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1.
Opt Express ; 29(6): 8160-8170, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820267

RESUMO

We propose a metasurface-based Lithium Niobate waveguide power splitter with an ultrabroadband and polarization independent performance. The design consists of an array of amorphous silicon nanoantennas that partially converts the input mode to multiple output modes creating multimode interference such that the input power is equally split and directed to two branching waveguides. FDTD simulation results show that the power splitter operates with low insertion loss (< 1dB) over a bandwidth of approximately 800 nm in the near-infrared range, far exceeding the O, E, S, C, L and U optical communication bands. The metasurface is ultracompact with a total length of 2.7 µm. The power splitter demonstrates a power imbalance of less than 0.16 dB for both fundamental TE and TM modes. Our simulations show that the device efficiency exhibits high tolerance to possible fabrication imperfections.

2.
Opt Express ; 29(20): 31408-31417, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615233

RESUMO

Elucidation of the underlying physics for laser-induced periodic surface structures (LIPSSs) is of great importance for their controllable fabrication. We here demonstrate a periodic structure transition from normal to anomalous morphology, upon femtosecond laser irradiation on 50-nm thick Cr/Si films in an air pressure-tunable chamber. As the air pressure gradually decreases, the amount of surface oxide induced by preceding laser pulses is found to reduce, and eventually triggering the structure evolution from the anomalously oriented subwavelength to normally oriented deep-subwavelength LIPSSs. The intriguing structure transition is explained in terms of the competitive excitation between the transverse-electric scattered surface wave and transverse-magnetic hybrid plasmon wave, which is ruled by the thickness of the preformed oxide layer indeed.

3.
Small ; 16(25): e2000733, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32410334

RESUMO

Organolead trihalide perovskites have attracted significant attention for optoelectronic applications due to their excellent physical properties in the past decade. Generally, both grain boundaries in perovskite films and the device structure play key roles in determining the device performance, especially for horizontal-structured device. Here, the first optimized vertical-structured photodetector with the perovskite single crystal MAPbBr3 as the light absorber and graphene as the transport layer is shown. The hybrid device combines strong photoabsorption characteristics of perovskite and high carrier mobility of flexible graphene, exhibits excellent photoresponse performance with high photoresponsivity (≈1017.1 A W-1 ) and high photodetectivity (≈2.02 × 1013 Jones) in a low light intensity (0.66 mW cm-2 ) under the actuations of 3 V bias and laser irradiation at 532 nm. In particular, an ultrahigh photoconductive gain of ≈2.37 × 103 is attained because of fast charge transfer in the graphene and large recombination lifetime in the perovskite single crystal. The vertical architecture combining perovskite crystal with highly conductive graphene offers opportunities to fulfill the synergistic effect of perovskite and 2D materials, is thus promising for developing high-performance electronic and optoelectronic devices.

4.
Med Sci Monit ; 26: e918972, 2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31982890

RESUMO

BACKGROUND Whether type 2 diabetes mellitus (T2DM) is independently associated with structural heart abnormalities is controversial because of confounders associated with T2DM. This study aimed to investigate echocardiographic features in patients with newly diagnosed T2DM, exploring changes in cardiac structure and function. MATERIAL AND METHODS This was a retrospective study of new T2DM cases treated at the Second People's Hospital Affiliated to Nanjing Medical University (Changzhou) in 2014-2016. In all, 128 T2DM cases were included (62 hypertensive and 66 non-hypertensive individuals). Controls were selected among individuals who underwent examination at the same department/period. Interventricular septal thickness (IVST), left ventricular end-diastolic diameter (LVEDD), posterior left ventricular wall thickness (PWTD), left ventricle mass (LVM), end-diastolic thickness of left ventricular posterior wall (Dd), aortic root diameter, left atrial diameter (LAd), left atrial diameter fraction-shortening values, and left ventricular ejection fraction (LVEF) were determined routinely. RESULTS IVST, LVEDD, PWTD, Dd, LAd, and left atrial diameter fraction-shortening values were larger in patients with T2DM (all P<0.05 vs. controls). LVM was higher in T2DM patients (median, 57.12 vs. 54.77 g, P=0.001). There were no differences in aortic root diameter and EF (both P>0.05). Multivariable analysis showed that IVST (OR=1.33, 95% CI: 1.01-1.76, P=0.04), LAd (OR=1.16, 95% CI: 1.07-1.25, P<0.001), TGs (OR=1.34, 95% CI: 1.09-1.63, P=0.005), and HDL (OR=1.46, 95% CI: 1.02-2.08, P=0.04) were independently associated with hypertension in patients with T2DM. CONCLUSIONS Patients with newly diagnosed T2DM already display structural heart abnormalities. LAd and IVST are independently associated with hypertension in these patients, probably contributing to increased cardiovascular risk.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Ecocardiografia , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada
5.
Phys Rev Lett ; 122(4): 047401, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768350

