Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration.

BACKGROUND: The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown. METHODS AND RESULTS: This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients. CONCLUSIONS: Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.

Spatiotemporal Investigation of Intercellular Heterogeneity via Multiple Photocaged Probes.

Intercellular heterogeneity occurs widely under both normal physiological environments and abnormal disease-causing conditions. Several attempts to couple spatiotemporal information to cell states in a microenvironment were performed to decipher the cause and effect of heterogeneity. Furthermore, spatiotemporal manipulation can be achieved with the use of photocaged/photoactivatable molecules. Here, we provide a platform to spatiotemporally analyze differential protein expression in neighboring cells by multiple photocaged probes coupled with homemade photomasks. We successfully established intercellular heterogeneity (photoactivable ROS trigger) and mapped the targets (directly ROS-affected cells) and bystanders (surrounding cells), which were further characterized by total proteomic and cysteinomic analysis. Different protein profiles were shown between bystanders and target cells in both total proteome and cysteinome. Our strategy should expand the toolkit of spatiotemporal mapping for elucidating intercellular heterogeneity.

Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex.

OBJECTIVE: Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear. Approach and Results: Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis. Nε-carboxymethyllysine (CML) and inflammatory cytokines levels in human sera and in several diabetic murine models were detected by ELISA, whereas liquid chromatography-tandem mass spectrometry analysis was used for whole eye tissues. The CML and p-Tpl2 expressions on the human retinal pigment epithelium (RPE) cells were determined by immunofluorescence. Intravitreal injection of pharmacological inhibitor or NA (neutralizing antibody) was used in a diabetic rat model. Retinal leukostasis, optical coherence tomography, and H&E staining were used to observe pathological features. Sera of diabetic retinopathy patients had significantly increased CML levels that positively correlated with diabetic retinopathy severity and foveal thickness. CML and p-Tpl2 expressions also significantly increased in the RPE of both T1DM and T2DM diabetes animal models. Mechanistic studies on RPE revealed that CML-induced Tpl2 activation and NADPH oxidase, and inflammasome complex activation were all effectively attenuated by Tpl2 inhibition. Tpl2 inhibition by NA also effectively reduced inflammatory/angiogenic factors, retinal leukostasis in streptozotocin-induced diabetic rats, and RPE secretion of inflammatory cytokines. The attenuated release of angiogenic factors led to inhibited vascular abnormalities in the diabetic animal model. CONCLUSIONS: The inhibition of Tpl2 can block the inflammasome signaling pathway in RPE and has potential clinical and therapeutic implications in diabetes-associated retinal microvascular dysfunction.

Improved diffusion and storage of lithium ions via recrystallization induced conducting pathways in a Li:Ta2O5-based electrolyte for all-solid-state electrochromic devices with enhanced performance.

In this study, we have investigated the improvements in the performance of an all-solid-state complementary electrochromic device (ECD) by using the proposed high pressure treatment (HPT). The Li:Ta2O5electrolyte layer was recrystallized by the HPT utilizing pressurized CO2gas (∼200 atm) and at low temperature (<60 °C), which enhanced the coloration performance of the WO3/Li:Ta2O5/NiO complementary ECD by ∼20%. The reliability and durability of the ECD were confirmed by long term transmittance retention measurements, which indicated an improvement in the coloration performance by ∼14% upon the release of the bias voltages. The ability of the devices that were fabricated with and without the HPT process to withstand high temperature environments was also verified. In addition, photoluminescence (PL) and transmittance measurements were carried out to examine the effects of the bonding between WO3and NiO. To determine the differences in lithium-ion (Li+) injection, electrical measurements were performed by utilizing varying pulse rising speeds to confirm device characteristics. The materials were characterized in terms of their composition and structure using high-resolution transmission electron microscopy along with energy-dispersive x-ray spectroscopy. Finally, a mechanistic model has been proposed to explain the improved EC characteristics based on the amorphous to crystalline transition accompanying the HPT process.

Adaptive Synaptic Memory via Lithium Ion Modulation in RRAM Devices.

