RNF167-mediated ubiquitination of Tollip inhibits TNF-α-triggered NF-κB and MAPK activation.

Toll-interacting protein (Tollip) is a multifunctional regulator in cellular activities. However, whether its functions are subjected to post-translational modifications remains elusive. Here, we identified ubiquitination as a post-translational modification on Tollip. We found that Tollip interacted with ring finger protein 167 (RNF167) through its C-terminal coupling of ubiquitin to ER degradation (CUE) domain, and RNF167 functioned as the potential E3 ligase to attach K33-linked poly-ubiquitin chains to the Lys235 (K235) site of Tollip. Furthermore, we discovered Tollip could inhibit TNF-α-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation, and substitution of Lys235 on Tollip to arginine failed to suppress TNF-α-NF-κB/MAPK (JNK) cascades, revealing the role of Tollip and its ubiquitination in NF-κB/MAPK pathways. Thus, our study reveals the novel biological function of Tollip and RNF167-dependent ubiquitination of Tollip in TNF-α signaling.

10×10 Gbs directly modulated DFB laser array based on the REC technique.

We proposed and experimentally demonstrated a directly modulated distributed feedback (DFB) laser array with a transmission rate of 100 Gbps (10c h a n n e l s×10G b p s). The grating design is based on the reconstruction equivalent chirp (REC) technique, which enables precise control of the channel wavelength spacing to 100 GHz, as specified in the ITU-DWDM standard. DFB laser arrays incorporating the REC technique demonstrate excellent consistency performance, with a side-mode suppression ratio exceeding 48 dB, threshold current of approximately 20 mA, and modulation bandwidth of greater than 13 GHz at a bias current of 100 mA. We evaluated the laser's performance by loading a 10 Gbps nonreturn-to-zero signal onto the laser using direct modulation and transmitting it over a 10 km single-mode fiber. Based on our experimental results, the proposed DFB laser array is promising to be utilized in the next generation of low-cost, 100 Gbps DWDM communication systems.

Experimental demonstration of a photonic convolutional accelerator based on a monolithically integrated multi-wavelength distributed feedback laser.

We propose and experimentally demonstrate a simple and energy-efficient photonic convolutional accelerator based on a monolithically integrated multi-wavelength distributed feedback semiconductor laser using the superimposed sampled Bragg grating structure. The photonic convolutional accelerator operates at 44.48 GOPS for one 2 × 2 kernel with a convolutional window vertical sliding stride of 2 and generates 100 images of real-time recognition. Furthermore, a real-time recognition task on the MNIST database of handwritten digits with a prediction accuracy of 84% is achieved. This work provides a compact and low-cost way to realize photonic convolutional neural networks.

Nanosecond tunable laser for the all-optical switching network.

The optically switched network can offset the increasing gap between datacenter traffic growth and electrical switch capacity due to the slowdown of Moore's law. Ultra-high-speed wavelength tunable lasers are especially vital for the high integration and performance improvement of the all-optical switching system. In this paper, a fast tunable laser based on a laser array is realized. The 2×8 matrix structure of the laser array is fabricated by the reconstruction-equivalent-chirp (REC) technique. Aiming at the 2×8 array, a drive control system is designed to provide stable and fast switching, to achieve high-speed switching of the laser wavelength, and to keep the wavelength stable after switching. The simulation and experimental results show that the switching time between any two wavelength channels of the laser is less than 10 ns. The switching time of any two channels of the laser can be reduced by 2-3 ns after the pre-emphasis processing of the electrical signal.

V1-Cal hydrogelation enhances its effects on ventricular remodeling reduction and cardiac function improvement post myocardial infarction.

Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1-Cal has shown remarkable therapeutic effects on ML However, using V1-Cal to improve long-term cardiac function after MI is presently limited by its short half-life. Herein, we co-assembled V1-Cal with a well-known hydrogelator Nap-Phe-Phe-Tyr (NapFFY) to obtain a new supramolecular hydrogel V1-Cal/NapFFY. We found that the hydrogel could significantly enhance the therapeutic effects of V1-Cal on ventricular remodeling reduction and cardiac function improvement in a myocardial infarction rat model. In vitro experiments indicated that co-assembly of V1-Cal with NapFFY significantly increased mechanic strength of the hydrogel, enabling a sustained release of V1-Cal for more than two weeks. In vivo experiments supported that sustained release of V1-Cal from V1-Cal/NapFFY hydrogel could effectively decrease the expression and activation of TRPV1, reduce apoptosis and the release of inflammatory factors in a MI rat model. In particular, V1-Cal/NapFFY hydrogel significantly decreased infarct size and fibrosis, while improved cardiac function 28 days post MI. We anticipate that V1-Cal/NapFFY hydrogel could be used clinically to treat MI in the near future.

Applications of Red Mud as a Masonry Material: A Review.

Red mud (RM) is a highly alkaline by-product produced by the aluminium industry. The total stockpile of RM in the world is evaluated to be close 4 billion tons, which caused serious soil and water pollution. The use of RM in masonry materials has proven to be a prospective strategy to alleviate the environmental problems caused by RM. During the past decades, various economical treatment methods have been developed for utilization of RM as a masonry material. There are two general categories of products using RM in masonry materials: sintered products and non-sintered products. In this review, the physicochemical properties of RM are introduced, and the different application scenarios for RM in masonry materials are summarized, which is valuable for solving the environmental problems caused by the accumulation of bauxite residue. Moreover, the potential environmental risks of utilizing RM are described. Finally, suggestions for solving the RM problem are proposed.

CLEC5A knockdown protects against cardiac dysfunction after myocardial infarction by suppressing macrophage polarization, NLRP3 inflammasome activation, and pyroptosis.

Increasing evidence has shown that the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptotic cell death play vital roles in the pathophysiology of myocardial infarction (MI), a common cardiovascular disease characterized by cardiac dysfunction. C-type lectin member 5A (CLEC5A) has been reported to be strongly associated with activation of the NLRP3 inflammasome and pyroptosis. In this study, an in vivo MI model was established by ligation of the left anterior descending coronary artery in male C57BL/6 mice, and CLEC5A knockdown was further achieved by intra-myocardial injection of adenovirus delivering shRNA-CLEC5A. CLEC5A was found to be highly expressed in the left ventricle of MI mice, while CLEC5A knockdown alleviated cardiac dysfunction in MI mice. In addition, MI-induced classical activation of macrophages was significantly inhibited after CLEC5A silencing. Additionally, CLEC5A knockdown dramatically inhibited MI-triggered activation of NLRP3 inflammasome, pyroptosis, and NF-κB signaling in the left ventricle of mice. In vitro experiments further validated that CLEC5A knockdown suppressed M1 polarization in LPS/IFNγ-stimulated RAW264.7 cells and inhibited the polarized RAW264.7-induced activation of NLRP3 inflammasome/pyroptosis signaling in co-cultured cardiomyocytes. In conclusion, CLEC5A knockdown protects against MI-induced cardiac dysfunction by regulating macrophage polarization, NLRP3 inflammasome, and cell pyroptosis.

Pharmacological postconditioning with sappanone A ameliorates myocardial ischemia reperfusion injury and mitochondrial dysfunction via AMPK-mediated mitochondrial quality control.

Pharmacological postconditioning (PPC), drug intervention before or during the early minutes of reperfusion, could stimulate cardioprotection as ischemic postconditioning. In this study, we examined whether PPC with sappanone A (SA), a homoisoflavanone with potent antioxidant and anti-inflammatory activity, has a protective effect on myocardial ischemia reperfusion injury (MIRI), and explored the underlying mechanism. A MIRI model was established using the Langendorff method. After 30 min of ischemia, isolated rat hearts were treated with SA at the onset of reperfusion to stimulate PPC. The changes in myocardial infarct size, mitochondrial function, mitochondrial biogenesis, mitophagy, and mitochondrial fission and fusion were detected. The results showed that SA postconditioning decreased the myocardial infarct size, inhibited the release of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and cardiac troponin (cTnI), as well as improved cardiac function, enhanced myocardial ATP content and mitochondrial complex activity, and prevented the loss of mitochondrial membrane potential and opening of mitochondrial permeability transition pore (mPTP). Mechanistically, we found that SA was an AMP-activated protein kinase (AMPK) activator, and SA postconditioning could facilitate mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) copy number and the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). In addition, it balanced mitochondrial dynamics by decreasing fission and increasing fusion, and enhanced mitophagy in an AMPK-dependent manner. Moreover, AMPK silencing abolished the cardioprotection of SA postconditioning. Collectively, our study demonstrated that SA postconditioning ameliorated MIRI and mitochondrial dysfunction by regulation of mitochondrial quality control via activating AMPK. This finding provides a new insight into pharmacological action and clinical use of SA.

