Differences in resting-state brain activity in first-episode drug-naïve major depressive disorder patients with and without suicidal ideation.

Despite altered brain activities being associated with suicidal ideation (SI), the neural correlates of SI in major depressive disorder (MDD) have remained elusive. We enrolled 82 first-episode drug-naïve MDD patients including 41 with SI and 41 without SI, as well as 41 healthy controls (HCs). Resting-state functional and structural MRI data were collected. The measures of fractional amplitude of low-frequency fluctuation (fALFF) and grey matter volume (GMV) were calculated and compared. Compared with HCs, patients with SI exhibited increased fALFF values in the right rectus gyrus and left medial superior frontal gyrus, middle frontal gyrus and precuneus. Decreased GMV in the right parahippocampal gyrus, insula and middle occipital gyrus and increased GMV in the left superior frontal gyrus were detected in patients with SI. In addition, patients without SI demonstrated increased fALFF values in the right superior frontal gyrus and decreased fALFF values in the right postcentral gyrus. Decreased GMV in the left superior frontal gyrus, right medial superior frontal gyrus, opercular part of inferior frontal gyrus, postcentral gyrus, fusiform gyrus and increased left supplementary motor area, superior occipital gyrus, right anterior cingulate gyrus and superior temporal gyrus were revealed in patients with SI. Moreover, in comparison with patients without SI, increased fALFF values were identified in the left precuneus of patients with SI. However, no significant differences were found in GMV between patients with and without SI. These findings might be helpful for finding neuroimaging markers predicting individual suicide risk and detecting targeted brain regions for effective early interventions.

Sphingosylphosphorylcholine alleviates pressure overload-induced myocardial remodeling in mice via inhibiting CaM-JNK/p38 signaling pathway.

Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 µM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 µM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax and phosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 µM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.

Enhanced light output from deep ultraviolet light-emitting diodes enabled by high-order modes on a photonic crystal surface.

The authors demonstrate the enhanced light output from 275-nm AlGaN-based deep ultraviolet (DUV) light-emitting diode (LED) structures via the in-plane modulation of shallow photonic crystal (PC) patterns that were fabricated on the p-AlGaN contact layer surface. The employed PC lattice constants are in the range of 270-780 nm, much larger than the fundamental Bragg order lattice constant (∼95 nm). As compared to the unpatterned sample, the intensity of the top (or bottom) emission can be enhanced by up to 331% (or 246%), attributed to the high-order coherent diffraction of the internal trapped light and also the Purcell enhancement of spontaneous emission. The findings in this Letter suggest an easier way for the realization of more energy-efficient DUV LEDs which offer the advantage of high emission for various applications in disinfection and sterilization.

Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 µM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor ß-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

Cu2+ -Anchored Carbon Nano-Photocatalysts for Visible Water Splitting to Boost Hydrogen Cuproptosis.

Both hydrogen (H2 ) and copper ions (Cu+ ) can be used as anti-cancer treatments. However, the continuous generation of H2 molecules and Cu+ in specific sites of tumors is challenging. Here we anchored Cu2+ on carbon photocatalyst (Cu@CDCN) to allow the continuous generation of H2 and hydrogen peroxide (H2 O2 ) in tumors using the two-electron process of visible water splitting. The photocatalytic process also generated redox-active Cu-carbon centers. Meanwhile, the Cu2+ residues reacted with H2 O2 (the obstacle to the photocatalytic process) to accelerate the two-electron process of water splitting and cuprous ion (Cu+ ) generation, in which the Cu2+ residue promoted a pro-oxidant effect with glutathione through metal-reducing actions. Both H2 and Cu+ induced mitochondrial dysfunction and intracellular redox homeostasis destruction, which enabled hydrogen therapy and cuproptosis to inhibit cancer cell growth and suppress tumor growth. Our research is the first attempt to integrate hydrogen therapy and cuproptosis using metal-enhanced visible solar water splitting in nanomedicine, which may provide a safe and effective cancer treatment.

High brightness and broad modulation bandwidth InGaN-based red micro-LEDs integrated with plasmonic gratings.