RESUMO

For centrosymmetric materials such as monolayer graphene, no optical second-harmonic generation (SHG) is generally expected, because it is forbidden under the electric-dipole approximation. Yet we observe a strong, doping-induced SHG from graphene, with its highest strength comparable to the electric-dipole-allowed SHG in noncentrosymmetric 2D materials. This novel SHG has the nature of an electric-quadrupole response, arising from the effective breaking of inversion symmetry by optical dressing with an in-plane photon wave vector. More remarkably, the SHG is widely tuned by carrier doping or chemical potential, being sharply enhanced at Fermi-edge resonances but vanishing at the charge neutral point that manifests the electron-hole symmetry of massless Dirac fermions. This striking behavior in graphene, which should also arise in graphenelike Dirac materials, expands the scope of nonlinear optics and holds the promise of novel optoelectronic and photonic applications.

6.
Diabetes Obes Metab ; 21(4): 939-948, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30520221

RESUMO

AIMS: To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy. MATERIALS AND METHODS: In this 48-week, multi-centre, open-label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c <7.0%, without hypoglycaemia, defined as blood glucose <3.9 mmol/L and weight gain <3.0% after 48 weeks of treatment. RESULTS: Over 48 weeks, a greater proportion of patients achieved the primary endpoint with saxagliptin compared with glimepiride (43.3% vs 31.3%; odds ratio, 1.38, 95% CI, 1.05-1.82; P = 0.019), especially among patients with baseline HbA1c <8.0%, duration <5 years or baseline BMI ≥25 kg/m2 . Mean reduction in HbA1c was similar in the two treatment groups at Week 48 (-0.94% with saxagliptin vs -0.98% with glimepiride; P = 0.439). Bodyweight decreased with saxagliptin, but increased with glimepiride over the treatment period, and the treatment difference was -1.6 kg (P < 0.001) at Week 48. The proportion of patients experiencing hypoglycaemia was much lower with saxagliptin vs glimepiride (3.1% vs 12.8%; P < 0.001). CONCLUSIONS: This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes.


Assuntos
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adamantano/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Aumento de Peso
7.
Cell Physiol Biochem ; 49(5): 1804-1812, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30231244

RESUMO

BACKGROUND/AIMS: Microbes reside in a number of body sites, including the oral cavity, and are associated with the progression of many systemic diseases. In this study, we aimed to investigate the effects of gout and hyperuricemia (HUA) on the composition of oral microbiomes. METHODS: Analysis of the oral microbiota from 12 gout patients, 11 HUA patients, and 19 healthy control subjects was performed using a deep sequencing approach, and validation of significant changes in Prevotella intermedia and Serratia marcescens in new patient cohorts was performed using quantitative PCR (qPCR). RESULTS: Our analysis indicated that both gout and HUA significantly altered the composition of the oral microbiome in patients. Patients with gout or HUA had significantly greater levels of salivary Prevotella intermedia but significantly lower levels of Serratia marcescens than healthy control subjects. CONCLUSION: We demonstrated the association between the oral microbiome and gout and HUA for the first time. In particular, 16S sequencing and qPCR analysis revealed significantly higher levels of oral Prevotella intermedia in gout/HUA patients, which suggests that these patients might be at risk for the development of periodontitis.


