Galectin-3 impairs calcium transients and ß-cell function.

In diabetes, macrophages and inflammation are increased in the islets, along with ß-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in ß-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. ß-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and db/db mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic ß-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.

Reduced graphene oxide-encaged submicron-silicon anode interfacially stabilized by Al2O3 nanoparticles for efficient lithium-ion batteries.

Silicon-carbon composites have been recognized as some of the most promising anode candidates for advancing new-generation lithium-ion batteries (LIBs). The development of high-efficiency silicon/graphene anodes through a simple and cost-effective preparation route is significant. Herein, by using micron silicon as raw material, we designed a mesoporous composite of silicon/alumina/reduced graphene oxide (Si/Al2O3/RGO) via a two-step ball milling combined annealing process. Commercial Al2O3 nanoparticles are introduced as an interlayer due to the toughening effect, while RGO nanosheets serve as a conductive and elastic coating to protect active submicron silicon particles during lithium alloying/dealloying reactions. Owing to the rational porous structure and dual protection strategy, the core/shell structured Si/Al2O3/RGO composite is efficient for Li+ storage and demonstrates improved electrical conductivity, accelerated charge transfer and electrolyte diffusion, and especially high structural stability upon charge/discharge cycling. As a consequence, Si/Al2O3/RGO yields a high discharge capacity of 852 mA h g-1 under a current density of 500 mA g-1 even after 200 cycles, exhibiting a high capacity retention of ∼85%. Besides, Si/Al2O3/RGO achieves excellent cycling reversibility and superb high-rate capability with a stable specific capacity of 405 mA h g-1 at 3000 mA g-1. Results demonstrate that the Al2O3 interlayer is synergistic with the indispensable RGO nanosheet shells, affording more buffer space for silicon cores to alleviate the mechanical expansion and thus stabilizing active silicon species during charge/discharge cycles. This work provides an alternative low-cost approach to achieving high-capacity silicon/carbon composites for high-performance LIBs.

Understanding and Weakening Photon Recycling in Solar Cells to Approach the Radiative Limit.

Photon recycling plays an important role in the light outcoupling of state-of-the-art solar cells and is considered a necessary condition to achieve the radiative limit of open-circuit voltage (VOC) and efficiency. However, due to the impact of photon recycling on bulk and surface radiation of solar cells being overlooked, experimental demonstrations on the accuracy of existing photon recycling models are scarce and some contrary theoretical results also emerge. Here, the relationship between photon recycling and radiation processes, as well as the corresponding VOC losses of solar cells based on the principle of detailed balance is clarified. It is shown that weakening photon recycling is more effective to boost the device performance than enhancing it, promoting the theoretical efficiencies of solar cells, such as perovskite, Si, and GaAs, to 98.5%, 94.9%, and almost 100% of their radiative limit, respectively. Moreover, weakening photon recycling also helps to maintain higher efficiency when the internal radiative efficiency decreases, which benefits higher device stability. This work provides an in-depth understanding of the role of photon recycling in solar cells and helps to push efficiency to a new limit.

Trimethylamine N-oxide impairs ß-cell function and glucose tolerance.

ß-Cell dysfunction and ß-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to that found in diabetes could directly decrease glucose-stimulated insulin secretion (GSIS) in MIN6 cells and primary islets from mice or humans. Elevation of TMAO levels impairs GSIS, ß-cell proportion, and glucose tolerance in male C57BL/6 J mice. TMAO inhibits calcium transients through NLRP3 inflammasome-related cytokines and induced Serca2 loss, and a Serca2 agonist reversed the effect of TMAO on ß-cell function in vitro and in vivo. Additionally, long-term TMAO exposure promotes ß-cell ER stress, dedifferentiation, and apoptosis and inhibits ß-cell transcriptional identity. Inhibition of TMAO production improves ß-cell GSIS, ß-cell proportion, and glucose tolerance in both male db/db and choline diet-fed mice. These observations identify a role for TMAO in ß-cell dysfunction and maintenance, and inhibition of TMAO could be an approach for the treatment of T2D.

Isolating the Oxygen Adsorption Defects on Sputtered Tin Oxide for Efficient Perovskite Solar Cells.