We propose red micro-LEDs integrated with plasmonic gratings, which demonstrate high efficiency and broad modulation bandwidth. The Purcell factor and external quantum efficiency (EQE) for an individual device can be improved up to 5.1 and 11%, respectively, due to the strong coupling between surface plasmons and multiple quantum wells. The cross talk effect between adjacent micro-LEDs can be efficiently alleviated as well, thanks to the high-divergence far-field emission pattern. Moreover, the 3-dB modulation bandwidth of the designed red micro-LEDs is predicted to be ∼ 528 MHz. Our results can be used to design high-efficiency and high-speed micro-LEDs for the applications of advanced light display and visible light communication.

Dapagliflozin attenuates pressure overload-induced myocardial remodeling in mice via activating SIRT1 and inhibiting endoplasmic reticulum stress.

Endoplasmic reticulum stress-mediated apoptosis plays a vital role in the occurrence and development of heart failure. Dapagliflozin (DAPA), a new type of sodium-glucose cotransporter 2 (SGLT2) inhibitor, is an oral hypoglycemic drug that reduces glucose reabsorption by the kidneys and increases glucose excretion in the urine. Studies have shown that DAPA may have the potential to treat heart failure in addition to controlling blood sugar. This study explored the effect of DAPA on endoplasmic reticulum stress-related apoptosis caused by heart failure. In vitro, we found that DAPA inhibited the expression of cleaved caspase 3, Bax, C/EBP homologous protein (CHOP), and glucose-regulated protein78 (GRP78) and upregulated the cardiomyoprotective protein Bcl-2 in angiotensin II (Ang II)-treated cardiomyocytes. In addition, DAPA promoted the expression of silent information regulator factor 2-related enzyme 1 (SIRT1) and suppressed the expression of activating transcription factor 4 (ATF4) and the ratios p-PERK/PERK and p-eIF2α/eIF2α. Notably, the therapeutic effect of DAPA was weakened by pretreatment with the SIRT1 inhibitor EX527 (10 µM). Simultaneous administration of DAPA inhibited the Ang II-induced transformation of fibroblasts into myofibroblasts and inhibited fibroblast migration. In summary, our present findings first indicate that DAPA could inhibit the PERK-eIF2α-CHOP axis of the ER stress response through the activation of SIRT1 in Ang II-treated cardiomyocytes and ameliorate heart failure development in vivo.

Preparation of boronic acid and carboxyl-modified molecularly imprinted polymer and application in a novel chromatography mediated hollow fiber membrane to selectively extract glucose from cellulose hydrolysis.

A novel boronic acid and carboxyl-modified glucose molecularly imprinted polymer were prepared through suspension polymerization, which is based on 1.0 mmol glucose as a template, 1.2 mmol methacrylamidophenylboronic acid, and 6.8 mmol methacrylic acids as monomers, 19 mmol ethyleneglycol dimethacrylate, and 1 mmol methylene-bis-acrylamide as crosslinkers. The prepared glucose-molecularly imprinted polymer had a particle size of 25-70 µm, and was thermally stable below 215°C, with a specific surface area of 174.82 m2/ g and average pore size of 9.48 nm. The best selectivity between glucose and fructose was 2.71 and the maximum adsorption capacity of glucose- molecularly imprinted polymer was up to 236.32 mg/ g which was consistent with the Langmuir adsorption model. The similar adsorption abilities in six successive runs and the good desorption rate (99.4%) verified glucose-molecularly imprinted polymer could be reused. It was successfully used for extracting glucose from cellulose hydrolysis. The adsorption amount of glucose was 2.61 mg/mL and selectivity between glucose and xylose reached 4.12. A newly established chromatography (glucose-molecularly imprinted polymer) mediated hollow fiber membrane method in time separated pure glucose from cellulose hydrolysates on a large scale, and purified glucose solution with a concentration of 3.84 mg/mL was obtained, which offered a feasible way for the industrial production of glucose from cellulose hydrolysates.

Electron-Beam-Driven III-Nitride Plasmonic Nanolasers in the Deep-UV and Visible Region.

