Superconductivity in an infinite-layer nickelate.

The discovery of unconventional superconductivity in (La,Ba)2CuO4 (ref. 1) has motivated the study of compounds with similar crystal and electronic structure, with the aim of finding additional superconductors and understanding the origins of copper oxide superconductivity. Isostructural examples include bulk superconducting Sr2RuO4 (ref. 2) and surface-electron-doped Sr2IrO4, which exhibits spectroscopic signatures consistent with a superconducting gap3,4, although a zero-resistance state has not yet been observed. This approach has also led to the theoretical investigation of nickelates5,6, as well as thin-film heterostructures designed to host superconductivity. One such structure is the LaAlO3/LaNiO3 superlattice7-9, which has been recently proposed for the creation of an artificially layered nickelate heterostructure with a singly occupied [Formula: see text] band. The absence of superconductivity observed in previous related experiments has been attributed, at least in part, to incomplete polarization of the eg orbitals10. Here we report the observation of superconductivity in an infinite-layer nickelate that is isostructural to infinite-layer copper oxides11-13. Using soft-chemistry topotactic reduction14-20, NdNiO2 and Nd0.8Sr0.2NiO2 single-crystal thin films are synthesized by reducing the perovskite precursor phase. Whereas NdNiO2 exhibits a resistive upturn at low temperature, measurements of the resistivity, critical current density and magnetic-field response of Nd0.8Sr0.2NiO2 indicate a superconducting transition temperature of about 9 to 15 kelvin. Because this compound is a member of a series of reduced layered nickelate crystal structures21-23, these results suggest the possibility of a family of nickelate superconductors analogous to copper oxides24 and pnictides25.

Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8+ T cell-mediated antitumour immunity and improves anti-PD-1 efficacy.

OBJECTIVE: The gain of function (GOF) CTNNB1 mutations (CTNNB1 GOF ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 GOF HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC. DESIGN: RNA sequencing was performed to identify the key downstream genes of CTNNB1 GOF associated with immune escape. An in vitro coculture system, murine subcutaneous or orthotopic models, spontaneously tumourigenic models in conditional gene-knock-out mice and flow cytometry were used to explore the biological function of matrix metallopeptidase 9 (MMP9) in tumour progression and immune escape. Single-cell RNA sequencing and proteomics were used to gain insight into the underlying mechanisms of MMP9. RESULTS: MMP9 was significantly upregulated in CTNNB1 GOF HCC. MMP9 suppressed infiltration and cytotoxicity of CD8+ T cells, which was critical for CTNNB1 GOF to drive the suppressive tumour immune microenvironment (TIME) and anti-PD-1 resistance. Mechanistically, CTNNB1 GOF downregulated sirtuin 2 (SIRT2), resulting in promotion of ß-catenin/lysine demethylase 4D (KDM4D) complex formation that fostered the transcriptional activation of MMP9. The secretion of MMP9 from HCC mediated slingshot protein phosphatase 1 (SSH1) shedding from CD8+ T cells, leading to the inhibition of C-X-C motif chemokine receptor 3 (CXCR3)-mediated intracellular of G protein-coupled receptors signalling. Additionally, MMP9 blockade remodelled the TIME and potentiated the sensitivity of anti-PD-1 therapy in HCC. CONCLUSIONS: CTNNB1 GOF induces a suppressive TIME by activating secretion of MMP9. Targeting MMP9 reshapes TIME and potentiates anti-PD-1 efficacy in CTNNB1 GOF HCC.

Resolving the polar interface of infinite-layer nickelate thin films.

Nickel-based superconductors provide a long-awaited experimental platform to explore possible cuprate-like superconductivity. Despite similar crystal structure and d electron filling, however, superconductivity in nickelates has thus far only been stabilized in thin-film geometry, raising questions about the polar interface between substrate and thin film. Here we conduct a detailed experimental and theoretical study of the prototypical interface between Nd1-xSrxNiO2 and SrTiO3. Atomic-resolution electron energy loss spectroscopy in the scanning transmission electron microscope reveals the formation of a single intermediate Nd(Ti,Ni)O3 layer. Density functional theory calculations with a Hubbard U term show how the observed structure alleviates the polar discontinuity. We explore the effects of oxygen occupancy, hole doping and cation structure to disentangle the contributions of each for reducing interface charge density. Resolving the non-trivial interface structure will be instructive for future synthesis of nickelate films on other substrates and in vertical heterostructures.

