and [(SbO6)W18O54(OH)2]9-: a DFT study.

Density functional theory calculations combined with the energy and building-block decomposition analyses have been carried out to investigate the structures, stability orders, redox potentials and proton binding of the six Baker-Figgis isomers (α, ß, γ, α*, ß* and γ*) of [(SbO6)W18O54(OH)2]9- {H2SbW18} and [(NaF6)W18O54(OH)2]7- {H2NaW18} anions at the level of PBEsol-D3/TZP. Both bonding energy and Gibbs free energy analyses exhibit that the two non-classical Wells-Dawson (WD) species behave quite differently from each other. The pyroanimonate {H2SbW18}, with a stability order of γ* > ß* > α > α* > ß > γ, is a non-classical WD species, while the hexafluoride {H2NaW18} (α > ß > γ > γ* > ß* > α*) is a transition intermediate between classical and non-classical WD types, possessing both non-classical ([XW18O60(OH)2]n-, X = I, Te and W) and classical [Si2W18O62]8- properties. Energy decomposition analyses (EDA) reveal that spatial arrangement (Ehost), host-guest fragment interaction energy (FIE), and structural distortion energy (DE) are three key factors governing the relative stability of isomers; among these, DE is always dominant, while FIE and Ehost are subordinated but are still important. Building-block decomposition analyses (BDA) disclose that the octahedral {MO6} units of the equatorial belt, particularly the staggered belt, are always more distorted than those of the two polar caps inside each structure. The theoretical redox potentials demonstrate that the oxidizing power increases with a trend of α < ß < γ and α* < ß* < γ* for both species, and the first redox potential is closely related to the energy level of the LUMO of each anion. Evaluation of the proton inclusion energies suggests that {H2NaW18} can only embed two protons, while {H2SbW18} may encapsulate four; the number of embedded protons is controlled by both the charge of the heteroatom X and the volume of the tetrahedral {O4}/{OF3} cavity.

Variation at HLA-DPB1 is associated with dermatomyositis in Chinese population.

Dermatomyositis (DM) is a polygenic disorder characterized by inflammation of skeletal muscle and skin. To date, the exact etiopathogenesis of DM remains elusive. To explore the genetic basis of DM, we conducted genome-wide genotyping analysis of 127 patients and 1566 healthy controls by Illumina Human OmniZhongHua-8 BeadChips in the Chinese Han population. We investigated whether the three SNP (rs7750458, rs9501251 and rs9500928) at 6p21.32 in the HLA-DPB1 gene were significantly associated with DM (P < 5 × 10-8 ) and identified two susceptibility loci at 7q34 (PIP, rs9986765, P = 7.45 × 10-7 , odds ratio [OR] = 2.71) and 10q24.2 (CPN1, rs3750716, P = 9.04 × 10-7 , OR = 4.39) with suggestive evidence. We imputed 6674 classical human leukocyte antigen (HLA) alleles, amino acids and SNP from the discovery dataset, and stepwise analysis revealed that HLA-DPB1*17 in class II HLA genes were significantly associated with DM susceptibility. This study represents the first genome-wide association study (GWAS) of DM in the Chinese Han population. For the first time, HLA-DPB1 was found to be associated with DM in this population. Moreover, we identified two novel suggestive susceptibility loci (PIP and CPN1) and confirmed four previously reported genes (DMB, DQA1, DQB1 and DRB1) having potential associations with DM in the Chinese Han population. Our GWAS results in this population should provide important information regarding the genetic etiopathogenesis of DM and facilitate the development of new therapies for the treatment of DM and the prevention of DM progression.