Plasmonic nanolasers based on wide bandgap semiconductors are presently attracting immense research interests due to the breaking in light diffraction limit and subwavelength mode operation with fast dynamics. However, these plasmonic nanolasers have so far been mostly realized in the visible light ranges, or most are still under optical excitation pumping. In this work, III-nitride-based plasmonic nanolasers emitting from the green to the deep-ultraviolet (UV) region by energetic electron beam injection are reported, and a threshold as low as 8 kW cm-2 is achieved. A fast decay time as short as 123 ps is collected, indicating a strong coupling between excitons and surface plasmon. Both the spatial and temporal coherences are observed, which provide a solid evidence for exciton-plasmon coupled polariton lasing. Consequently, the achievements in III-nitride-based plasmonic nanolaser devices represent a significant step toward practical applications for biological technology, computing systems, and on-chip optical communication.

Hollow V-Doped CoMx (M = P, S, O) Nanoboxes as Efficient OER Electrocatalysts for Overall Water Splitting.

Hollow nanostructures with intricate interior and catalytic effects have been the focus of researchers in energy conversion and storage. Although tremendous efforts have been made, the fabrication of well-defined hollow nanostructures has been rarely reported due to the limitations of the synthetic methods. Herein, we have proposed a general synthetic strategy for the construction of V-doped CoMx (M = P, S, O) nanoboxes (NBs), where the doped V effectively modifies the electronic structure of CoMx to provide a favorable surface electrochemical environment for the adsorption of reaction intermediates (*O, *OH, and *OOH), leading to a significant enhancement in electrocatalytic performance. More importantly, the hollow nanostructures can expose abundant surface active areas and promote the chemical adsorption of reactants and intermediates, greatly contributing to the promotion of electrocatalytic performance. Impressively, the optimal V-doped CoS2 NBs show excellent electrocatalytic oxygen evolution reaction (OER) performance with an overpotential of only 290 mV at 10 mA cm-2, along with outstanding overall water-splitting performance. This work supplies pivotal insights for constructing high-performance OER catalysts on the basis of electronic and geometric engineering.

Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes.

Both the magnitude and duration of insulin signaling are important in executing its cellular functions. Insulin-induced degradation of insulin receptor substrate 1 (IRS1) represents a key negative feedback loop that restricts insulin signaling. Moreover, high concentrations of fatty acids (FAs) and glucose involved in the etiology of obesity-associated insulin resistance also contribute to the regulation of IRS1 degradation. The scavenger receptor CD36 binds many lipid ligands, and its contribution to insulin resistance has been extensively studied, but the exact regulation of insulin sensitivity by CD36 is highly controversial. Herein, we found that CD36 knockdown in C2C12 myotubes accelerated insulin-stimulated Akt activation, but the activated signaling was sustained for a much shorter period of time as compared with WT cells, leading to exacerbated insulin-induced insulin resistance. This was likely due to enhanced insulin-induced IRS1 degradation after CD36 knockdown. Overexpression of WT CD36, but not a ubiquitination-defective CD36 mutant, delayed IRS1 degradation. We also found that CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with cullin 7, a key component of the multisubunit cullin-RING E3 ubiquitin ligase complex. Moreover, dissociation of the Src family kinase Fyn from CD36 by free FAs or Fyn knockdown/inhibition accelerated insulin-induced IRS1 degradation, likely due to disrupted IRS1 interaction with CD36 and thus enhanced binding to cullin 7. In summary, we identified a CD36-dependent FA-sensing pathway that plays an important role in negative feedback regulation of insulin activation and may open up strategies for preventing or managing type 2 diabetes mellitus.

Characterization of grass carp (Ctenopharyngodon idella) beta-defensin 1: implications for its role in inflammation control.

Considering that fish grows in a complex aquatic environment, there is an increasing interest in fish ß-defensins, which is an important group of antimicrobial peptides (AMPs). In this study, grass carp (Ctenopharyngodon idella) ß-defensin 1 (gcdefb1) was isolated using homology cloning technology. Tissue distribution assay showed that gcdefb1 transcripts were expressed with the highest levels in brain and liver, followed by some mucous tissues. To examine gcDefb1 bioactivities, the recombinant gcDefb1 proteins fused with thioredoxin tag protein (Trx) (Trx-Defb1) were induced for production in Escherichia coli Rosetta-gami2(DE3)pLysS under optimal expression conditions. The antibacterial activity of Trx-Defb1 against Aeromonas hydrophila was assessed and its minimum inhibitory concentration (MIC) was 36 µM. Interestingly, Trx-Defb1 significantly inhibited LPS-induced Tnf-α (gcTnf-α) secretion and nitric oxide production in grass carp head kidney monocytes/macrophages (HKM), although Trx-Defb1 alone had no effect. Our studies provide the first evidence of fish ß-defensin 1 engaging in both antimicrobial and inflammation suppression process.