Biologically plausible computing systems require fine-grain tuning of analog synaptic characteristics. In this study, lithium-doped silicate resistive random access memory with a titanium nitride (TiN) electrode mimicking biological synapses is demonstrated. Biological plausibility of this RRAM device is thought to occur due to the low ionization energy of lithium ions, which enables controllable forming and filamentary retraction spontaneously or under an applied voltage. The TiN electrode can effectively store lithium ions, a principle widely adopted from battery construction, and allows state-dependent decay to be reliably achieved. As a result, this device offers multi-bit functionality and synaptic plasticity for simulating various strengths in neuronal connections. Both short-term memory and long-term memory are emulated across dynamical timescales. Spike-timing-dependent plasticity and paired-pulse facilitation are also demonstrated. These mechanisms are capable of self-pruning to generate efficient neural networks. Time-dependent resistance decay is observed for different conductance values, which mimics both biological and artificial memory pruning and conforms to the trend of the biological brain that prunes weak synaptic connections. By faithfully emulating learning rules that exist in human's higher cortical areas from STDP to synaptic pruning, the device has the capacity to drive forward the development of highly efficient neuromorphic computing systems.

Chemical Constituents from the Stems of Tinospora sinensis and Their Bioactivity.

Fifty-seven compounds were purified from the stems of Tinospora sinensis, including three new compounds characterized as a lignan (1), a pyrrole alkaloid (11), and a benzenoid (17), respectively. Their structures were elucidated and established by various spectroscopic and spectrometric analytical methods. Among the isolates, fifteen compounds were examined for their anti-inflammatory potential in vitro. The results showed that several compounds displayed moderate inhibition of N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release.

Insulinoma in a young female patient with systemic lupus erythematosus: a case report.

OBJECTIVE: Fasting hypoglycemia may occur in subjects with systemic lupus erythematosus (SLE) when accompanied with insulin-binding antibodies or insulin-receptor antibodies. However, insulinoma has not been reported in SLE subjects with hypoglycemia. METHODS: We present a case report and review the relevant literature. RESULTS: A 26-year-old female with underlying SLE experienced several episodes of neuropsychiatric symptoms in a fasting state. The steroid dosage was titrated up, but in vain. Timely imaging studies showed a pancreatic tumor, and insulinoma was proven by pathology. Hypoglycemia did not recur after surgery. CONCLUSION: Physicians should distinguish insulinoma from autoimmunity-mediated hypoglycemia in SLE patients with fasting hypoglycemia.

Suppressed quantum-confined Stark effect in InGaN-based LEDs with nano-sized patterned sapphire substrates.

This paper demonstrates that quantum-confined Stark effect (QCSE) within the multiple quantum wells (MQWs) can be suppressed by the growths of InGaN-based light-emitting diodes (LEDs) on the nano-sized patterned c-plane sapphire substrates (PCSSs) with reducing the space. The efficiency droop is also determined by QCSE. As verified by the experimentally measured data and the ray-tracing simulation results, the suppressed efficiency droop for the InGaN-based LED having the nano-sized PCSS with a smaller space of 200 nm can be acquired due to the weaker function of the QCSE within the MQWs as a result of the smaller polarization fields coming from the lower compressive strain in the corresponding epitaxial layers.

General Strategies for Preparing Hybrid Polymer/Quantum Dot Nanocomposites for Color Conversion.

Quantum dots (QDs), with their exceptional optical properties, have emerged as promising candidates to replace traditional phosphors in lighting and display technologies. This study delves into the integration strategies of QDs within glass and polymer matrices to engineer advanced quantum dot color converters (QDCCs) at the industrial scale for practical applications. To achieve enhancements in the photostability and thermal stability of QDCCs, we explore two distinct approaches: the dispersion of QDs in a hydrophilic glass matrix via a sol-gel process and the incorporation of QDs into a non-polar acrylate monomer to formulate QD/polymer nanocomposites. This research further investigates the optical behaviors of these composites, focusing on their light-scattering and propagation mechanisms, which are critical for optimizing light extraction efficiency in QDCCs. Additional optical film and light-scattering particles can improve color conversion efficiency by ~140%. These advancements present a significant step forward in the development of high-performance, energy-efficient, QD-based lighting and display systems.

Enhanced Photostability of Core/Shell Quantum Dots under Intense Blue Light Irradiation through Positive Photoaging Mechanism.

Photostability of semiconductor core/shell quantum dots (QDs) has historically been perceived as intricate and unpredictable. Notably, the long-term luminescence stability of QDs under light exposure does not seem to consistently correspond with their characteristics in the absence of light. In this study, we propose a positive photoaging mechanism of QDs, integrating both ligand/shell-induced photobrightening and surface photo-oxidation, to deal with the photostability nuances. When QDs are subjected to higher energy light, their photobrightening and photodarkening conjointly determine the photostability. Enhanced photostability may not be simply attributed to a thicker shell or the presence of ligands. When adjusted with an optimal shell thickness and supplemented with negatively charged ligands, QDs exhibit enhanced photostability in both solvents and polymers.

