Hydrazone-Linked Covalent Organic Frameworks.

Hydrazone-linked covalent organic frameworks (COFs) with structural flexibility, heteroatomic sites, post-modification ability and high hydrolytic stability have attracted great attention from scientific community. Hydrazone-linked COFs, as a subclass of Schiff-base COFs, was firstly reported in 2011 by Yaghi's group and later witnessed prosperous development in various aspects. Their adjustable structures, precise pore channels and plentiful heteroatomic sites of hydrazone-linked structures possess much potential in diverse applications, for example, adsorption/separation, chemical sensing, catalysis and energy storage, etc. Up to date, the systematic reviews about the reported hydrazone-linked COFs are still rare. Therefore, in this review, we will summarize their preparation methods, characteristics and related applications, and discuss the opportunity or challenge of hydrazone-linked COFs. We hope this review could provide new insights about hydrazone-linked COFs for exploring more appealing functions or applications.

Construction of Zr-Metal-Organic Frameworks-Based Composite Materials toward Anhydrous Proton Conduction and Photocatalytic CO2 Reduction.

Metal-organic frameworks constructed from Zr usually possess excellent chemical and physical stability. Therefore, they have become attractive platforms in various fields. In this work, two families of hybrid materials based on ZrSQU have been designed and synthesized, named Im@ZrSQU and Cu@ZrSQU, respectively. Im@ZrSQU was prepared through the impregnation method and employed for proton conduction. Im@ZrSQU exhibited terrific proton conduction performance in an anhydrous environment, with the highest proton conduction value of 3.6 × 10-2 S cm-1 at 110 °C. In addition, Cu@ZrSQU was synthesized via the photoinduction method for the photoreduction of CO2, which successfully promoted the conversion of CO2 into CO and achieved the CO generation rate of up to 12.4 µmol g-1 h-1. The photocatalytic performance of Cu@ZrSQU is derived from the synergistic effect of Cu NPs and ZrSQU. Based on an in-depth study and discussion toward ZrSQU, we provide a versatile platform with applications in the field of proton conduction and photocatalysis, which will guide researchers in their further studies.

A porous Ti-based metal-organic framework for CO2 photoreduction and imidazole-dependent anhydrous proton conduction.

The anhydrous proton conductivity of Im@IEF-11 resulting from the integration of imidazole and porous IEF-11 has been investigated, and the highest proton conductive value can reach up to 7.64 × 10-2 S cm-1. Furthermore, IEF-11 is also developed to reduce CO2 due to its reasonable structure and suitable energy band, and its CO formation rate is 31.86 µmol g-1 h-1.

Ag Nanoparticle-Modified Polyoxometalate-Based Metal-Organic Framework for Enhanced CO2 Photoreduction.

The photoreduction deposition method is employed to fabricate a family of silver nanoparticle (Ag NP)-modified polyoxometalate-based metal-organic framework (NENU-5) photocatalysts, named Ag/NENU-5. The title photocatalysts, Ag/NENU-5, can be used for the photocatalytic reduction of CO2 and are observed to efficiently reduce CO2 into CO, in which the highest reduction rate is 22.28 µmol g-1 h-1, 3 times greater than that of NENU-5. Photocatalytic reduction performances of CO2 have been extremely improved after the incorporation of Ag NPs as the cocatalyst. The enhancement of the photocatalytic reduction of CO2 has been attributed to the synergistic effects of Ag NPs and NENU-5, inhibiting the charge recombination during the photocatalytic process and increasing the reaction active sites. Furthermore, the influence of Ag NPs on the photocatalytic activity has also been investigated. The experimental results clearly reveal that the size of Ag NPs could exert a main effect on the photocatalytic activity, and the reasonable size of Ag NPs is able to enhance the photocatalytic reduction activity toward CO2 significantly.

A multifunctional anionic metal-organic framework for high proton conductivity and photoreduction of CO2 induced by cation exchange.