Doping evolution of the Mott-Hubbard landscape in infinite-layer nickelates.

The recent observation of superconductivity in [Formula: see text] has raised fundamental questions about the hierarchy of the underlying electronic structure. Calculations suggest that this system falls in the Mott-Hubbard regime, rather than the charge-transfer configuration of other nickel oxides and the superconducting cuprates. Here, we use state-of-the-art, locally resolved electron energy-loss spectroscopy to directly probe the Mott-Hubbard character of [Formula: see text] Upon doping, we observe emergent hybridization reminiscent of the Zhang-Rice singlet via the oxygen-projected states, modification of the Nd 5d states, and the systematic evolution of Ni 3d hybridization and filling. These experimental data provide direct evidence for the multiband electronic structure of the superconducting infinite-layer nickelates, particularly via the effects of hole doping on not only the oxygen but also nickel and rare-earth bands.

UPLC/Q-TOF-MS-based metabolomics and molecular docking analysis of Bifidobacterium adolescentis exposure to levofloxacin.

Antibiotic-associated diarrhea is a common adverse reaction caused by the widespread use of antibiotics. The decrease in probiotics is one of the reasons why antibiotics cause drug-induced diarrhea. However, few studies have addressed the intrinsic mechanism of antibiotics inhibiting probiotics. To investigate the underlying mechanism of levofloxacin against Bifidobacterium adolescentis, we used a metabolomics mass spectrometry-based approach and molecular docking analysis for a levofloxacin-induced B. adolescentis injury model. The results showed that levofloxacin reduced the survival rate of B. adolescentis and decreased the number of B. adolescentis. The untargeted metabolomics analysis identified 27 potential biomarkers, and many of these metabolites are involved in energy metabolism, amino acid metabolism and the lipid metabolism pathway. Molecular docking showed that levofloxacin can bind with aminoacyl-tRNA synthetase and lactic acid dehydrogenase. This result provides a novel insight into the mechanism of the adverse reactions of levofloxacin.

Spontaneous regression of an isolated retinal astrocytic hamartoma in a newborn: a case report.

BACKGROUND: To report the spontaneous regression of an isolated retinal astrocytic hamartoma in a newborn. During the seven-month follow-up duration, fundus photography and fluorescein angiography examinations were performed. CASE PRESENTATION: An isolated retinal astrocytic hamartoma was detected in the nasal retina of the left eye of a 4-day-old male infant. At the time of initial presentation, we detected a solitary yellowish-white flat mass with an approximate size of 1.5 disc diameters in the nasal retina. Fluorescein angiography (FA) revealed a diffuse hyperfluorescence with slight fluorescence leakage. Seven months later, the fundus examination showed no lesion in the left eye, FA revealed mild tortuous vessels without leakage. CONCLUSIONS: In the present case, we established that the isolated retinal astrocytic hamartoma in this infant has underwent spontaneous regression. This case can point out that follow -up reexaminations are advisable for a solitary yellowish-white flat mass of the fundus in a newborn.

Efficacy and Safety of Ticagrelor versus Aspirin and Clopidogrel for Stroke Prevention in Patients with Vascular Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors. METHODS: The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I2 statistics to assess statistical heterogeneity. RESULTS: This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81-0.99, p = 0.03; I2 = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74-0.90, p < 0.0001; I2 = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84-1.06, p = 0.31; I2 = 62%), major bleeding (OR: 1.06; 95% CI: 0.97-1.15, p = 0.20; I2 = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76-1.96, p = 0.41; I2 = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78-1.43, p = 0.71; I2 = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19-1.66, p < 0.0001; I2 = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75-0.93, p = 0.0009; I2 = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71-0.89, p < 0.0001; I2 = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes. CONCLUSION: Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.

Propagule size and seed development duration: high photosynthate allocation and growth allometry.