Association analyses confirm five susceptibility loci for systemic lupus erythematosus in the Han Chinese population.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Currently, numerous genetic loci of SLE have been confirmed. Here we try to further explore additional genes contributing to SLE susceptibility in this study. METHODS: Forty nine single nucleotide polymorphisms (SNPs) with moderate-risk for SLE in previous study were genotyped in a large-scale replication study with a total of 3,522 cases and 8,252 controls using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate through PLINK 1.07 software. RESULTS: This replication effort confirmed five reported SLE susceptibility loci reaching genome-wide levels of significance (P(meta) <5.00 × 10(-08)): TNFSF4 (rs1418190, odds ratio (OR) = 0.81, P(meta) = 1.08 × 10(-08); rs4916219, OR = 0.80, P(meta )= 7.77 × 10(-09)), IRF8 (rs2934498, OR = 1.25, P(meta) = 4.97 × 10(-09)), miR-146a (rs2431697, OR = 0.69, P(meta) = 1.15 × 10(-22)), CD44 (rs2732547, OR = 0.82, P(meta) = 1.55 × 10(-11)), and TMEM39A (rs12494314, OR = 0.84, P(meta) = 1.01 × 10(-09)). Further logistic regression analysis indicated that the genetic effects within TNFSF4 detected in this study are independent from our previously reported signals. CONCLUSIONS: This study increases the number of established susceptibility loci for SLE in Han Chinese population and highlights the contribution of multiple variants of modest effect. Although further studies will be required to identify the causal alleles within these loci, the findings make a significant step forward in our understanding of the genetic contribution to SLE in Chinese population.

Identification of a missense variant in LNPEP that confers psoriasis risk.

Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our genome-wide association study data set of 1,139 cases and 2,234 controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10(-13), odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10(-11)P9.37 × 10(-5)), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly downregulated in psoriatic lesions compared with the control skin (P=1.44 × 10(-6)) and uninvolved patient skin (P=2.95 × 10(-4)). Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also has a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into psoriasis pathogenesis with the involvement of the renin-angiotensin system pathway.

Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population.

Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.

Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population.

BACKGROUND: Genome-wide association studies (GWASs) have revealed a large number of genetic risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE), share susceptibility loci. Our study explores additional susceptibility loci shared by psoriasis and SLE in the Chinese Han population. METHODS: In total, 20 single nucleotide polymorphisms (SNPs) in 17 previously reported psoriasis susceptibility loci and 34 SNPs from 24 previously reported SLE susceptibility loci were investigated in our initial psoriasis and SLE GWAS dataset. Among these SNPs, we selected two SNPs (rs8016947 and rs4649203) with association values of p<5×10(-2) for both diseases in the GWAS data for further investigation in psoriasis (7260 cases and 9842 controls) and SLE (2207 cases and 9842 controls) using a Sequenom MassARRAY system. RESULTS: We found that these two SNPs (rs8016947 and rs4649203) in two loci (NFKBIA and IL28RA) were associated with psoriasis and SLE with genome-wide significance (Pcombined<5×10(-8) in psoriasis and Pcombined<5×10(-8) in SLE): rs8016947 at NFKBIA (Pcombined-psoriasis=3.90×10(-10), Pcombined-SLE=1.08×10(-13)) and rs4649203 at IL28RA (Pcombined-psoriasis=3.91×10(-12), Pcombined-SLE=9.90×10(-9)). CONCLUSIONS: These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.

Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly inherited epidermal keratinization disorder whose etiology remains unclear. We performed exome sequencing in one unaffected and two affected individuals from a DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene located in previously defined linkage regions after filtering against existing SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into consideration the functional implications of the mutations. Sanger sequencing in 57 individuals with familial DSAP and 25 individuals with sporadic DSAP identified MVK mutations in 33% and 16% of these individuals (cases), respectively. All 14 MVK mutations identified in our study were absent in 676 individuals without DSAP. Our functional studies in cultured primary keratinocytes suggest that MVK has a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation. Our results should help advance the understanding of DSAP pathogenesis.

Association analysis of single nucleotide polymorphisms at five loci: comparison between atopic dermatitis and asthma in the Chinese Han population.