Vertically Emitting Indium Phosphide Nanowire Lasers.

Semiconductor nanowire (NW) lasers have attracted considerable research effort given their excellent promise for nanoscale photonic sources. However, NW lasers currently exhibit poor directionality and high threshold gain, issues critically limiting their prospects for on-chip light sources with extremely reduced footprint and efficient power consumption. Here, we propose a new design and experimentally demonstrate a vertically emitting indium phosphide (InP) NW laser structure showing high emission directionality and reduced energy requirements for operation. The structure of the laser combines an InP NW integrated in a cat's eye (CE) antenna. Thanks to the antenna guidance with broken asymmetry, strong focusing ability, and high Q-factor, the designed InP CE-NW lasers exhibit a higher degree of polarization, narrower emission angle, enhanced internal quantum efficiency, and reduced lasing threshold. Hence, this NW laser-antenna system provides a very promising approach toward the achievement of high-performance nanoscale lasers, with excellent prospects for use as highly localized light sources in present and future integrated nanophotonics systems for applications in advanced sensing, high-resolution imaging, and quantum communications.

Low-threshold ultraviolet stimulated emissions from large-sized single crystalline ZnO transferable membranes.

Wide-bandgap inorganic semiconductors based ultraviolet lasers bring versatile applications with significant advantages including low-power consumption, high-power output, robustness and long-term operation stability. However, flexible membrane lasers remain challenging predominantly due to the need for a lattice matched supporting substrate. Here, we develop a simple laser liftoff process to make freestanding single crystalline ZnO membranes that demonstrate low-threshold ultraviolet stimulated emissions together with large sized dimension (> 2 mm), ultralow-weight (m/A<15 g/m2) and excellent flexibility. The 2.6 µm-thick crack-free ZnO membrane exhibits well-retained single crystallinity and enhanced excitonic emissions while the defect-related emissions are completely suppressed. The inelastic exciton-exciton scattering stimulated emissions with increased spontaneous emission rate is obtained with a reduced threshold of 0.35 MW/cm2 in the ZnO membrane transferred onto a flexible polyethylene naphthalate substrate. Theoretical simulations reveal that it is a synergetic effect of the increased quantum efficiency via Purcell effect and the improved optical gain due to vertical directional waveguiding of the membrane, which functions as a Fabry-Perot photonic resonator due to the refractive index contrast at ZnO-air boundaries. With simple architecture, efficient exciton recombination and easy fusion with waveguide system, the ZnO membranes provide an alternative platform to develop compact low-threshold ultraviolet excitonic lasers.

Development of a highly specific HER2 monoclonal antibody for immunohistochemistry using protein microarray chips.

HER2 is an orphan receptor tyrosine kinase of the EGFR families and is considered to be a key tumor driver gene [1]. Breast cancer and gastric cancer with HER2 amplification can be effectively treated by its neutralizing antibody, Herceptin. In clinic, Immunohistochemistry (IHC) was used as the primary screening method to diagnose HER2 amplification [2]. However, recent evidence suggested that the frequently used rabbit HER2 antibody 4B5 cross reacted with another family member HER4 [3]. IHC staining with 4B5 also indicated that there was strong non-specific cytoplasmic and nuclear signals in normal gastric mucosal cells and some gastric cancer samples. Using a protein lysate array which covers 85% of the human proteome, we have confirmed that the 4B5 bound to HER4 and a nuclear protein ZSCAN18 besides HER2. The non-specific binding accounts for the unexpected cytoplasmic and nuclear staining of 4B5 of normal gastric epithelium. Finally, we have developed a novel mouse HER2 monoclonal antibody UMAB36 with similar sensitivity to 4B5 but only reacted to HER2 across the 17,000 proteins on the protein chip. In 129 breast cancer and 158 gastric cancer samples, UMAB36 showed 100% sensitivity and specificity comparing to the HER2 FISH reference results with no unspecific staining in the gastric mucosa layer. Therefore, UMAB36 could provide as an alternative highly specific IHC reagent for testing HER2 amplification in gastric cancer populations.