Investigating Selectorless Property within Niobium Devices for Storage Applications.

Resistive random-access memory (RRAM) crossbar arrays have shown significant promise as drivers of neuromorphic computing, in-memory computing, and high-density storage-class memory applications. However, leakage current through parasitic sneak paths is one of the dominant obstacles for large-scale commercial deployment of RRAM arrays. To overcome this issue without compromising on the structural simplicity, the use of inherent selectors native to switching is one of the most promising ways to reduce sneak path currents without sacrificing density associated with the simple two-electrode structure. In this study, niobium oxide (NbOx) was chosen as the resistive switching layer since it co-exhibits non-volatile memory and metal-insulator-transition selector behavior. Experimental results demonstrate abnormal phenomena in the reset process: a rapid decrease in current, followed by an increase when reset from the on state. The current conduction mechanism was examined through statistical analysis, and a conduction filament physical model was developed to explain the abnormal phenomenon. Under optimized operation conditions, non-linearity of ∼500 and fast switching speeds of 30 ns set and 50 ns reset were obtained. The switching behaviors with the intrinsic selector property make the NbOx device an attractive candidate for future memory and in-memory computing applications.

Friction and Wear Performance of Staple Carbon Fabric-Reinforced Composites: Effects of Surface Topography.

Here, staple carbon fiber fabric-reinforced polycarbonate (PC)- and epoxy (EP)-based composites with different impregnating resin levels were fabricated using a modified film stacking process. The effects of surface topographies and resin types on the tribological properties of stable carbon fabric composites (sCFC) were investigated. Friction and wear tests on the carbon composites were conducted under unlubricated sliding using a disk-on-disk wear test machine. Experimental results showed that the coefficient of friction (COF) of the sCFC was dominated by matrix type, followed by peak material portion (Smr1) values, and finalized with core height (Sk) values. The COF of composites decreased by increasing the sliding speed and applied pressure. This also relied on surface topography and temperature generated at the worn surface. However, the specific wear rate was strongly affected by resin impregnation. Partially-impregnated composites showed lower specific wear rate, whereas fully-impregnated composites showed a higher wear rate. This substantially increased by increasing the sliding speed and applied pressure. Scanning electron microscopy observations of the worn surfaces revealed that the primary wear mechanisms were abrasion, adhesion, and fatigue for PC-based composites. For EP-based composites, this was primarily abrasion and fatigue. Results proved that partially-impregnated composites exhibited better tribological properties under severe conditions.

Approximate Mortality Risks between Hyperuricemia and Diabetes in the United States.

Aim: This study aimed to compare mortality risks across uric acid (UA) levels between non-diabetes adults and participants with diabetes and to investigate the association between hyperuricemia and mortality risks in low-risk adults. Methods: We analyzed data from adults aged >18 years without coronary heart disease and chronic kidney disease (n = 29,226) from the National Health and Nutrition Examination Survey (1999-2010) and the associated mortality data (up to December 2011). We used the Cox proportional hazards models to examine the risk of all-cause and cause-specific (cardiovascular disease (CVD) and cancer) mortality at different UA levels between adults with and without diabetes. Results: Over a median follow-up of 6.6 years, 2069 participants died (495 from CVD and 520 from cancers). In non-diabetes adults at UA ≥ 5 mg/dL, all-cause and CVD mortality risks increased across higher UA levels (p-for-trend = 0.037 and 0.058, respectively). The lowest all-cause mortality risk in participants with diabetes was at the UA level of 5-7 mg/dL. We set the non-diabetes participants with UA levels of <7 mg/dL as a reference group. Without considering the effect of glycemic control, the all-cause mortality risk in non-diabetes participants with UA levels of ≥7 mg/dL was equivalent to risk among diabetes adults with UA levels of <7 mg/dL (hazard ratio = 1.44 vs. 1.57, p = 0.49). A similar result was shown in CVD mortality risk (hazard ratio = 1.80 vs. 2.06, p = 0.56). Conclusion: Hyperuricemia may be an indicator to manage multifaceted cardiovascular risk factors in low-risk adults without diabetes, but further studies and replication are warranted.

Reducing Interface Traps with High Density Hydrogen Treatment to Increase Passivated Emitter Rear Contact Cell Efficiency.