Tin oxide (SnO2) is the most commonly used electron transport material for perovskite solar cells (PSCs). Various techniques have been applied to deposit tin dioxide, including spin-coating, chemical bath deposition, and magnetron sputtering. Among them, magnetron sputtering is one of the most mature industrial deposition techniques. However, PSCs based on magnetron-sputtered tin oxide (sp-SnO2) have a lower open-circuit voltage (Voc) and power conversion efficiency (PCE) than those prepared by the mainstream solution method. This is mainly due to the oxygen-related defects at the sp-SnO2/perovskite interface, and traditional passivation strategies usually have little effect on them. Herein, we successfully isolate the oxygen adsorption (Oads) defects located on the surface of sp-SnO2 from the perovskite layer using a PCBM double-electron transport layer. This isolation strategy effectively suppresses the Shockley-Read-Hall recombination at the sp-SnO2/perovskite interface, which results in an increase in the Voc from 0.93 to 1.15 V and an increase in PCE from 16.66 to 21.65%. To our knowledge, this is the highest PCE achieved using a magnetron-sputtered charge transport layer to date. The unencapsulated devices maintain 92% of their initial PCE after storage in air with a relative humidity of 30-50% after 750 h. We further use the solar cell capacitance simulator (1D-SCAPS) to confirm the effectiveness of the isolation strategy. This work highlights the application prospect of magnetron sputtering in the field of perovskite solar cells and provides a simple yet effective way to tackle the interfacial defect issue.

Hepatocyte leukotriene B4 receptor 1 promotes NAFLD development in obesity.

BACKGROUND AND AIMS: NAFLD is the most prevalent chronic liver disease worldwide and has emerged as a serious public health issue with no approved treatment. The development of NAFLD is strongly associated with hepatic lipid content, and patients with NAFLD have significantly higher rates of hepatic de novo lipogenesis (DNL) than lean individuals. Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is dramatically increased in obesity and plays important role in proinflammatory cytokine production and insulin resistance. But the role of liver LTB4/LTB4 receptor 1 (Ltb4r1) in lipid metabolism is unclear. APPROACH AND RESULTS: Hepatocyte-specific knockout (HKO) of Ltb4r1 improved hepatic steatosis and systemic insulin resistance in both diet-induced and genetically induced obese mice. The mRNA level of key enzymes involved in DNL and fatty acid esterification decreased in Ltb4r1 HKO obese mice. LTB4/Ltb4r1 directly promoted lipogenesis in HepG2 cells and primary hepatocytes. Mechanically, LTB4/Ltb4r1 promoted lipogenesis by activating the cAMP-protein kinase A (PKA)-inositol-requiring enzyme 1α (IRE1α)-spliced X-box-binding protein 1 (XBP1s) axis in hepatocytes, which in turn promoted the expression of lipogenesis genes regulated by XBP1s. In addition, Ltb4r1 suppression through the Ltb4r1 inhibitor or lentivirus-short hairpin RNA delivery alleviated the fatty liver phenotype in obese mice. CONCLUSIONS: LTB4/Ltb4r1 promotes hepatocyte lipogenesis directly by activating PKA-IRE1α-XBP1s to promote lipogenic gene expression. Inhibition of hepatocyte Ltb4r1 improved hepatic steatosis and insulin resistance. Ltb4r1 is a potential therapeutic target for NAFLD.

Flexible and Conductive Polymer Threads for Efficient Fiber-Shaped Supercapacitors via Vapor Copolymerization.

Flexible fiber electrodes are critical for high-performance fiber and wearable electronics. In this work, we presented a highly conductive all-polymer fiber electrode by vapor copolymerization of 2,5-dibromo-3,4-vinyldioxythiophene (DBEDOT) and 2,5-diiodo-3,4-vinyldioxythiophene (DIEDOT) monomers on commonly used polyester threads (PETs) at a temperature as low as 80 °C. The poly(3,4-ethylenedioxythiophene) (PEDOT)-coated PET threads maintain excellent flexibility and show conductivity of 7.93 S cm-1, nearly four times higher than that reported previously via homopolymerization of DBEDOT monomer. A MnO2 active layer was embedded into the PEDOT double layers, and the flexible fiber composite electrode showed a high linear specific capacitance of 157 mF cm-1 and improved stability, retaining 86.5% capacitance after 5000 cycles. Fiber-shaped solid-state supercapacitors (FSSCs) based on the composite electrodes were assembled, and they displayed superior electrochemical performance. This work provides a new approach to realize high-performance and stable wearable electronics.