Metal-organic frameworks (MOFs) provide an ideal platform for loading various guests owing to their available space, and can be developed as a class of multifunctional materials. Herein, we cover the design and synthesis of two kinds of exchanged frameworks with multifunctional applications based on H3ImDC and In(NO3)3·2H2O through guest exchange inside the framework. The guest ammonium ion (NH4+) and [Ru(2,2'-bipyridine)3]2+ (Rubpy) are selected to exchange the dimethylammonium cation (Me2NH2+) encapsulated within In-MOF, giving birth to two kinds of new MOFs, named NH4+@In-MOF and Rubpy@In-MOF respectively. The proton conduction of NH4+@In-MOF and the CO2 photoreduction of Rubpy@In-MOF are investigated. Under different test conditions, the proton conductive behaviors of NH4+@In-MOF are evaluated and the best proton conductive value can reach up to 9.81 × 10-3 S cm-1. Compared to the original In-MOF, Rubpy@In-MOF exhibits a significantly enhanced CO2 photoreduction performance under a pure CO2 atmosphere. Furthermore, its photocatalytic activity is retained even under a 10% CO2 gas atmosphere, displaying a synergistic effect between Rubpy and In-MOF24 within Rubpy@In-MOF.

Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma.

Background: The immune landscape, prognostic model, and molecular variations of mantle cell lymphoma (MCL) remain unclear. Hence, an integrated bioinformatics analysis of MCL datasets is required for the development of immunotherapy and the optimization of targeted therapies. Methods: Data were obtained from the Gene Expression Omnibus (GEO) database (GSE32018, GSE45717 and GSE93291). The differentially expressed immune-related genes were selected, and the hub genes were screened by three machine learning algorithms, followed by enrichment and correlation analyses. Next, MCL molecular clusters based on the hub genes were identified by K-Means clustering, the probably approximately correct (PAC) algorithm, and principal component analysis (PCA). The landscape of immune cell infiltration and immune checkpoint molecules in distinct clusters was explored by single-sample gene-set enrichment analysis (ssGSEA) as well as the CIBERSORT and xCell algorithms. The prognostic genes and prognostic risk score model for MCL clusters were identified by least absolute shrinkage and selection operator (LASSO)-Cox analysis and cross-validation for lambda. Correlation analysis was performed to explore the correlation between the screened prognostic genes and immune cells or immune checkpoint molecules. Results: Four immune-related hub genes (CD247, CD3E, CD4, and GATA3) were screened in MCL, mainly enriched in the T-cell receptor signaling pathway. Based on the hub genes, two MCL molecular clusters were recognized. The cluster 2 group had a significantly worse overall survival (OS), with down-regulated hub genes, and a variety of activated immune effector cells declined. The majority of immune checkpoint molecules had also decreased. An efficient prognostic model was established, including six prognostic genes (LGALS2, LAMP3, ICOS, FCAMR, IGFBP4, and C1QA) differentially expressed between two MCL clusters. Patients with a higher risk score in the prognostic model had a poor prognosis. Furthermore, most types of immune cells and a range of immune checkpoint molecules were positively correlated with the prognostic genes. Conclusions: Our study identified distinct molecular clusters based on the immune-related hub genes, and showed that the prognostic model affected the prognosis of MCL patients. These hub genes, modulated immune cells, and immune checkpoint molecules might be involved in oncogenesis and could be potential prognostic biomarkers in MCL.

Compelling Evidence Linking CD40 Gene With Graves' Disease in the Chinese Han Population.

Mutations in CD40 have been widely reported to be risk factors for Graves' disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorphism (SNP) of CD40, and has been confirmed to predispose those with the alteration to GD, regardless of ethnicity. Our genome-wide association study (GWAS) indicated that several SNPs, including rs1883832 located within the vicinity of CD40 were associated with GD in the Han Chinese population. Aiming at identifying the most consequential SNP and its underlying pathogenic mechanism, we performed a two-stage refined study on 8,171 patients with GD and 7,906 controls, and found rs1883832 was the most significantly GD-associated SNP in the CD40 gene region (PCombined = 9.17×10-11, OR = 1.18). Through searching the cis-expression quantitative trait locus database and using quantitative RT-PCR, we further discovered that the rs1883832 genotype can influence CD40 gene transcription. Furthermore, we demonstrated that rs1883832 is a susceptibility locus for pTRAb+ GD patients. In conclusion, the current study provides robust evidence that rs1883832 can regulate CD40 gene expression and affect serum TRAb levels, which ultimately contributes to the development of GD.

