Downregulation of microRNA-873 attenuates insulin resistance and myocardial injury in rats with gestational diabetes mellitus by upregulating IGFBP2.

Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance, and patients with GDM have a higher risk of cardiovascular disease. Multiple microRNAs (miRNAs) are reported to be involved in the regulation of myocardial injury. Moreover, miR-873 was predicted to target insulin-like growth factor binding protein 2 (IGFBP2) through bioinformatic analysis, which was further confirmed using a luciferase assay. Thus, our objective was to assess whether microRNA-873 (miR-873) affects insulin resistance and myocardial injury in an established GDM rat model. The GDM rats were treated with miR-875 mimic or inhibitor or IGFBP2 siRNA. The effects of miR-875 and IGFBP2 on the cardiac function, insulin resistance, and myocardial injury were evaluated by hemodynamic measurements, determination of biochemical indices of myocardium and serum, and insulin homeostatic model assessment. The results indicated that downregulation of miR-873 upregulated the expression of IGFBP2 and promoted the activation of phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. With downregulation of miR-873 in GDM rats, the cardiac function was improved and the myocardial apoptosis was inhibited, coupled with elevated activity of superoxide dismutase, carbon monoxide synthase, and the nitric oxide content. In addition, the inhibition of miR-873 in GDM rats modulated the insulin resistance and reduced myocardial apoptosis. Overall, the data showed that inhibition of miR-873 by targeting IGFBP2 may regulate the insulin resistance and curtail myocardial injury in GDM rats through activating the PI3K/AKT/mTOR axis, thus providing a potential means of impeding the progression of GDM.

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers.

Antibody drug conjugates (ADCs) are powerful anti-cancer therapies comprising an antibody joined to a cytotoxic payload through a chemical linker. ADCs exploit the specificity of antibodies for their target antigens, combined with the potency of cytotoxic drugs, to selectively kill target antigen-expressing tumour cells. The recent rapid advancement of the ADC field has so far yielded twelve and eight ADCs approved by the US and EU regulatory bodies, respectively. These serve as effective targeted treatments for several haematological and solid tumour types. In the development of an ADC, the judicious choice of an antibody target antigen with high expression on malignant cells but restricted expression on normal tissues and immune cells is considered crucial to achieve selectivity and potency while minimising on-target off-tumour toxicities. Aside from this paradigm, the selection of an antigen for an ADC requires consideration of several factors relating to the expression pattern and biological features of the target antigen. In this review, we discuss the attributes of antigens selected as targets for antibodies used in clinically approved ADCs for the treatment of haematological and solid malignancies. We discuss target expression, functions, and cellular kinetics, and we consider how these factors might contribute to ADC efficacy.

Synergistic Approach toward Erbium-Passivated Triple-Anion Organic-Free Perovskite Solar Cells with Excellent Performance for Agrivoltaics Application.

All-inorganic perovskite solar cells (IPSCs) have gained massive attention due to their less instability against common degradation factors (light, heat, and moisture) than their organic-inorganic hybrid counterparts. Inorganic perovskites bear a general formula of CsPbX3 (X = Cl, I, Br). The mixed halide CsPbIBr2 perovskite possesses an intermediate band gap of 2.03 eV with enhanced stability, which is still available for photovoltaic applications and the research focus of this work. We present a synergistic approach of pre-heated solution dropping with inorganic additive inclusion to deposit the organic-free triple anion CsPbIBr2 PSC. Erbium (Er)-passivated triple-anion CsI(PbBr2)0.97(ErCl3)0.03 IPSCs with inorganic carrier selective layers (CTLs), that is, organic-free, are fabricated with enhanced carrier diffusion length and crystalline grain size while lessening the grain boundaries near perovskite active layer (PAL)-bulk/carrier selective interfaces. As a result, the trap-state densities within the perovskite bulk were suppressed with stabilized CTL/PAL interfaces for smooth and enhanced carrier transportation. Therefore, for the first time, we contradict the common belief of VOC loss due to halide segregation, as a nice VOC of about 1.34 V is achieved for an organic-free IPSC through enriching initial radiative efficiency, even when halide segregation is present. The optimized organic-free IPSC yielded a power conversion efficiency of 11.61% and a stabilized power output of 10.72%, which provides the potential opportunity to integrate into agrivoltaics (AgV) projects.

Revealing the Aging Effect of Metal-Oleate Precursors on the Preparation of Highly Luminescent CsPbBr3 Nanoplatelets.