Assuntos
Gota/patologia , Microbiota , Boca/microbiologia , Prevotella intermedia/isolamento & purificação , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Gota/microbiologia , Humanos , Hiperuricemia/microbiologia , Hiperuricemia/patologia , Masculino , Pessoa de Meia-Idade , Prevotella intermedia/genética , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Serratia marcescens/genética , Serratia marcescens/isolamento & purificação
8.
Gen Comp Endocrinol ; 260: 25-31, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28842216

RESUMO

Insulin resistance is generally responsible for the pathogenesis of type 2 diabetes mellitus (T2DM). Early growth response proteins-2 (Egr2) has been reported to be able to increase the expression of the suppressors of cytokine signaling-1 (SOCS-1), and impair insulin signaling pathway through suppression of insulin receptor substrates (IRS), including IRS-1 and IRS-2. However, whether Egr2 is directly involved in the development of insulin resistance, and how its potential contributions to insulin resistance still remain unknown. Here, our present investigation found that the expression levels of Egr2 were up-regulated when insulin resistance occurs, and knockdown of Egr2 abolished the effect of insulin resistance in HepG2 cells induced with palmitate (PA). Importantly, inhibition of Egr2 decreased the expression of SOCS-1 as well as reduced phosphorylation of JAK2 and STAT3. And, our data indicated that silencing of Egr2 accelerated hepatic glucose uptake and reversed the impaired lipid metabolism upon insulin resistance. In summary, the present study confirms that Egr2 could deteriorate insulin resistance via the pathway of JAK2/STAT3/SOCS-1 and may shed light on resolving insulin resistance and further the pathogenesis of T2DM.


Assuntos
Proteína 2 de Resposta de Crescimento Precoce/fisiologia , Resistência à Insulina/genética , Janus Quinase 2/metabolismo , Ácido Palmítico/farmacologia , Fator de Transcrição STAT3/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Animais , Proteína 2 de Resposta de Crescimento Precoce/genética , Células Hep G2 , Humanos , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
9.
Biochem Biophys Res Commun ; 444(1): 69-74, 2014 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-24434148

RESUMO

Atherosclerosis is the main underlying cause of major cardiovascular diseases such as stroke and heart attack. Oxidized phospholipids such as oxidized 1-palmitoyl-2-arachidonoyl-sn-Glycero-3-phosphorylcholine (OxPAPC) accumulate in lesions of and promote atherosclerosis. OxPAPC activates endothelial cells, a critical early event of atherogenesis. Epoxyisoprostane E2 (EI) is an oxidized fatty acid contained at the sn-2 position of 1-palmitoyl-2-epoxyisoprostane E2-sn-glycero-3-phosphorylcholine (PEIPC), the most active component of OxPAPC in regulating inflammation. OxPAPC and its components including PEIPC activate endothelial cells to express an array of genes in different categories including oxidative stress response genes such as tumor suppressor gene OKL38 and Heme oxygenase-1 (HO-1). EI can be released by lipase from PEIPC. In this study, we examined the ability of EI to stimulate oxidative stress response in endothelial cells. EI released from OxPAPC and synthetic EI stimulated the expression of oxidative stress response gene OKL38 and antioxidant gene HO-1. Treatment of endothelial cells with EI increased the production of superoxide. NADPH oxidase inhibitor Apocynin and superoxide scavenger N-acetyl-cysteine (NAC) significantly attenuated EI-stimulated expression of OKL38 and HO-1. We further demonstrated that EI activated oxidative stress-sensitive transcription factor Nrf2. Silencing of Nrf2 with siRNA significantly reduced EI stimulated expression of OKL38 and HO-1. Thus, we demonstrated that EI induced oxidative stress in endothelial cells leading to increased expression of oxidative stress response gene OKL38 and HO-1 via Nrf2 signaling pathway relevant to atherosclerosis.


Assuntos
Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Isoprostanos/farmacologia , Proteínas Reguladoras de Apoptose , Aterosclerose/etiologia , Aterosclerose/metabolismo , Células Cultivadas , Heme Oxigenase-1/genética , Humanos , Isoprostanos/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fosfatidilcolinas/metabolismo , Fosfatidilcolinas/farmacologia , Proteínas/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
10.
Pak J Med Sci ; 30(6): 1203-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25674108

RESUMO

OBJECTIVE: To evaluate correlations between insulin secretion and resistance in patients with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). METHODS: Three hundred thirty six pregnant women with an oral glucose tolerance test (OGTT) were tested and measured insulin function indices (IFI), insulin resistance indices (HOMA-IR) as well as blood serum triglycerides (TG), total cholesterol (TCH) and low density lipoprotein cholesterol (LDL-C) concentrations. GIGT patients were further divided into subgroups according to hyperglycemia appearance 1, 2 or 3 hours after glucose ingestion. RESULTS: GDM and GIGT correlated with age (p<0.05), family history of diabetes (p<0.05) and pre-pregnancy body mass indices (BMIs) (p<0.05). Blood pressures were higher in GDM than in GIGT and normal glucose tolerance (NGT) patients (p<0.05). The IFIs were gradually reduced (p<0.05), whereas HOMA-IR was gradually enhanced (p<0.05) in the GIGT and GDM patients. Blood serum TG, TCH and LDL-C concentrations were higher in the GIGT and GDM groups (p<0.05) and the GIGT 1 hour hyperglycemia subgroup had highest pregnancy weight gain and HOMA-IR values (p<0.05). Conclusions : Advanced age, family history of diabetes, high BMIs and blood pressure were risk factors for GIGT and GDM, which were both caused by reduced insulin secretion and enhanced insulin resistance.