Pre-Consultation System Based on the Artificial Intelligence Has a Better Diagnostic Performance Than the Physicians in the Outpatient Department of Pediatrics.

Artificial intelligence (AI) has been deeply applied in the medical field and has shown broad application prospects. Pre-consultation system is an important supplement to the traditional face-to-face consultation. The combination of the AI and the pre-consultation system can help to raise the efficiency of the clinical work. However, it is still challenging for the AI to analyze and process the complicated electronic health record (EHR) data. Our pre-consultation system uses an automated natural language processing (NLP) system to communicate with the patients through the mobile terminals, applying the deep learning (DL) techniques to extract the symptomatic information, and finally outputs the structured electronic medical records. From November 2019 to May 2020, a total of 2,648 pediatric patients used our model to provide their medical history and get the primary diagnosis before visiting the physicians in the outpatient department of the Shanghai Children's Medical Center. Our task is to evaluate the ability of the AI and doctors to obtain the primary diagnosis and to analyze the effect of the consistency between the medical history described by our model and the physicians on the diagnostic performance. The results showed that if we do not consider whether the medical history recorded by the AI and doctors was consistent or not, our model performed worse compared to the physicians and had a lower average F1 score (0.825 vs. 0.912). However, when the chief complaint or the history of present illness described by the AI and doctors was consistent, our model had a higher average F1 score and was closer to the doctors. Finally, when the AI had the same diagnostic conditions with doctors, our model achieved a higher average F1 score (0.931) compared to the physicians (0.92). This study demonstrated that our model could obtain a more structured medical history and had a good diagnostic logic, which would help to improve the diagnostic accuracy of the outpatient doctors and reduce the misdiagnosis and missed diagnosis. But, our model still needs a good deal of training to obtain more accurate symptomatic information.

Integration of zirconium-based metal-organic framework with CdS for enhanced photocatalytic conversion of CO2 to CO.

It is a promising strategy to prepare composite photocatalysts based on MOFs and semiconductors for enhancing photocatalytic reduction of carbon dioxide (CO2). A family of binary composite photocatalysts (CdS@UiO-66-NH2) with different CdS contents have been designed and synthesized, which have been explored for photocatalytic reduction of CO2. CdS@UiO-66-NH2 can efficiently convert CO2 into CO under visible light irradiation via the solid-gas mode in the absence of sacrificial agents and photosensitizers. The generation rate of CO can reach up to 280.5 µmol g-1 h-1, which is 2.13-fold and 2.9-fold improvements over the pristine CdS and UiO-66-NH2, respectively, and the selectivity for CO is very high. Furthermore, this kind of photocatalysts can still maintain great photocatalytic activity in CO2/N2 mixed atmosphere with different CO2 concentrations. The outstanding performances of CdS@UiO-66-NH2 may be attributed to the existence of the direct Z-scheme heterojunction, which possesses the enhanced separation and migration of photo-generated charge carriers between UiO-66-NH2 and CdS, available specific surface areas and improved visible light absorption ability as well as abundant reaction active sites. This case reveals that MOF-based composite photocatalysts exhibit promising potential applications in the field of CO2 conversion.

Do foreign direct investment and environmental regulation improve green technology innovation? An empirical analysis based on panel data from the Chinese manufacturing industry.