In this work, a high-density hydrogen (HDH) treatment is proposed to reduce interface traps and enhance the efficiency of the passivated emitter rear contact (PERC) device. The hydrogen gas is compressed at pressure (~ 70 atm) and relatively low temperature (~ 200 °C) to reduce interface traps without changing any other part of the device's original fabrication process. Fourier-transform infrared spectroscopy (FTIR) confirmed the enhancement of Si-H bonding and secondary-ion mass spectrometry (SIMS) confirmed the SiN/Si interface traps after the HDH treatment. In addition, electrical measurements of conductance-voltage are measured and extracted to verify the interface trap density (Dit). Moreover, short circuit current density (Jsc), series resistance (Rs), and fill factor (F.F.) are analyzed with a simulated light source of 1 kW M-2 global AM1.5 spectrum to confirm the increase in cell efficiency. External quantum efficiency (EQE) is also measured to confirm the enhancement in conversion efficiency between different wavelengths. Finally, a model is proposed to explain the experimental result before and after the treatment.

Investigation of the Capacitance-Voltage Electrical Characteristics of Thin-Film Transistors Caused by Hydrogen Diffusion under Negative Bias Stress in a Moist Environment.

In this study, the impact of moisture on the electrical characteristics of an amorphous In-Ga-Zn-O thin-film transistor (a-IGZO TFT) was investigated. In commercial applications of such TFTs, high stability and quality performance in humid environments are essential. During TFT operation under ambient moisture, the electrolysis of water molecules occurs via the tip electric field effect. Hydrogen diffuses from the etch-stop layer or back-channel into the main channel under a negative electric field. The hydrogen atoms act as shallow donors (which causes the carrier concentration in the channel to rise), causing the threshold voltage (VTH) to shift in the negative direction. Hydrogen diffusion from the overlap of the source/drain and gate electrodes to the channel center caused by the tip electric field induces a significant barrier lowering and VTH shifts in a short-channel device. However, under negative bias stress (NBS) in ambient moisture, the negative VTH shift is more obvious in short- than in long-channel devices, indicating suppressed hydrogen diffusion in long-channel devices. This is attributed to the electrolysis of water by the tip electric field at the source, drain, and gate electrodes, which causes hydrogen to diffuse to the center of the channel. Here, a novel physical model of the capacitance-voltage (C-V) electrical property changes under ambient moisture is proposed, based on the early appearance of abnormalities in the C-V measurements. The electrolysis of water caused by the tip electric field and electrical abnormalities caused by hydrogen diffusion into the a-IGZO active layer are explained by this model. A secondary-ion mass spectrometry analysis shows that hydrogen content in the channel generally increases under NBS in ambient moisture. The degradation behavior due to moisture in a-IGZO is clarified. Thus, inhibiting the tip electric field may benefit future flexible-display and gas-sensing applications.

Carrier Transport and Recombination Mechanism in Blue Phosphorescent Organic Light-Emitting Diode with Hosts Consisting of Cabazole- and Triazole-Moiety.

In this study, we demonstrated a blue phosphorescent organic light-emitting diode (BPOLED) based on a host with two carbazole and one trizole (2CbzTAZ) moiety, 9,9'-(2-(4,5-diphenyl-4H-1,2,4-triazol-3-yl)-1,3-phenylene)bis(9H-carbazole), that exhibits bipolar transport characteristics. Compared with the devices with a carbazole host (N,N'-dicarbazolyl-3,5-benzene, (mCP)), triazole host (3-(biphenyl-4-yl)-5-(4-tert-butylphenyl)-4-phenyl-4H-1,2,4-triazole, (TAZ)), or a physical mixture of mCP:TAZ, which exhibit hole, electron, and bipolar transport characteristics, respectively, the BPOLED with the bipolar 2CbzTAZ host exhibited the lowest driving voltage (6.55 V at 10 mA/cm2), the highest efficiencies (maximum current efficiency of 52.25 cd/A and external quantum efficiency of 23.89%), and the lowest efficiency roll-off, when doped with bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) as blue phosphor. From analyses of light leakage of the emission spectra of electroluminescence, transient electroluminescence, and partially doped OLEDs, it was found that the recombination zone was well confined inside the emitting layer and the recombination rate was most efficient in a 2CbzTAZ-based OLED. For the other cases using mCP, TAZ, and mCP:TAZ as hosts, electrons and holes transported with different routes that resulted in carrier accumulation on different organic molecules and lowered the recombination rate.