Atopic diseases, such as atopic dermatitis (AD) and asthma, are closely related to clinical phenotypes with hypersensitivity, and often share some similar genetic and pathogenic bases. Our recent GWAS identified three susceptibility gene/loci FLG (rs11204971 and rs3126085), 5q22.1 (rs10067777, rs7701890, rs13360927 and rs13361382) and 20q13.33 (rs6010620) to AD. The effect of these AD associated polymorphisms in asthma is so far unknown. To investigate whether AD relevant genetic variants is identical to asthma and reveal the differences in genetic factors between AD and asthma in Chinese Han population, seven AD associated single nucleotide polymorphisms (SNPs) as well as 3 other SNPs (rs7936562 and rs7124842 at 11q13.5 and rs4982958 at 14q11.2) from our previous AD GWAS were genotyped in 463 asthma patients and 985 controls using Sequenom MassArray system. We found rs4982958 at 14q11.2 was significantly associated with asthma (P = 3.04×10(-4), OR = 0.73). We also detected one significant risk haplotype GGGA from the 4 SNPs (rs10067777, rs7701890, rs13360927 and rs13361382) at 5q22.1 in AD cases (P(correction) = 3.60×10(-10), OR = 1.26), and the haplotype was suggestive of risk in asthma cases in this study (P = 0.014, P(correction) = 0.084, OR = 1.38). These SNPs (rs11204971, rs3126085, rs7936562, rs712484 and rs6010620) at AD susceptibility genes/loci FLG, 11q13.5 and 20q13.33 were not associated with asthma in this study. Our results further comfirmed that 14q11.2 was an important candidate locus for asthma and demonstrated that 5q22.1 might be shared by AD and asthma in Chinese Han population.

Follow-up study identifies two novel susceptibility loci PRKCB and 8p11.21 for systemic lupus erythematosus.

OBJECTIVE: We have performed a large-scale replication study based on our previous genome-wide association study (GWAS) of SLE in the Chinese Han population to further explore additional genetic variants affecting susceptibility to SLE. METHODS: Thirty-eight single nucleotide polymorphisms from our GWAS were genotyped in two additional Chinese Han cohorts (total 3152 cases and 7050 controls) using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate. RESULTS: Association evidence for rs16972959 (PRKCB at 16p11.2) and rs12676482 (8p11.21) with SLE was replicated independently in both replication cohorts (P < 0.05), showing high significance for SLE in combined all 4199 cases and 8255 controls of Chinese Han [rs16972959: odds ratio (OR) = 0.81; 95% CI 0.76, 0.87; P(combined) = 1.35 × 10(-9); rs12676482: OR = 1.26; 95% CI 1.15, 1.38; P(combined) = 6.68 × 10(-7)). PRKCB is related to the established SLE immune-related pathway (NF-κB) and 8p11.21 contains important candidate genes such as IKBKB and DKK4. IKBKB is a critical component of NF-κB and DKK4 is an inhibitor of canonical Wnt signalling pathway. Interestingly, PRKCB is required for recruiting IKBKB into lipid rafts, up-regulating NF-κB-dependent survival signal. CONCLUSIONS: Our findings provided novel insights into the genetic architecture of SLE and emphasized the contribution of multiple variants of modest effect. Further study focused on PRKCB, 8p11.21, should advance our understanding on the pathogenesis of SLE.

[µ-4-Benzoyl-1-(1-oxido-2-naphthyl-carbon-yl)thio-semicarbazidato(4-)]bis-[pyridine-copper(II)].

In the title dinuclear complex, [Cu(2)(C(19)H(11)N(3)O(3)S)(C(5)H(5)N)(2)], the two Cu(II) centers have different coordination environments, viz. N(2)OS and N(2)O(2), each exhibiting a distorted square-planar geometry. π-π inter-actions between the aromatic rings of neighbouring complexes [centroid-centroid distance = 3.856 (5) Å] link pairs of mol-ecules into centrosymmetric dimers, which are further packed into stacks along the b axis with relatively short Cu⋯Cu separations of 3.482 (1) Å. Weak inter-molecular C-H⋯N hydrogen bonds help to consolidate the crystal packing.