The environmental regulation and foreign direct investment (FDI) inflow have an important impact on the progress of green technology. This study analyzes the impacts of environmental regulation and FDI on green technology innovation (GTI) based on the panel data of 13 Chinese manufacturing sectors. The results of static panel regression show that the environmental regulation has a positive impact on GTI, while the FDI has a negative impact. The results of the panel threshold model reveal that the effect of environmental regulation on GTI presents a nonlinear shape. The negative effect of FDI on GTI is strengthened when the environmental regulation exceeds its threshold. Increasing FDI inflow can inhibit the effect of environmental regulation. Meanwhile, a strict environmental regulation can enhance the inhibiting effect of FDI on GTI. The FDI inflow into high-tech manufacturing sectors has a less negative impact on GTI than the FDI inflow into low-tech sectors in the case of the enhancement of environmental regulation. This study provides some implications for the formulation of environmental regulation and the FDI inflow into China to improve the GTI.

Self-assembly of TiO2/ZIF-8 nanocomposites for varied photocatalytic CO2 reduction with H2O vapor induced by different synthetic methods.

Photoreduction of carbon dioxide (CO2) provides an effective perspective for solving the energy crisis and environmental problems. Herein, two types of composite photocatalysts (TiO2/ZIF-8) based on ZIF-8 and TiO2 have been designed and synthesized with the help of the grinding method and the solid-synthesis method. Both composite photocatalysts are employed for the photocatalytic reduction of CO2. In composite photocatalysts prepared by the grinding method, ZIF-8 particles are distributed on the surface of TiO2, and provide extra available spaces for storing CO2, which is beneficial for improving their photoreduction performances. As a result, an enhanced CO formation rate of 21.74 µmol g-1 h-1 with a high selectivity of 99% is obtained for this family of composite photocatalysts via the solid-gas mode without photosensitizers and sacrificial agents. For comparison, the other family of composite photocatalysts synthesized via the solid-synthesis method possesses structures similar to ZIF-8, where TiO2 is encapsulated inside the framework of ZIF-8. This structural feature obstructs the contact between the active sites of TiO2 and CO2, and leads to lower activities. The best CO formation rate of this family is only 10.67 µmol g-1 h-1 with 90% selectivity. Both the structural features of the two families of photocatalysts are described to explain their differences in photoreduction performances. The experimental finding reveals that different synthetic approaches indeed result in diversified structures and varied photocatalytic performances. This work affords a new scalable and efficient approach for the rational design of efficient photocatalysts in the area of artificial photosynthesis.

Penfluridol triggers mitochondrial-mediated apoptosis and suppresses glycolysis in colorectal cancer cells through down-regulating hexokinase-2.

Penfluridol, a commonly used antipsychotic agent in a clinical setting, exhibits potential anticancer properties against various human malignancies. Here, we investigated the effect of penfluridol on the biological behavior of colorectal cancer (CRC) cells. Cell viability and clonogenic potential were detected by the cell counting kit-8 and colony formation assay. The cell apoptosis and cell cycle distribution were quantified through flow cytometry. Caspase-3 activity, glucose consumption, lactate production, and intracellular ATP levels were evaluated using the corresponding commercial detection kits. The protein levels of related genes were detected through western blotting. Mitochondrial membrane potential was detected using JC-1 staining. A CRC xenograft tumor model was used to validate the antitumor activity of penfluridol in vivo. Penfluridol reduced cell survival and promoted apoptotic cell death effectively through the mitochondria-mediated intrinsic pathway in a dose-dependent manner. Furthermore, the process of glycolysis in HCT-116 and HT-29 cells was inhibited upon penfluridol treatment, as evidenced by the decrease in glucose consumption, lactate production, and intracellular ATP levels. Further mechanistic studies revealed that penfluridol influenced cell apoptosis and glycolysis in CRC cells by downregulating hexokinase-2 (HK-2). The proapoptotic effect and glycolytic inhibition-induced by penfluridol were effectively reversed by HK-2 overexpression. Consistent with in vitro results, penfluridol could also suppress tumor growth and trigger apoptosis in vivo. Penfluridol triggers mitochondrial-mediated apoptosis and induces glycolysis inhibition via modulating HK-2 in CRC and provides a theoretical basis to support penfluridol as a repurposed drug for CRC patients.

Effects of Sirt3­autophagy and resveratrol activation on myocardial hypertrophy and energy metabolism.