Melatonin and regulation of autophagy: Mechanisms and therapeutic implications.

Mitochondria are essential subcellular units that generate basic energy for the cell, as well as influence Ca2+ flux, apoptosis, and cell signaling. Mitophagy can selectively remove impaired mitochondria to preserve mitochondrial function, which is crucial for normal cellular maintenance. Mitochondrial dysfunction and mitophagy are widely reported to be linked to various pathogeneses. In addition, there is increasing evidence regarding the beneficial role of melatonin in the regulation and intervention of mitophagy progression. In this review, we focus on specific pathological conditions, including ischemia/reperfusion injury (IRI), cancer and neurodegenerative diseases, and elucidate the essential role of melatonin in the modulation of mitophagy in each of these distinct disorders.

Asherman syndrome in adenomyosis treated with uterine artery embolization: incidence predictive factors.

PURPOSE: To investigate Asherman syndrome (AS) related to potential factors during uterine artery embolization (UAE) treatment of adenomyosis. MATERIALS AND METHODS: This is a retrospective analysis of 195 women with adenomyosis who underwent UAE treatment from 2009 to 2016. All preoperative and intraoperative risk-related potential factors of AS were recorded. And AS events were carefully monitored during follow-up (range, 0-15 months). Potential risk-related factors of AS events were determined via univariate and multivariate logistic regression analyses. RESULTS: The rate of AS events after UAE for adenomyosis was 12.82% (25/195). The univariate and multivariate analyses revealed the association of low vascularity with a significant risk for AS (P = 0.019). CONCLUSION: Patients with low vascularity of adenomyosis at the time of UAE are more likely to have AS. And adenomyosis patients with low vascularity should be carefully selected to undergo UAE treatment.

Temperature Difference Triggering Controlled Growth of All-Inorganic Perovskite Nanowire Arrays in Air.

All-inorganic perovskites have attracted increasing worldwide interest due to its significantly improved stability in atmospheric environment compared to organic-inorganic hybrid perovskites, which renders it infinitely applicable in many fields such as electronics, optoelectronics, and energy storage. However, all-inorganic perovskites have to confront the challenges from fabrication before their wide utilization in the aforementioned applications. Liquid-phase synthesis holds the advantage of mass production and easy modulation of composition but with the deficiencies of relatively low crystallinity and disordered products. Interestingly, gas-phase growth has complementary characteristics compared to the liquid-phase method. In this work, it is proposed that a novel temperature difference triggers growth strategy to integrate the merits of the liquid- and gas-phase methods, and the feasibility of this strategy via a simple lab-use hot plate is demonstrated. High quality all-inorganic perovskites, cesium lead halide (CsPbX3 ) nanowire arrays, can be epitaxially grown as in a gas-phase method, but at the same time, the composition of products can be easily modulated by predesigning the recipe of precursors as in the liquid-phase method on a large scale. Notably, the as-fabricated CsPbX3 perovskite nanowire arrays demonstrate excellent stability and good optoelectronic properties in air. It is believed that this novel strategy can strikingly prompt the development of perovskites fabrication and applications in future.

Generalized Self-Doping Engineering towards Ultrathin and Large-Sized Two-Dimensional Homologous Perovskites.