Insulin induces insulin receptor degradation in the liver through EphB4.

Insulin signaling is essential for glucose metabolism, and insulin decreases insulin receptor (InsR) levels in a dose-dependent and time-dependent manner. However, the regulatory mechanisms of InsR reduction upon insulin stimulation remain poorly understood. Here, we show that Eph receptor B4 (EphB4), a tyrosine kinase receptor that modulates cell adhesion and migration, can bind directly to InsR, and this interaction is markedly enhanced by insulin. Due to the adaptor protein 2 (Ap2) complex binding motif in EphB4, the interaction of EphB4 and InsR facilitates clathrin-mediated InsR endocytosis and degradation in lysosomes. Hepatic overexpression of EphB4 decreases InsR and increases hepatic and systemic insulin resistance in chow-fed mice, whereas genetic or pharmacological inhibition of EphB4 improve insulin resistance and glucose intolerance in obese mice. These observations elucidate a role for EphB4 in insulin signaling, suggesting that EphB4 might represent a therapeutic target for the treatment of insulin resistance and type 2 diabetes.

Doping Mechanism of Perovskite Films with PbCl2 Prepared by Magnetron Sputtering for Enhanced Efficiency of Solar Cells.

The last decade has witnessed a rapid growth of perovskite solar cells extended from mesoporous to planar architecture as well as from solution processing to solvent-free fabrication. The preparation of perovskite films by solvent-free method still presents significant challenges, such as the difficulty of film preparation by multiple evaporation sources in vapor deposition and the immaturity of the sputtered method. Here, we present a planar perovskite solar cell fabricated by solvent-free magnetron sputtering without the assistance of the mesoporous TiO2 layer, and lead chloride (PbCl2) was mechanically milled into the target of methylammonium lead halides (MAPbI3) to improve the quality of perovskite film by regulating the crystallization process with the Cl element. Furthermore, the internal reason for the effect of different PbCl2 doping contents on the trap density of perovskite films was also investigated in detail. These lead to an improved power conversion efficiency of planar heterojunction perovskite solar cells up to 17.10%, which is the highest efficiency recorded for the sputtered perovskite solar cells so far. The stability of resulting solar cells has also been significantly improved by exploring the doping mechanism of perovskite films with PbCl2 in detail, showing great research and application prospect.

Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects.

Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs of FGFR1c in diabetic mice we identified the paracrine FGF4 as a potent anti-hyperglycemic FGF. Importantly, we found that like FGF1, the paracrine FGF4 is also more efficacious than endocrine FGF21 in lowering blood glucose. We show that paracrine FGF4 and FGF1 exert their superior glycemic control by targeting skeletal muscle, which expresses copious FGFR1c but lacks ß-klotho (KLB), an obligatory FGF21 co-receptor. Mechanistically, both FGF4 and FGF1 upregulate GLUT4 cell surface abundance in skeletal muscle in an AMPKα-dependent but insulin-independent manner. Chronic treatment with rFGF4 improves insulin resistance and suppresses adipose macrophage infiltration and inflammation. Notably, unlike FGF1 (a pan-FGFR ligand), FGF4, which has more restricted FGFR1c binding specificity, has no apparent effect on food intake. The potent anti-hyperglycemic and anti-inflammatory properties of FGF4 testify to its promising potential for use in the treatment of T2D and related metabolic disorders.

Van der Waals heterostructure polaritons with moiré-induced nonlinearity.

Controlling matter-light interactions with cavities is of fundamental importance in modern science and technology1. This is exemplified in the strong-coupling regime, where matter-light hybrid modes form, with properties that are controllable by optical-wavelength photons2,3. By contrast, matter excitations on the nanometre scale are harder to access. In two-dimensional van der Waals heterostructures, a tunable moiré lattice potential for electronic excitations may form4, enabling the generation of correlated electron gases in the lattice potentials5-9. Excitons confined in moiré lattices have also been reported10,11, but no cooperative effects have been observed and interactions with light have remained perturbative12-15. Here, by integrating MoSe2-WS2 heterobilayers in a microcavity, we establish cooperative coupling between moiré-lattice excitons and microcavity photons up to the temperature of liquid nitrogen, thereby integrating versatile control of both matter and light into one platform. The density dependence of the moiré polaritons reveals strong nonlinearity due to exciton blockade, suppressed exciton energy shift and suppressed excitation-induced dephasing, all of which are consistent with the quantum confined nature of the moiré excitons. Such a moiré polariton system combines strong nonlinearity and microscopic-scale tuning of matter excitations using cavity engineering and long-range light coherence, providing a platform with which to study collective phenomena from tunable arrays of quantum emitters.