11.
Sci Adv ; 10(25): eadp0575, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38896626

RESUMO

Dirac fermion in topological materials exhibits intriguing nonlinear optical responses. However, their direct correlation with the linearly dispersed band remains elusive experimentally. Here, we take topological semimetal ZrSiS as a paradigm, unveiling three unique nonlinear optical signatures of Dirac fermion. These signatures include strong quadrupolar response, quantum interference effect, and exponential divergent four-wave mixing (FWM), all of which are described by the prominent third-order nonlinear optical susceptibility. Resonantly enhanced by linear bands, quadrupolar second harmonic generation in centrosymmetric bulk overwhelms the electric-dipole contribution at the surface with inherent inversion symmetry breaking. Furthermore, owing to the interference between multiple resonant transition pathways within linear bands, difference-frequency FWM is several orders of magnitude stronger than sum-frequency FWM and third harmonic generation. The difference-frequency FWM further displays an inverse-square divergence toward degenerate excitation, whose scaling law perfectly matches with the long-sought behavior of Dirac fermion. These signatures lay the solid foundation toward the practical applications of topological materials in nonlinear optoelectronics and photonics.

12.
Adv Mater ; 36(7): e2306772, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37661841

RESUMO

The vector characteristics of light and the vectorial transformations during its transmission lay a foundation for polarized photodetection of objects, which broadens the applications of related detectors in complex environments. With the breakthrough of low-dimensional materials (LDMs) in optics and electronics over the past few years, the combination of these novel LDMs and traditional working modes is expected to bring new development opportunities in this field. Here, the state-of-the-art progress of LDMs, as polarization-sensitive components in polarized photodetection and even the imaging, is the main focus, with emphasis on the relationship between traditional working principle of polarized photodetectors (PPs) and photoresponse mechanisms of LDMs. Particularly, from the view of constitutive equations, the existing works are reorganized, reclassified, and reviewed. Perspectives on the opportunities and challenges are also discussed. It is hoped that this work can provide a more general overview in the use of LDMs in this field, sorting out the way of related devices for "more than Moore" or even the "beyond Moore" research.

13.
Light Sci Appl ; 13(1): 119, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802363

RESUMO

Nonlinear optical activities, especially second harmonic generation (SHG), are key phenomena in inversion-symmetry-broken two-dimensional (2D) transition metal dichalcogenides (TMDCs). On the other hand, anisotropic nonlinear optical processes are important for unique applications in nano-nonlinear photonic devices with polarization functions, having become one of focused research topics in the field of nonlinear photonics. However, the strong nonlinearity and strong optical anisotropy do not exist simultaneously in common 2D materials. Here, we demonstrate strong second-order and third-order susceptibilities of 64 pm/V and 6.2×10-19 m2/V2, respectively, in the even-layer PdPSe, which has not been discovered in other common TMDCs (e.g., MoS2). Strikingly, it also simultaneously exhibited strong SHG anisotropy with an anisotropic ratio of ~45, which is the largest reported among all 2D materials to date, to the best of our knowledge. In addition, the SHG anisotropy ratio can be harnessed from 0.12 to 45 (375 times) by varying the excitation wavelength due to the dispersion of χ ( 2 ) values. As an illustrative example, we further demonstrate polarized SHG imaging for potential applications in crystal orientation identification and polarization-dependent spatial encoding. These findings in 2D PdPSe are promising for nonlinear nanophotonic and optoelectronic applications.