Due to the ultrafast crystallization process in the triple-source ligand-assisted reprecipitation (TSLARP) technique the [LyPbBrx] octahedra is easily distorted, resulting in anisotropic two-dimensional nanoplatelets (NPLs) with low photoluminescence quantum yield (PLQY) and poor stability. Unexpectedly, we obtain CsPbBr3 NPLs with PLQY approaching unity and high stability using the TSLARP technique through aging the metal-oleate precursors. We find that the significant enhancement of the PLQY is related to the change of solution chemistry of the Pb-oleate precursor in the aging process. While hybrid CsPbBr3@Cs4PbBr6 NPLs with low PLQY (28%) are formed with fresh Pb-oleate precursor, phase-pure CsPbBr3 NPLs with PLQY of 97.4% are obtained with the aged Pb-oleate precursor. A model that takes into account the transformation of the Pb-oleate in toluene from isolated molecules into clusters after aging is proposed to explain the phenomenon. Our finding highlights the importance of understanding the solution chemistry for the synthesis of the highly luminescent NPLs and provides a new way to break the "blue-wall" in perovskite light-emitting devices.

Ionic liquid-induced in situ deposition of perovskite quantum dot films with a photoluminescence quantum yield of over 85.

Metal halide perovskite quantum dots (QDs) hold great promise as building blocks for next-generation light emitting devices (LEDs). The preparation of perovskite QD films with high photoluminescence quantum yield (PLQY) is the key to realizing efficient LEDs. However, the conventional deposition method of spin-coating of pre-synthesized QD ink solutions results in perovskite QD films with low PLQY (typically <45%) due to non-radiative recombination centers induced in the deposition process. Here, by utilizing the ionic nature and steric hindrance effect of the ionic liquid, we demonstrate an in situ deposition method for perovskite QD films with high PLQY by directly spin-coating precursor solutions containing an ionic liquid. Furthermore, mechanistic study reveals that the ionic liquid not only induces the formation of QDs but also suppresses defect-related recombination through the interaction with uncoordinated metal atoms on the surface of the QDs. As a result, the in situ deposited CsPbBr3 QD film with a PLQY as high as 85.2% and long-term air stability is achieved. These findings demonstrate that the introduction of an ionic liquid provides an effective strategy to enhance the performance of in situ formed perovskite QD films, which could benefit the development of efficient LEDs and other optoelectronic devices.

Large-Area Organic-Free Perovskite Solar Cells with High Thermal Stability.

Organic-free perovskite solar cells (PSCs) have been considered as the most promising candidate for achieving long-term stability. Here, we demonstrate an organic-free PSC consisting of inorganic CsPbI2Br perovskite, nickel oxide hole transport layer, and niobium oxide electron transport layer. A maximum power conversion efficiency (PCE) of 11.20% is achieved with an active area of 5 cm2, and it increases to 14.11% with smaller area. More importantly, the organic-free PSCs show excellent thermal stability with PCE remaining above 98% of its initial value when heated at 100 °C for 150 min. Postannealing at a proper temperature further increases its maximum PCE to 14.45%, which is the highest among any reported all-inorganic PSCs with a p-i-n structure. The enhanced performance of the postannealed device is ascribed to the decreased trap-state density and improved interface charge-transfer properties. These results demonstrated that this novel organic-free device architecture can be employed to fabricate efficient and stable PSCs for large-scale manufacturing.

High Photovoltage Inverted Planar Heterojunction Perovskite Solar Cells with All-Inorganic Selective Contact Layers.

Inverted planar heterojunction perovskite solar cells based on all-inorganic selective contact layers show great promise for commercialization owing to their competitiveness in terms of cost and stability. However, the power conversion efficiencies (PCEs) of the few reported perovskite solar cells with this type of device structure have been limited by relatively low photovoltages. Here, we propose a new device structure comprising electron beam-evaporated nickel and niobium oxides as the hole and electron selective contact layers, respectively. We demonstrate that a metal oxide material can be directly deposited on a perovskite film by electron beam evaporation without damaging the interface. We propose that the turn-on voltage of the p-n junction formed by the selective contacts represents a quantitative proxy of the charge blocking performance. A high turn-on voltage of 1.36 V is obtained for the NiOx/Nb2O5 p-n junction. An open-circuit voltage of 1.16 V is achieved using a hybrid organic-inorganic perovskite with a band gap of 1.6 eV. The large photovoltage, enabled by the excellent charge extraction and blocking properties of the inorganic selective contact layers, leads to the highest PCE of over 19.0% for this class of device.