The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving ß cell function in pre-diabetic KKAy mice.

Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved ß cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The ß cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting ß cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in ß cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of ß cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting ß cell function and preventing the onset of pre-diabetes to T2DM.

Nanoscale Mapping of Morphology of Organic Thin Films.

We determine precise nanoscale information about the morphologies of several organic thin film structures using Fourier plane imaging microscopy (FIM). We used FIM microscopy to detect the orientation of molecular transition dipole moments from an extremely low density of luminescent dye molecules, which we call "morphology sensors". The orientation of the sensor molecules is driven by the local film structure and thus can be used to determine details of the host morphology without influencing it. We use symmetric planar phosphorescent dye molecules as the sensors that are deposited into the bulk of organic film hosts during the growth. We demonstrate morphological mapping with a depth resolution to a few Ångstroms that is limited by the ability to determine thickness during deposition, along with an in-plane resolution limited by optical diffraction. Furthermore, we monitor morphological changes arising from thermal annealing of metastable organic films that are commonly employed in photonic devices.

Twist-angle dependence of moiré excitons in WS2/MoSe2 heterobilayers.

Moiré lattices formed in twisted van der Waals bilayers provide a unique, tunable platform to realize coupled electron or exciton lattices unavailable before. While twist angle between the bilayer has been shown to be a critical parameter in engineering the moiré potential and enabling novel phenomena in electronic moiré systems, a systematic experimental study as a function of twist angle is still missing. Here we show that not only are moiré excitons robust in bilayers of even large twist angles, but also properties of the moiré excitons are dependant on, and controllable by, the moiré reciprocal lattice period via twist-angle tuning. From the twist-angle dependence, we furthermore obtain the effective mass of the interlayer excitons and the electron inter-layer tunneling strength, which are difficult to measure experimentally otherwise. These findings pave the way for understanding and engineering rich moiré-lattice induced phenomena in angle-twisted semiconductor van der Waals heterostructures.

Fast Organic Vapor Phase Deposition of Thin Films in Light-Emitting Diodes.

Fast deposition of thin films is essential for achieving low-cost, high-throughput phosphorescent organic light-emitting diode (PHOLED) production. In this work, we demonstrate rapid and uniform growth of semiconductor thin films by organic vapor phase deposition (OVPD). A green PHOLED comprising an emission layer (EML) grown at 50 Å/s with bis[2-(2-pyridinyl-N)phenyl-C](acetylacetonato)iridium(III) (Ir(ppy)2(acac)) doped into 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP) exhibits a maximum external quantum efficiency of 20 ± 1%. The morphology, charge transport properties, and radiative efficiency under optical and electrical excitation of the PHOLED EML are investigated as functions of the deposition rate via both experimental and theoretical approaches. The EML shows no evidence for gas phase nucleation of the organic molecules at deposition rates as high as 50 Å/s. However, the roll-off in quantum efficiency at high current progressively increases with deposition rate due to enhanced triplet-polaron annihilation. The roll-off results from accumulation of stress within the PHOLED EML that generates a high density of defect states. The defects, in turn, act as recombination sites for triplets and hole polarons, leading to enhanced triplet-polaron annihilation at high current. We introduce a void nucleation model to describe the film morphology evolution that is observed using electron microscopy.

Ultralong-Range Energy Transport in a Disordered Organic Semiconductor at Room Temperature Via Coherent Exciton-Polariton Propagation.

Amorphous molecular solids are inherently disordered, exhibiting strong exciton localization. Optical microcavities containing such disordered excitonic materials have been theoretically shown to support both propagating and localized exciton-polariton modes. Here, the ultrastrong coupling of a Bloch surface wave photon and molecular excitons in a disordered organic thin film at room temperature is demonstrated, where the major fraction of the polaritons are propagating states. The delocalized exciton-polariton has a group velocity as high as 3 × 107 m s-1 and a lifetime of 500 fs, leading to propagation distances of over 100 µm from the excitation source. The polariton intensity shows a halo-like pattern that is due to self-interference of the polariton mode, from which a coherence length of 20 µm is derived and is correlated with phase breaking by polariton scattering. The demonstration of ultralong-range exciton-polariton transport at room temperature promises new photonic and optoelectronic applications such as efficient energy transfer in disordered condensed matter systems.