14.
J Hum Genet ; 58(3): 135-41, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23303383

RESUMO

MicroRNAs (miRNAs) negatively regulate target gene expression by binding to 3'-untranslated region of target mRNA. Single-nucleotide polymorphisms (SNPs) that reside in the miRNA target sites can affect the bindings of miRNAs to mRNAs. Compelling evidence has shown that miRNAs contribute to the etiology of type 2 diabetes (T2DM). We hypothesized that SNPs in diabetes-related miRNA target-binding sites could be associated with the risk of T2DM. We selected 10 SNPs on miRNA-binding sites by using bioinformatics software. Genotypes of T2DM patients (n=1017) and normal controls (n=1059) were analyzed by TaqMan assay. The variant genotypes rs1366600CC and TC/CC in the insulin receptor (INSR) gene, rs2292899GA in the acyl-CoA synthetase 1 (ACSL1) gene and rs11724758AA in the fatty-acid-binding protein 2 (FABP2) gene were associated with T2DM (adjusted odds ratios (ORs) (95% confidence intervals)=2.03 (1.02-4.01), 1.28 (1.04-1.57), 1.22 (1.004-1.49) and 0.76 (0.58-0.997), respectively). The analysis stratified by age, gender, waist circumstance and living habits also revealed these genotypes' effect. Furthermore, crossover analysis indicated those who exposed to both environmental factor and putative risk genotypes did have the highest risk of T2DM. A cumulative effect of SNPs rs1366600, rs2292899 and rs11724758 was observed with individuals carrying 2, 3 and 4-6 risk alleles having a gradually increased risk of T2DM (OR=1.52, 1.81 and 2.28, P for trend <0.001). Our result suggested that INSR rs1366600, ACSL1 rs2292899 and FABP2 rs11724758 could influence the susceptibility to T2DM in Chinese Han population, most likely through their effects on the specific miRNA-binding sites and functional characterizations of three genes are needed.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Antígenos CD/genética , Antígenos CD/metabolismo , Povo Asiático/genética , Sítios de Ligação , Estudos de Casos e Controles , China , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Biologia Computacional , Intervalos de Confiança , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Fatores de Risco , Circunferência da Cintura
15.
Clin Chim Acta ; 549: 117552, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37709110

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with diabetic retinopathy (DR), but effective interventions are lacking. The relationship between osteocalcin (OC) and DR in postmenopausal women with T2DM is understudied. METHODS: This study examined 950 postmenopausal women with T2DM (T2DR group: n = 299; T2DM group: n = 651). RESULTS: Significant differences (p < 0.05) were observed between the groups in disease duration, age, gender, body mass index (BMI), glycated haemoglobin (HbA1c), low-density lipoprotein (LDL-C), parathyroid hormone (PTH), total type I collagen amino acid-prolonging peptide (TPINP), OC, and 25 hydroxyvitamin D (25(OH)D3). Logistic regression revealed associations of LDL-C, PTH, and 25(OH)D3 with DR. A non-linear relationship (p < 0.05) between OC and DR was found. The lowest DR risk occurred at OC levels of 15.0-25.3 ng/ml (OR, 0.66; 95 % CI, 0.44, 0.98) compared to 11.1-15.0 ng/ml. Risk remained unchanged below 11.1 ng/ml or above 25.3 ng/ml. CONCLUSION: In conclusion, among postmenopausal women with T2DM, OC levels showed a non-linear relationship with DR. Optimal OC levels (15.0-25.3 ng/ml) were associated with minimal DR occurrence, while risk was constant below 11.1 ng/ml or above 25.3 ng/ml. Maintaining optimal OC levels may reduce DR risk in this population.

16.
J Orthop Translat ; 38: 117-125, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36381249

RESUMO

Objectives: This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 â€‹mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Results: Of the 448 randomized patients, 409 (LY06006, n â€‹= â€‹311; placebo, n â€‹= â€‹98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P â€‹< â€‹0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 â€‹N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. Conclusion: In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. The translational potential of this article: In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.

17.
Ann Hum Genet ; 76(2): 101-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22439148

RESUMO

Our aim was to investigate whether the ADIPOQ gene polymorphisms are associated with the metabolic syndrome (MetS). Genotypes of MetS patients (n=1049) and normal controls (n= 1092) were analysed by TaqMan® assay, and serum adiponectin concentration was measured by ELISA. The variant genotypes rs266729CG; rs1063539GC, GC/CC; rs16861205AA and rs7649121AT, AT/TT (Adjusted P=0.037, 0.044, 0.025, 0.011, 0.019, 0.020, respectively) of the ADIPOQ gene were associated with MetS. Patients with rs266729CG, CG/GG genotypes (P=0.034, 0.035) and rs7649121AT, AT/TT genotypes (P=0.013, 0.022) had higher levels of serum adiponectin than those with the CC and AA genotypes respectively. Furthermore, the prevalence of haplotypes GGAAAATC and GGGTAACC was lower in cases (10.7% and 4.5%) than in controls (12.1% and 5.9%) [Adjusted ORs (95% CIs)=0.70 (0.54­0.91), 0.65 (0.46­0.92)]. The ADIPOQ gene variants associated with the risk of MetS in this study must be validated by further functional studies to reveal any potential effects on metabolism.