MAIN CONCLUSION: The divergences in propagule mass have been more consistently associated with divergences in seed development duration or fruit pedicel cross-sectional area than with divergences in any other biotic factors. Allometry and Corner's rule became an important theme in evolutionary biology of plant trait structure and function. Being one of the most widely noticed plant traits, propagule (seed and fruit) mass variation mechanism across species is still controversial. Here we examined correlations between propagule mass and seed development duration as well as other traits, such as cross-sectional area of fruit pedicel, life form, fruit type and leaf area over four census years, to test an important life history strategy for propagule biomass allocation. We investigated 491 species, belonging to 91 families and 320 genera, representing 95% of native wild species in Beijing Botanical Garden. The scaling correlations between propagule mass and seed development duration and the other traits were determined using phylogenetic generalized linear models. Results show a significant positive relationship among propagule mass and seed development duration, leaf area and pedicel cross-sectional area for all species and for each life form (except vines) regardless of phylogeny. The variation in seed mass has been more consistently associated with variation in seed development duration than with divergences in any other variable, such as growth form, fruit type, pedicel cross-sectional area and leaf area, whereas variation in fruit weight was found to be more associated with variation in pedicel cross-sectional area than the other. Biotic factors, such as seed development duration, pedicel cross-sectional area, growth form and leaf area, mediate propagule size variation, of which seed development duration or pedicel cross-sectional area is the most important. The results further supported a hypothesis that large-seeded species evolved owing to high photosynthate availability and growth allometry in plant body. A mechanistic mathematical model involving seed development duration was provided to expound propagule mass variations across species.

Application of the Modified Basic Life Support Training Model in Improving Community Residents' Rescue Willingness in Nantong City in China.

Objective: This study explores the application and effect of the modified basic life support training in improving the first-aid level and rescue willingness of community residents in China. Methods: A total of 94 residents of a community in Nantong city were selected as the subjects by cluster sampling to receive the modified basic life support (BLS) training. The BLS knowledge, attitudes, and behaviors of all recruited subjects were evaluated by a questionnaire before and after training. A skill operation assessment was used to evaluate the effectiveness of the modified BLS training. Results: There were statistically significant differences in the BLS rescue willingness, theory, and skill scores before and after the training (P < 0.01). A total of 93.62% of the residents considered the modified BLS training model easier to learn and acceptable than the traditional model, and 92.55% of them thought the training content and teaching arrangement were reasonable. Conclusion: The modified BLS training model could improve the community residents' rescue willingness and skill mastery rates, enhance their first-aid skills and awareness, reduce the risk of disease transmission to a certain extent, and improve the success rate of prehospital first aid to ensure the safety of rescuers and patients.

Stabilization of Sr3Al2O6 Growth Templates for Ex Situ Synthesis of Freestanding Crystalline Oxide Membranes.

A new synthetic approach has recently been developed for the fabrication of freestanding crystalline perovskite oxide nanomembranes, which involves the epitaxial growth of a water-soluble sacrificial layer. By utilizing an ultrathin capping layer of SrTiO3, here we show that this sacrificial layer, as grown by pulsed laser deposition, can be stabilized in air and therefore be used as transferrable templates for ex situ epitaxial growth using other techniques. We find that the stability of these templates depends on the thickness of the capping layer. On these templates, freestanding superconducting SrTiO3 membranes were synthesized ex situ using molecular beam epitaxy, enabled by the lower growth temperature which preserves the sacrificial layer. This study paves the way for the synthesis of an expanded selection of freestanding oxide membranes and heterostructures with a wide variety of ex situ growth techniques.

Spontaneous Strain Buffer Enables Superior Cycling Stability in Single-Crystal Nickel-Rich NCM Cathode.

The capacity degredation in layered Ni-rich LiNixCoyMnzO2 (x ≥ 0.8) cathode largely originated from drastic surface reactions and intergranular cracks in polycrystalline particles. Herein, we report a highly stable single-crystal LiNi0.83Co0.12Mn0.05O2 cathode material, which can deliver a high specific capacity (∼209 mAh g-1 at 0.1 C, 2.8-4.3 V) and meanwhile display excellent cycling stability (>96% retention for 100 cycles and >93% for 200 cycles). By a combination of in situ X-ray diffraction and in situ pair distribution function analysis, an intermediate monoclinic distortion and irregular H3 stack are revealed in the single crystals upon charging-discharging processes. These structural changes might be driven by unique Li-intercalation kinetics in single crystals, which enables an additional strain buffer to reduce the cracks and thereby ensure the high cycling stability.