Hepatic DNAJB9 Drives Anabolic Biasing to Reduce Steatosis and Obesity.

Nutrients stimulate the anabolic synthesis of proteins and lipids, but selective insulin resistance in obesity biases the anabolic program toward lipogenesis. Here, we report the identification of a DNAJB9-driven program that favors protein synthesis and energy production over lipid accumulation. We show there are two pools of DNAJB9 cochaperone. DNAJB9 in the ER lumen promotes the degradation of the lipogenic transcription factor SREBP1c through ERAD, whereas its counterpart on the ER membrane promotes the assembly of mTORC2 in the cytosol and stimulates the synthesis of proteins and ATP. The expression of Dnajb9 is induced by nutrients and downregulated in the obese mouse liver. Restoration of hepatic DNAJB9 expression effectively improves insulin sensitivity, restores protein synthesis, and suppresses food intake, accompanied by reduced hepatic steatosis and adiposity in multiple mouse models of obesity. Therefore, targeting the anabolic balance may provide a unique opportunity to tackle obesity and diabetes.

Enhanced Light Utilization in Semitransparent Organic Photovoltaics Using an Optical Outcoupling Architecture.

Building-integrated photovoltaics employing transparent photovoltaic cells on window panes provide an opportunity to convert solar energy to electricity rather than generating waste heat. Semitransparent organic photovoltaic cells (ST-OPVs) that utilize a nonfullerene acceptor-based near-infrared (NIR) absorbing ternary cell combined with a thin, semitransparent, high conductivity Cu-Ag alloy electrode are demonstrated. A combination of optical outcoupling and antireflection coatings leads to enhanced visible transmission, while reflecting the NIR back into the cell where it is absorbed. This combination of coatings results in doubling of the light utilization efficiency (LUE), which is equal to the product of the power conversion efficiency (PCE) and the average photopic transparency, compared with a conventional semitransparent cell lacking these coatings. A maximum LUE = 3.56 ± 0.11% is achieved for an ST-OPV with a PCE = 8.0 ± 0.2% at 1 sun, reference AM1.5G spectrum. Moreover, neutral colored ST-OPVs are also demonstrated, with LUE = 2.56 ± 0.2%, along with Commission Internationale d'Eclairage chromaticity coordinates of CIE = (0.337, 0.349) and a color rendering index of CRI = 87.

Reducing Architecture Limitations for Efficient Blue Perovskite Light-Emitting Diodes.

Light-emitting diodes utilizing perovskite nanocrystals have generated strong interest in the past several years, with green and red devices showing high efficiencies. Blue devices, however, have lagged significantly behind. Here, it is shown that the device architecture plays a key role in this lag and that NiOx , a transport layer in one of the highest efficiency devices to date, causes a significant reduction in perovskite luminescence lifetime. An alternate transport layer structure which maintains robust nanocrystal emission is proposed. Devices with this architecture show external quantum efficiencies of 0.50% at 469 nm, seven times higher than state-of-the-art devices at that wavelength. Finally, it is demonstrated that this architecture enables efficient devices across the entire blue-green portion of the spectrum. The improvements demonstrated here open the door to efficient blue perovskite light-emitting diodes.

Inflammation and insulin resistance: New targets encourage new thinking: Galectin-3 and LTB4 are pro-inflammatory molecules that can be targeted to restore insulin sensitivity.

Galectin-3 and LTB4 are pro-inflammatory molecules recently shown to directly cause insulin resistance in mouse and human cells. They are highly expressed in the obese state, and can be targeted both genetically and pharmacologically to improve insulin sensitivity in vivo. This expands on previous research showing that targeting inflammatory cytokines can be insulin sensitizing in animal models. However, translating these potential therapies into the human setting remains challenging. Here we review this latest research, and discuss how balancing their pleiotropic functions, the action of the microbiome, and the ability to identify relevant patient populations are vital considerations for successful anti-inflammatory insulin sensitizing therapy.