CsPbCl3-Driven Low-Trap-Density Perovskite Grain Growth for >20% Solar Cell Efficiency.

Charge recombination in grain boundaries is a significant loss mechanism for perovskite (PVK) solar cells. Here, a new strategy is demonstrated to effectively passivate trap states at the grain boundaries. By introducing a thin layer of CsPbCl3 coating before the PVK deposition, a passivating layer of PbI2 is formed at the grain boundaries. It is found that at elevated temperature, Cl- ions in the CsPbCl3 may migrate into the PVK via grain boundaries, reacting with MA+ to form volatile MACl and leaving a surface layer of PbI2 at the grain boundary. Further study confirms that there is indeed a small amount of PbI2 distributed throughout the grain boundaries, resulting in increased photoluminescence intensity, increased carrier lifetime, and decreased trap state density. It is also found that the process passivates only grain surfaces, with no observable effect on the morphology of the PVK thin film. Upon optimization, the obtained PVK-film-based solar cell delivers a high efficiency of 20.09% with reduced hysteresis and excellent stability.

Magnetic Field-Assisted Perovskite Film Preparation for Enhanced Performance of Solar Cells.

Perovskite solar cells (PSCs) are promising low-cost photovoltaic technologies with high power conversion efficiency (PCE). The crystalline quality of perovskite materials is crucial to the photovoltaic performance of the PSCs. Herein, a simple approach is introduced to prepare high-quality CH3NH3PbI3 perovskite films with larger crystalline grains and longer carriers lifetime by using magnetic field to control the nucleation and crystal growth. The fabricated planar CH3NH3PbI3 solar cells have an average PCE of 17.84% and the highest PCE of 18.56% using an optimized magnetic field at 80 mT. In contrast, the PSCs fabricated without the magnetic field give an average PCE of 15.52% and the highest PCE of 16.72%. The magnetic field action produces an ordered arrangement of the perovskite ions, improving the crystallinity of the perovskite films and resulting in a higher PCE.

Expression and correlation of sex hormone-binding globulin and insulin signal transduction and glucose transporter proteins in gestational diabetes mellitus placental tissue.

OBJECTIVE: The aim of the present study was to investigate the probable pathogenesis of gestational diabetes mellitus (GDM) by analyzing the correlation between sex hormone-binding globulin (SHBG) secreted by the placenta during pregnancy and insulin signaling components and glucose transporter proteins (GLUTs) in the placental tissue. DESIGN AND METHODS: Placental tissue was collected from full-term and non-obese [body mass index <25kg/m(2)] pregnant women; 10 diagnosed with GDM and 10 with normal pregnancy. We used real-time polymerase chain reaction (PCR), immunohistochemistry and western blotting to detect expression of protein and mRNA of SHBG and insulin signaling components and GLUTs in placental tissue. RESULTS: In the placental tissue of non-obese women, there was a decrease in expression of SHBG protein and mRNA, with a concurrent decrease in expression of GLUT-4 protein and mRNA in women with GDM compared with normal controls. There was a decrease in GLUT-3 and insulin receptor substrate (IRS)-1 protein expression and lower IRS-2 mRNA expression was also observed in GDM placental tissue. Linear correlation analyses showed a positive correlation between SHBG and IRS-2 mRNA (P=0.038, R(2)=0.2178, y=0.249x+1.4208); positive correlation between SHBG and phosphatidylinositol 3-kinase (PI3K) p85α mRNA (P=0.035, R(2)=0.224, y=0.3506x+0.7433); positive correlation between SHBG and GLUT-4 mRNA (P=0.000, R(2)=0.5174, y=1.3822+1.7811x); positive correlation between IRS-2 and GLUT-4 mRNA (P=0.002, R(2)=0.4064, y=-0.8272+2.9592x); negative correlation between IRS-1 and PI3K p85α mRNA (P=0.005, R(2)=0.366, y=2.4492-0.1929x); negative correlation between IRS-1 and GLUT-3 mRNA (P=0.027, R(2)=0.243, y=0.9254-0.0714x); and positive correlation between IRS-2 and GLUT-1 mRNA (P=0.004, R(2)=0.3794, y=0.0225+0.6298x). CONCLUSION: The results confirm that defective receptors for insulin signal transduction and GLUT proteins are present in GDM placental tissue. Decreasing expression of SHBG may participate in regulation of insulin signaling, leading to a concomitant decrease in expression of relevant insulin signaling components in placental tissue, implying insulin resistance and eventual development of GDM.