The aim of the present study was to examine the role of sirtuin 3 (Sirt3)­autophagy in regulating myocardial energy metabolism and inhibiting myocardial hypertrophy in angiotensin (Ang) II­induced myocardial cell hypertrophy. The primary cultured myocardial cells of neonatal Sprague Dawley rats were used to construct a myocardial hypertrophy model induced with Ang II. Following the activation of Sirt3 by resveratrol (Res), Sirt3 was silenced using small interfering (si)RNA­Sirt3, and the morphology of the myocardial cells was observed under an optical microscope. Reverse transcription­polymerase chain reaction was used to detect the mRNA expression of the following myocardial hypertrophy markers; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), Sirt3, medium­chain acyl­CoA dehydrogenase (MCAD) and pyruvate kinase (PK). Western blot analysis was used to detect the protein expression of Sirt3, light chain 3 (LC3) and Beclin1. Ang II may inhibit the protein expression of Sirt3, LC3 and Beclin1. Res, an agonist of Sirt3, may promote the protein expression of Sirt3, LC3 and Beclin1. Res inhibited the mRNA expression of ANP and BNP, and reversed the Ang II­induced myocardial cell hypertrophy. The addition of siRNA­Sirt3 decreased the protein expression of Sirt3, LC3 and Beclin1, increased the mRNA expression of ANP and BNP, and weakened the inhibitory effect of Res on myocardial cell hypertrophy. Res promoted the mRNA expression of MCAD, inhibited the mRNA expression of PK, and reversed the influence of Ang II on myocardial energy metabolism. siRNA­Sirt3 intervention significantly decreased the effect of Res in eliminating abnormal myocardial energy metabolism. In conclusion, Sirt3 may inhibit Ang II­induced myocardial hypertrophy and reverse the Ang II­caused abnormal myocardial energy metabolism through activation of autophagy.

[Acupuncture ameliorates negative emotion in PCOS patients: a randomized controlled trial].

OBJECTIVE: To evaluate the effectiveness and possible mechanism of acupuncture treatment for negative emotion in patients with polycystic ovary syndrome (PCOS). METHODS: A total of 40 PCOS patients were randomly divided into an observation group and a control group, 20 cases in each one. Both groups received lifestyle interventions (exercise and diet guidance) on the 5th day of menstruation. On the basis of above treatment, the patients in the observation group received acupuncture at Guanyuan (CV 4), Zhongwan (CV 12), Guilai (ST 29), Futu (ST 32), Liangqiu (ST 34), Sanyinjiao (SP 6), Zusanli (ST 36), Hegu (LI 4), Shenmen (HT 7), Baihui (GV 20) as the main acupoints, and connected the electroacupuncture (continuous wave, 2 Hz, 30 min), once every other day, 3 times a week. The treatment for 1 month was as one course and 4 courses were required totally in both groups. Before and after treatment, the body mass index (BMI), ferriman-gallway (F-G) score, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score, PCOS health-related quality of life questionnaire (PCOSQ) score were observed, meanwhile, serum sex hormone, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progestin (P), prolactin (PRL), testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) levels, and serumß-endorphin levels were detected. RESULTS: Compared with before treatment, the BMI, F-G score, SAS score, SDS score and serum FAI level were decreased and the PCOSQ score and the levels of serum SHBG andß-endorphin were increased in the observation group after treatment (all P<0.05). Compared with before treatment, the SDS score was decreased in the control group after treatment (P<0.05). Compared with the control group, the F-G score, SDS score, SAS score, and serum FAI level were lower, and the PCOSQ score and serumß-endorphin level were higher in the observation group after treatment (all P<0.05). CONCLUSION: Applying acupuncture to the treatment of patients with PCOS can effectively relieve anxiety and depression, and the mechanism may be related to the regulation on the levels of serumß-endorphin and androgen.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients.