Assuntos
Adiponectina/genética , Povo Asiático/genética , Predisposição Genética para Doença , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Adiponectina/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
Biochem Biophys Res Commun ; 428(1): 62-7, 2012 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-23058918

RESUMO

Hemagglutinin (HA) of influenza A has been reported as the key protein in viral infection. Therefore, the density and the dynamic pattern of this protein in viral envelope will affect the virus to infect target cells. We used a lentiviral system to study the influenza A H1N1 viral infection. Herein we demonstrate that the influenza non-structural proteins (NS) significantly promote viral infection. By substituting NS gene segment from an H1N1 genome set of A/WSN/1933 with the NS segment isolated from another H1N1 substrain genome set, China246, we found that viral infection tropism was significantly altered. The reassortant H1N1 shows almost identical infectivity compared with its parental virus, A/WSN/1933, for the human epithelial cell line HOT, but shows only 1/100 infectivity of its parental virus when infecting the Madin-Darby canine kidney (MDCK) cell line. These results suggest that not only is NS important in the infectivity of human influenza virus, but that it may play a critical role in viral tropism, allowing the virus to mutate and spread to other species.


Assuntos
Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/virologia , Proteínas não Estruturais Virais/fisiologia , Tropismo Viral , Animais , Células CACO-2 , Cães , Genoma Viral , HIV/química , HIV/ultraestrutura , Células HeLa , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Células Madin Darby de Rim Canino , Proteínas não Estruturais Virais/genética , Vírion/química
19.
Adv Mater ; 34(29): e2201229, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35605244

RESUMO

The direct photocurrent detection capability of light orbital angular momentum (OAM) has recently been realized with topological Weyl semimetals, but it is limited to the near-infrared wavelength range. The extension of the direct OAM detection capability to the mid-infrared band, which is a wave band that plays an important role in a vast range of applications, has not yet been realized. This is because the photocurrent responses of most photodetectors are neither sensitive to the phase information nor efficient in the mid-infrared region. In this study, a photodetector based on the type-II Weyl semimetal tantalum iridium telluride (TaIrTe4 ) is designed with peculiar electrode geometries to directly detect the topological charge of the OAM using the orbital photogalvanic effect (OPGE). The results indicate that the helical phase gradient of light can be distinguished by a current winding around the optical beam axis, with a magnitude proportional to its quantized OAM mode number. The topologically enhanced responses in the mid-infrared region of TaIrTe4 further help overcome the low responsivity issues and finally render direct OAM detection capability. This study enables on-chip-integrated OAM detection, and thus OAM-sensitive focal plane arrays in the mid-infrared region.

20.
Nat Commun ; 13(1): 1623, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338125

RESUMO

The thermoelectric effects of topological semimetals have attracted tremendous research interest because many topological semimetals are excellent thermoelectric materials and thermoelectricity serves as one of their most important potential applications. In this work, we reveal the transient photothermoelectric response of Dirac semimetallic Cd3As2, namely the photo-Seebeck effect and photo-Nernst effect, by studying the terahertz (THz) emission from the transient photocurrent induced by these effects. Our excitation polarization and power dependence confirm that the observed THz emission is due to photothermoelectric effect instead of other nonlinear optical effect. Furthermore, when a weak magnetic field (~0.4 T) is applied, the response clearly indicates an order of magnitude enhancement on transient photothermoelectric current generation compared to the photo-Seebeck effect. Such enhancement supports an ambipolar transport nature of the photo-Nernst current generation in Cd3As2. These results highlight the enhancement of thermoelectric performance can be achieved in topological Dirac semimetals based on the Nernst effect, and our transient studies pave the way for thermoelectric devices applicable for high field circumstance when nonequilibrium state matters. The large THz emission due to highly efficient photothermoelectric conversion is comparable to conventional semiconductors through optical rectification and photo-Dember effect.

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