Value of Xpert MTB/RIF Using Bronchoalveolar Lavage Fluid for the Diagnosis of Pulmonary Tuberculosis: a Systematic Review and Meta-analysis.

The performance of Xpert MTB/RIF using bronchoalveolar lavage fluid (BAL) for the diagnosis of pulmonary tuberculosis (PTB) remains unclear. Therefore, a systematic review/meta-analysis was conducted. Studies published before 31 December 2019 were retrieved from the PubMed, Embase, and Web of Science databases using the keywords "pulmonary tuberculosis," "Xpert MTB/RIF," and "BAL." Two independent evaluators extracted the data and assessed the bias risk of the included studies. A random-effects model was used to calculate the overall sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR), and the area under the curve (AUC), as well as the respective 95% confidence intervals (CIs). Nineteen trials involving 3,019 participants met the inclusion criteria. Compared to the culture method, the pooled sensitivity, specificity, PLR, NLR, DOR, and the AUC with 95% CIs of Xpert MTB/RIF were 0.87 (0.84 to 0.90), 0.92 (0.91 to 0.93), 10.21 (5.78 to 18.02), 0.16 (0.12 to 0.22), 78.95 (38.59 to 161.53), and 0.9467 (0.9462 to 0.9472), respectively. Relative to the composite reference standard, the observed values were 0.69 (0.65 to 0.72), 0.98 (0.98 to 0.99), 37.50 (18.59 to 75.62), 0.30 (0.21 to 0.43), 171.98 (80.82 to 365.96), and 0.9691 (0.9683 to 0.9699), respectively. All subgroups, except children, showed high sensitivity and specificity. In conclusion, the use of Xpert MTB/RIF in the context of BAL samples has a high diagnostic performance for PTB (except for children) and may serve as an alternative rapid diagnostic tool.

A Superconducting Praseodymium Nickelate with Infinite Layer Structure.

A variety of nickel oxide compounds have long been studied for their manifestation of various correlated electron phenomena. Recently, superconductivity was observed in nanoscale infinite layer nickelate thin films of Nd0.8Sr0.2NiO2, epitaxially stabilized on SrTiO3 substrates via topotactic reduction from the perovskite precursor phase. Here, we present the synthesis and properties of PrNiO2 thin films on SrTiO3. Upon doping in Pr0.8Sr0.2NiO2, we observe superconductivity with a transition temperature of 7-12 K and robust critical current density at 2 K of 334 kA/cm2. These findings indicate that superconductivity in the infinite layer nickelates is relatively insensitive to the details of the rare earth 4f configuration. Furthermore, they motivate the exploration of a broader family of compounds based on two-dimensional NiO2 planes, which will enable systematic investigation of the superconducting and normal state properties and their underlying mechanisms.

Use of thiazide diuretics for the prevention of recurrent kidney calculi: a systematic review and meta-analysis.

BACKGROUND: Thiazide diuretics reduce the risk of recurrent kidney calculi in patients with kidney calculi or hypercalciuria. However, whether thiazide diuretics can definitely prevent recurrent kidney calculi remains unclear. We aimed to evaluate the effect and safety of thiazide diuretics on recurrent kidney calculi. METHODS: The PubMed, Cochrane Library, and EMBASE databases were systematically searched using the keywords thiazide diuretics and kidney calculi to identify randomized controlled trials (RCTs). The primary outcome was the incidence of recurrent kidney calculi, and the secondary outcome was the 24-h urinary calcium level. The pooled risk ratio (RR), risk difference (RD), standardized mean difference (SMD), and 95% confidence interval (CI) were calculated. The evidence quality was graded using the GRADE criteria, and recommendations for recurrent kidney calculus prevention using thiazide diuretics were reassessed. RESULTS: Eight RCTs involving 571 patients were included. The pooled RR for the incidence of kidney calculi in the thiazide diuretic groups was 0.44 (95% CI 0.33-0.58, P < 0.0001) compared to that in the placebo and untreated groups; the pooled RD was - 0.23 (95% CI - 0.30 to - 0.16, P < 0.0001). The pooled SMD for the 24-h urinary calcium level was - 18.59 (95% CI - 25.11 to - 12.08, P < 0.0001). The thiazide diuretic groups had a high incidence of adverse reactions and low tolerance. The evidence quality for decrease in kidney calculus incidence using thiazide diuretics was low, while that for the 24-h urinary calcium level decrease among those with recurrent kidney calculi was moderate, and that for the decrease in kidney calculus incidence using short-acting and long-acting thiazide diuretics was low. The overall strength of recommendation for prevention of recurrent renal calculi using thiazide diuretics was not recommended. The subgroup and sensitivity analysis findings were robust. CONCLUSIONS: Long-term use of thiazide diuretics reduces the incidence of recurrent renal calculi and 24-h urinary calcium level. However, the benefits are insufficient, and the evidence quality is low. Considering the adverse effects, poor patient compliance, and economic burden of long-term medication, their use in preventing recurrent kidney calculi is not recommended.