BACKGROUND: Coronary artery calcification (CAC) is common in end-stage renal disease (ESRD) patients, and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients. Cartilage oligomeric matrix protein (COMP), as a component of the vascular matrix, has been found to be an inhibitor of arterial calcification in basic studies. However, there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis (MHD) patients. The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients. METHODS: Serum COMP levels were compared between 54 MHD patients and 66 healthy people. MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events (MACEs), which were defined as a combined end point of new onset angina pectoris, nonfatal myocardial infarction, heart failure, coronary artery revascularization, hospitalization due to angina pectoris and all-cause deaths. The CAC score was calculated based on computed tomography scans. RESULTS: The serum COMP level in MHD patients was significantly higher than that in the general population [984.23 (248.43-1902.61) ng/mL vs. 219.01 (97.26-821.92) ng/mL, P < 0.01]. Serum COMP levels were positively correlated with CAC (r = 0.313, P = 0.021) and serum parathyroid hormone in MHD patients (r = 0.359, P < 0.01). Linear regression suggested that after adjusting for age, fasting blood glucose (Glu) and glycosylated hemoglobin (HbAlc), CAC score was an independent predictor in the final model for COMP level (ß = 0.424, t = 3.130, P < 0.01). The receiver operating characteristic (ROC) curve showed that COMP ≥ 994 mg/mL had 68.0% sensitivity and 72.4% specificity for the prediction of severe CAC [area under the curve (AUC): 0.674, P = 0.030, 95% CI: 0.526-0.882]. After a median follow-up of 16 months (8-24 months), there was no difference in the incidence rate of MACEs between the upper, middle and lower serum COMP groups. CONCLUSIONS: Our study found that MHD patients have higher levels of circulating COMP than controls. The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients. However, there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

Degradation of azo dyes under visible light with stable MOF based on tetrastyrene imidazole ligand.

In the present work, a new 3D metal-organic framework (MOF) has been synthesized and characterized. The MOF exhibits good chemical stability in aqueous solutions with the pH scale ranging from 3 to 11. Interestingly, the MOF shows high catalytic activities for the degradation of azo dyes (MO, CR and CBR) under visible light without H2O2. The Ea values of the MOF for MO, CR and CBR degradation are obtained to be 23.49, 52.68 and 15.19 kJ mol-1, respectively. In addition, the MOF can be reused in the catalytic process without the catalytic activity decreasing obviously.

Polyoxometalate-based metallogels as anode materials for lithium ion batteries.

A series of polyoxometalate (POM)-based metallogels have been synthesized, which combine both the advantages of POMs and metallogels. Notably, POM-based metallogels are employed as anode materials for the first time, and the optimized sample exhibits high reversible capacity (658 mA h g-1), high rate capability, and good cycling stability.

Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective: To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants: This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures: Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results: A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified: DCHS2 on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729: OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance: These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.

A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease.

OBJECTIVE: We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. DESIGN: Dense mapping studies based on GWAS. PATIENTS: A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. MEASUREMENTS: Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. RESULTS: After the first replication stage, four SNPs from three regions with Pfirst  < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined  = 7.55 × 10-11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined  = 5.59 × 10-8 , OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. CONCLUSIONS: Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.

Polyoxometalate-Based Metal-Organic Frameworks with Conductive Polypyrrole for Supercapacitors.

Metal-organic frameworks (MOFs) with high porosity could act as an ideal substitute for supercapacitors, but their poor electrical conductivities limit their electrochemical performances. In order to overcome this problem, conductive polypyrrole (PPy) has been introduced and a novel nanocomposite resulting from polyoxometalate (POM)-based MOFs (NENU-5) and PPy has been reported. It comprises the merits of POMs, MOFs, and PPy. Finally, the highly conductive PPy covering the surfaces of NENU-5 nanocrystallines can effectively improve the electron/ion transfer among NENU-5 nanocrystallines. The optimized NENU-5/PPy nanocomposite (the volume of Py is 0.15 mL) exhibits high specific capacitance (5147 mF·cm-2), larger than that of pristine NENU-5 (432 mF·cm-2). Furthermore, a symmetric supercapacitor device based on a NENU-5/PPy-0.15 nanocomposite possesses an excellent areal capacitance of 1879 mF·cm-2, which is far above other MOF-based supercapacitors.