Dietary safety assessment of genetically modified rice EH rich in ß-carotene.

This 90-day study aimed to assess the dietary safety of transgenic rice EH which is rich in ß-carotene. Two experimental groups of Sprague-Dawley rats were fed diets containing 45% rice flour of Zhonghua 11 rice and transgenic rice EH rich in ß-carotene, respectively. The reference group was fed a diet containing standard feed nutrition. During the trial period, each rat was weighed and the food intake was recorded twice a week. Their behaviors were observed daily. In the end, blood samples were obtained from all anesthetized rats to measure the hematologic and serum chemistry indicators. Growth performance, anatomy and pathology of all organs in each group were analyzed. Although a few parameters were found to be statistically significantly different across groups, they were within the normal reference range for this breed and age of rats. Therefore, the changes were not considered to be diet related. The results revealed that the transgenic rice EH rich in ß-carotene was as nutritious as Zhonghua 11 rice and showed a lack of biologically meaningful unintended effects.

Single nanowire green InGaN/GaN light emitting diodes.

Single nanowire (NW) green InGaN/GaN light-emitting diodes (LEDs) were fabricated by top-down etching technology. The electroluminescence (EL) peak wavelength remains approximately constant with an increasing injection current in contrast to a standard planar LED, which suggests that the quantum-confined Stark effect is significantly reduced in the single NW device. The strain relaxation mechanism is studied in the single NW LED using Raman scattering analysis. As compared to its planar counterpart, the EL peak of the NW LED shows a redshift, due to electric field redistribution as a result of changes in the cavity mode pattern after metallization. Our method has important implication for single NW optoelectronic device applications.

Bloch surface plasmon enhanced blue emission from InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods.

InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods were fabricated by using soft ultraviolet nanoimprint lithography. The intensity of light emission was found to be greatly enhanced due to the strong near-fields confined at the interface of Al/GaN and extended to the multiple quantum wells (MQWs) active region. The dynamics of carrier recombination and plasmon-enhanced Raman scattering were also investigated, providing a progressive view on the effective energy transfer between MQWs and surface plasmons.

Second-order surface-plasmon assisted responsivity enhancement in germanium nano-photodetectors with bull's eye antennas.

The enhancement of photo-response in nanometer-scale germanium photodetectors through bull's eye antennas capable of supporting 2nd-order Bloch surface plasmon modes is demonstrated in theory and experiment. A detailed numerical investigation reveals that the presence of surface wave and its constructive interference with the directly incident light are incorporated into the main mechanisms for enhancing transmission through the central nanoaperture. With a grating period of 1500 nm, the area-normalized responsivity can be enhanced up to 3.8 times at 2 V bias for a 780 nm laser. It provides an easier fabrication path for ultra-short wavelength operations especially in devices using optically denser materials.

Facile synthesis of Pt/Pd nanodendrites for the direct oxidation of methanol.

The demand for clean and energy-efficient fuel cell systems requires electrocatalysts with greater activity and stability. Here, we report a facile wet-chemical approach for the synthesis of high-quality three-dimensional (3D) Pt/Pd bimetallic nanodendrites. The simple and unique process developed here used oleylamine as a reducing agent, and hydrogen gas to control the morphology. The as-prepared Pt/Pd nanodendrites were characterized by transmission electron microscopy, x-ray diffraction and energy dispersive x-ray spectroscopy, cyclic voltammetry, linear sweep voltammetry and chronoamperometry. The nanodendrites showed superior electrocatalytic activity (609.565 mA mg(-1) Pt) for the oxidation of methanol compared with Pt nanoparticle electrocatalysts. This method could provide a general approach for the morphology-controlled synthesis of bimetallic Pt-based nanocatalysts, which are promising materials for applications in fuel cells.