Superconducting Dome in Nd_{1-x}Sr_{x}NiO_{2} Infinite Layer Films.

We report the phase diagram of Nd_{1-x}Sr_{x}NiO_{2} infinite layer thin films grown on SrTiO_{3}. A superconducting dome spanning 0.125

The potential role of sucrose transport gene expression in the photosynthetic and yield response of rice cultivars to future CO2 concentration.

The metabolic basis for observed differences in the yield response of rice to projected carbon dioxide concentrations (CO2 ) is unclear. In this study, three rice cultivars, differing in their yield response to elevated CO2 , were grown under ambient and elevated CO2 conditions, using the free-air CO2 enrichment technology. Flag leaves of rice were used to determine (1) if manipulative increases in sink strength decreased the soluble sucrose concentration for the 'weak' responders and (2), whether the genetic expression of sucrose transporters OsSUT1 and OsSUT2 was associated with an accumulation of soluble sugars and the maintenance of photosynthetic capacity. For the cultivars that showed a weak response to additional CO2 , photosynthetic capacity declined under elevated CO2 and was associated with an accumulation of soluble sugars. For these cultivars, increasing sink relative to source strength did not increase photosynthesis and no change in OsSUT1 or OsSUT2 expression was observed. In contrast, the 'strong' response cultivar did not show an increase in soluble sugars or a decline in photosynthesis but demonstrated significant increases in OsSUT1 and OsSUT2 expression at elevated CO2 . Overall, these data suggest that the expression of the sucrose transport genes OsSUT1 and OsSUT2 may be associated with the maintenance of photosynthetic capacity of the flag leaf during grain fill; and, potentially, greater yield response of rice as atmospheric CO2 increases.

The psychological typhoon eye effect during the COVID-19 outbreak in China: the role of coping efficacy and perceived threat.

BACKGROUND: The influence of COVID-19 on mental health problems has received considerable attention. However, only a few studies have examined the relationship between exposure to COVID-19 and mental health problems, and no empirical study has tested the mechanisms between them. METHODS: We conducted a survey in 31 provinces of China during 3-13 March 2020 to test the effect of the exposure level on mental health problems. Our sample comprised 2987 participants who reported their perceived threat, coping efficacy, mental health problems and other demographic variables. Multiple mediators path analysis was used in the data analysis. RESULTS: The results showed that the level of exposure to COVID-19 in China was negatively associated with mental health problems, which confirmed the "Psychological Typhoon Eye" effect. Further analyses indicated that both perceived threat and coping efficacy partially mediated the relationship between them. However, coping efficacy explained the "Psychological Typhoon Eye" effect. Perceived threat mediated the positive relationship between exposure level and mental health problems. CONCLUSION: This study detected the psychological typhoon eye effect and demonstrated the mediating role of coping efficacy and perceived threat between exposure to COVID-19 and mental health problems. Our findings suggest that policy makers and psychological workers should provide enough psychological services to low-risk areas as the high-risk areas. An important means of alleviating mental health problems is to improve coping efficacy.

Role of glycine on sulfuric acid-ammonia clusters formation: Transporter or participator.