Effects of statins on all-cause mortality at different low-density-lipoprotein cholesterol levels in Asian patients with type 2 diabetes.

OBJECTIVE: To investigate the effects of statins on all-cause mortality risk at different low-density lipoprotein cholesterol (LDL-C) levels, and to compare the mortality risk between statin users and non-users with identical LDL-C levels in a type 2 diabetes cohort. METHODS: In total, 10,582 outpatients aged ≥18 years with type 2 diabetes mellitus (T2DM) between 2009 and 2012 were enrolled in this retrospective cohort study in central Taiwan. All-cause mortality events were followed up until the end of 2014. According to the medical records during the follow-up period, the patients were classified into statin (+) and statin (-) groups. Patients were categorized into different LDL-C segments based on their mean LDL-C levels during the 2.8-year follow-up. RESULTS: Non-cardiovascular mortality accounted for more than half the deaths. Overall, statin therapy significantly reduced the all-cause mortality risk in both univariable and multivariable models (hazard ratios = 0.39 and 0.38, respectively). Sub-group analyses showed that the lowest mortality risk occurred in the 80-89 mg/dL segment in the statin (-) group and in the 90-99 mg/dL segment in the statin (+) group. Statin therapy significantly reduced the mortality risk at all LDL-C levels except for low LDL-C (<60 mg/dL). CONCLUSIONS: In addition to reducing LDL-C levels, statin therapy reduced all-cause mortality risk in Taiwanese patients with T2DM. Statins further reduced the mortality risk at most LDL levels. However, at low LDL-C levels, the positive effects of statins may have been nullified.

A computed tomographic image study on the thickness of the infrazygomatic crest of the maxilla and its clinical implications for miniscrew insertion.

INTRODUCTION: The purpose of this study was to measure the thickness of the infrazygomatic (IZ) crest above the maxillary first molar at different angles and positions to the maxillary occlusal plane. These measurements were then used to derive clinical implications and guidance for inserting miniscrews in the IZ crest without injuring the mesiobuccal root of the maxillary first molar. METHODS: Computed tomographic images of 16 adults were used. For each subject, on the coronal slice of the computed tomographic image containing the IZ crest and mesiobuccal root of the maxillary first molar, the IZ crest thickness and the miniscrew insertion position were measured by postulating that the miniscrew would be inserted at each 5 degrees increment from 40 degrees to 75 degrees to the maxillary occlusal plane. RESULTS: The IZ crest thickness above the maxillary first molar ranged from 5.2 +/- 1.1 mm to 8.8 +/- 2.3 mm, measured at 40 degrees to 75 degrees to the maxillary occlusal plane and 13 to 17 mm above the maxillary occlusal plane. CONCLUSIONS: By adopting 6 mm as the minimal IZ crest thickness for sustaining a miniscrew well throughout treatment and avoiding injury to the mesiobuccal root of the maxillary first molar, the clinical implication for miniscrew placement in the IZ crest of an adult is to insert it 14 to 16 mm above the maxillary occlusal plane and the maxillary first molar at an angle of 55 degrees to 70 degrees to the maxillary occlusal plane.

Investigation of Ag-TiO2 Interfacial Reaction of Highly Stable Ag Nanowire Transparent Conductive Film with Conformal TiO2 Coating by Atomic Layer Deposition.

The atomic layer deposition (ALD) technique is applied to coat Ag nanowires (NWs) with a highly uniform and conformal TiO2 layer to improve the stability and sustainability of Ag NW transparent conductive films (TCFs) at high temperatures. The TiO2 layer can be directly deposited on Ag NWs with a surface polyvinylpyrrolidone (PVP) coat that acts a bed for TiO2 seeding in the ALD process. The ALD TiO2 layer significantly enhances the thermal stability at least 100 fold when aged between 200-400 °C and also provides an extra function of violet-blue light filtration for Ag NW TCFs. Investigation into the interaction between TiO2 and Ag reveals that the conformal TiO2 shell could effectively prevent Ag from 1D-to-3D ripening. However, Ag could penetrate the conformal TiO2 shell and form nanocrystals on the TiO2 shell surface when it is aged at 400 °C. According to experimental data and thermodynamic evaluation, the Ag penetration leads to an interlayer composed of mixed Ag-Ag2O-amorphous carbon phases and TiO2-x at the Ag-TiO2 interface, which is thought to be caused by extremely high vapor pressure of Ag at the Ag-TiO2 interface at a higher temperature (e.g., 400 °C).