Two-dimensional (2D) homologous perovskites are arousing intense interest in photovoltaics and light-emitting fields, attributing to significantly improved stability and increasing optoelectronic performance. However, investigations on 2D homologous perovskites with ultrathin thickness and large lateral dimension have been seldom reported, being mainly hindered by challenges in synthesis. A generalized self-doping directed synthesis of ultrathin 2D homologous (BA)2 (MA)n-1 Pbn Br3n+1 (1

Quercetin on the properties of rice bran oil body: Focused surface charge, oxidative stability and digestive properties.

To further enhance the stability of rice bran oil body (RBOB) emulsions, this study examined the impact of various concentrations of quercetin (QU) on the microstructure, rheological properties, oxidative stability, and digestive properties of RBOB emulsions. The results indicated that by incorporating QU concentration, the particle size of RBOB emulsions could be significantly reduced to 300 nm; QU could improve the surface hydrophobicity, the emulsifying activity index and emulsification stability index of RBOB emulsions of 550, 0.078 m2/g and 50.78 min, respectively; the storage stability of RBOB emulsions was further improved; the higher concentration of QU could delay the oxidation of RBOB emulsions, among which, the 500 µmol/L concentration inhibited the strongest effect of oil oxidation. It also improved the thermal stability of RBOB emulsions. After gastrointestinal digestion, the free fatty acids release rate of RBOB emulsions with QU addition decreased to 14.68%, and RBOB emulsions were slowly hydrolyzed. Therefore, adding QU to RBOB helps to improve its stability and delay digestion.

Expression of genes encoding cytokines and corticotropin releasing factor are altered by citalopram in the hypothalamus of post-stroke depression rats.

OBJECTIVES: To establish a rat model of post-stroke depression (PSD), and examine expression of genes encoding corticotropin releasing factor (CRF), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α) in the hypothalamus of PSD rats. METHODS: Rats were subjected to middle cerebral artery occlusion (MCAO) and chronic mild unpredictable stress (CUMS). Open field test and sucrose preference were used to examine depressive-like behaviors. Observed changes in gene expression levels in the hypothalamus of PSD rats were evaluated. RESULTS: MCAO with CUMS resulted in reduction of sucrose preference and locomotor activity. Genes encoding TNF-α, IL-1ß and CRF were highly expressed in the hypothalamus of rats subjected to MCAO and CUMS. The antidepressant citalopram, a selective serotonin reuptake inhibitor, had inhibitory effects on the expression of the aforementioned genes. We observed a correlation between CRF and IL-1ß mRNA levels in the citalopram-treated group of rats. CONCLUSION: The etiology of PSD is associated with cytokine expression in the hypothalamus and with hypothalamic-pituitary-adrenal axis activity. Citalopram administration inhibited the expression of TNF-α and IL-1ß transcripts in the hypothalamus, suggesting that selective serotonin reuptake inhibitors may be appropriate for PSD therapy.

Dual delivery of an NF-κB inhibitor and IL-10 through supramolecular hydrogels polarizes macrophages and promotes cardiac repair after myocardial infarction.

The use of anti-inflammatory strategies has the potential to be a definitive treatment for ventricular remodeling post myocardial infarction (MI). The regulation of macrophage phenotypes by anti-inflammatory agents contributes to the alleviation of myocardial fibrosis. However, their poor retention rates severely affect treatment efficacy. Here, we propose a supramolecular compound, NapFFY, to co-assemble with IL-10 and SN50 as a novel anti-inflammatory SN50/IL-10/NapFFY hydrogel with cardioprotective properties. Results from the in vitro and in vivo experiments in murine cell line and rats, respectively, demonstrated that the SN50/IL-10/NapFFY hydrogel exhibits an ideal and sustained release of IL-10 and SN50. Intramyocardial injection of the SN50/IL-10/NapFFY hydrogel in a rat model of MI significantly inhibited the expression of proinflammatory cytokines. It promoted the polarization of M2 macrophages, which reduced cardiomyocyte apoptosis and improved vascularization at the border zones. Specifically, the SN50/IL-10/NapFFY hydrogel significantly improved heart function and ameliorated ventricular remodeling 28 days post MI. We envision that the SN50/IL-10/NapFFY hydrogel could serve as a new anti-inflammatory agent for the clinical treatment of MI in future studies. STATEMENT OF SIGNIFICANCE: Anti-inflammation is an ideal strategy for the treatment of ventricular remodeling post myocardial infarction (MI). SN50 and IL-10 have been shown to have diverse roles in antiinflammatory process, respectively. However, direct intravenous administration or intramyocardial injection of SN50 or IL-10 is not a viable option given its poor half-life in vivo. This study aimed to evaluate the synergistic cardioprotective effects of a supramolecular hydrogel loaded with an NF-κB inhibitor (SN50) and IL-10. Animal experiments showed that the SN50/IL-10/NapFFY hydrogels ameliorated the inflammatory microenvironment, and improved cardiac function to the infarct area in a rat model of MI. We anticipate that SN50/IL10NapFFY hydrogel could be used clinically to treat MI in the near future.