Glycine (Gly) is ubiquitous in the atmosphere and plays a vital role in new particle formation (NPF). However, the potential mechanism of its on sulfuric acid (SA) - ammonia (A) clusters formation under various atmospheric conditions is still ambiguous. Herein, a (Gly)x·(SA)y·(A)z (z ≤ x + y ≤ 3) multicomponent system was investigated by using density functional theory (DFT) combined with Atmospheric Cluster Dynamics Code (ACDC) at different temperatures and precursor concentrations. The results show that Gly, with one carboxyl (-COOH) and one amine (-NH2) group, can interact strongly with SA and A in two directions through hydrogen bonds or proton transfer. Within the relevant range of atmospheric concentrations, Gly can enhance the formation rate of SA-A-based clusters, especially at low temperature, low [SA], and median [A]. The enhancement (R) of Gly on NPF can be up to 340 at T = 218.15 K, [SA] = 104, [A] = 109, and [Gly] = 107 molecules/cm3. In addition, the main growth paths of clusters show that Gly molecules participate into cluster formation in the initial stage and eventually leave the cluster by evaporation in subsequent cluster growth at low [Gly], it acts as an important "transporter" to connect the smaller and larger cluster. With the increase of [Gly], it acts as a "participator" directly participating in NPF.

A case-control study of selenoprotein genes polymorphisms and autoimmune thyroid diseases in a Chinese population.

BACKGROUND: Selenium is an essential trace and there is a high selenium concentration in the thyroid gland. Selenium deficiency may impair the thyroid function. The aim of this study was to investigate the association between three selenoprotein genes polymorphisms and autoimmune thyroid diseases. METHODS: We genotyped six single-nucleotide polymorphisms (SNPs), rs6865453 in selenoprotein P gene (SELENOP), rs713041 rs2074451 rs3746165 in glutathione peroxidase 4 gene (GPX4) and rs28665122 and rs7178239 in selenoprotein S gene (SELENOS) by MassARRAY system using the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry technology in 1060 patients with autoimmune thyroid diseases and 938 healthy controls. RESULTS: Major alleles in rs6865453 of SELENOP, rs713041, rs2074451, rs3746165 of GPX4 decreased while the major allele C in rs28665122 of SELENOS increased in AITD patients than in the control. The allele C and genotype CC in rs7178239 of SELENOS showed different trend in GD and HT patients when compared with the control. All the distribution difference showed nonsignificant. Analysis according to clinical features including ophthalmopathy, hypothyroidism and family history came out to be negative either. CONCLUSIONS: Our findings suggest non-association between three selenoprotein genes and AITD, conflicting to the positive result in another population. Different selenium nutrition status in different populations may contribute to conflicting results, the contribution of genetic variants in AITD mechanism may be another reason.

MiR-34a contributes to diabetes-related cochlear hair cell apoptosis via SIRT1/HIF-1α signaling.

Type 2 diabetes (T2DM) has been considered to be associated with a higher likelihood of hearing impairment (HI). However, the molecular mechanisms underlying the association between diabetes and HI are poorly understood. MicroRNAs have recently been demonstrated to be closely associated with hearing loss and considered as promising therapeutic targets. Herein, we investigated whether miR-34a contributes to diabetes-related cochlear hair cell apoptosis and sought to identify the underlying mechanism. The results showed that miR-34a was up-regulated in the cochleas of db/db mice, accompanied by significant hearing threshold elevation and hair cell loss. However, the expression of SIRT1 was significantly down-regulated, while hypoxia-inducible factor-1alpha (HIF-1α) levels were dramatically increased in the cochleas of db/db mice. In addition, in the high-glucose cultured House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line, miR-34a overexpression inhibited sirtuin1 (SIRT1) expression, increased HIF-1α levels and promoted apoptosis. MiR-34a knockdown exerted effects that were diametrically opposed to those observed with overexpression. Interestingly, HIF-1α knockdown almost eliminated the cell apoptosis induced by high glucose levels. We also examined the modulation of HIF-1α expression by SIRT1. The results showed that SIRT1 knockdown further promoted high-glucose-induced HIF-1α expression, while SIRT1 overexpression significantly inhibited HIF-1α level induced by high glucose. These findings point to a new mechanism by which miR-34a exerts its detrimental effects by negatively regulating SIRT1/HIF-1α signaling and provide new therapeutic targets for treating hearing impairment during diabetes.