Glucosamine-loaded injectable hydrogel promotes autophagy and inhibits apoptosis after cartilage injury.

The ability of cartilage to regenerate and repair is limited. N-acetyl- d-glucosamine (GlcNAc) is a nutritional supplement commonly used to activate chondrocytes. To prolong the duration of action of GlcNAc and improve its curative effect after cartilage injury, a GlcNAc thermosensitive hydrogel is prepared based on Pluronic F127 (PF127). The physicochemical properties results indicate that this hydrogel is injectable and retards the release of GlcNAc. Further, the therapeutic benefits of GlcNAc hydrogel are detected through intra-articular injection in rat specimens with cartilage injury. Behavioral experiments results indicate that the rats treated with GlcNAc hydrogel had longer step lengths, smaller foot angles and slower fall times. Compared with the sham group, the expression of Sox9 was 1.5 times and the level of collagen II was 2.4 times in the hydrogel treated group. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining result confirmed that the GlcNAc hydrogel reduce apoptosis by about 50%. Our results of immunohistochemical staining, Western blotting assays and enzyme activity detection all suggested that GlcNAc hydrogel reduce the expression of cleaved-caspase3 and caspase8 (Compared to the sham group, the protein contents were reduced by about 50% in the GlcNAc hydrogel group). We also found that GlcNAc hydrogel activates autophagy through ERK signal pathway. The results of Western blotting indicated that GlcNAc hydrogel increase the levels of LC3B and Becline1 (hydrogel group & sham group, LC3B: 1.56 ± 0.07 & 1.00 ± 0.14; Becline1: 1.98 ± 0.07 & 1.00 ± 0.13). Whereas, the content of P62 reduced after GlcNAc hydrogel treatment, the relative level in sham group and hydrogel group are 1.00 ± 0.02 and 0.73 ± 0.06. Our results revealed that the number of P-ERK positive cells in the hydrogel group (57.36 ± 3.56%) was higher when compared with the sham (24.82 ± 2.72%). And, the ratio of P-ERK and ERK was higher than that in the sham group (1.48 ± 0.07 & 1.00 ± 0.08). The GlcNAc thermosensitive hydrogel is a promising and sustainable drug delivery system for intra-articular injection in the treatment of cartilage injury.

Improved water splitting efficiency of Au-NP-loaded Ga2O3 thin films in the visible region under strong coupling conditions.

We fabricate a novel photoanode consisting of TiO2/Au nanoparticles (Au-NPs)/Ga2O3/TiN/Au-film (TAGA), efficiently increasing light absorption and electron transfer from Au-NPs to Ga2O3 under modal strong coupling. A TiN thin layer deposited on an Au film enables stable high-temperature deposition of Ga2O3 onto the reflective Au film mirror. Modal strong coupling is observed when the resonance wavelength of the Ga2O3/TiN/Au-film Fabry-Pérot cavity overlaps with the plasmon resonance wavelength of Au-NPs partially inlaid in a thin TiO2 layer. Under strong coupling conditions, the light absorption and photoelectrochemical conversion efficiency in the visible region increased more than in the samples without coupling. In this structure, the TiO2 layer partially inlaying Au-NPs plays a vital role in effectively enhancing the coupling strength. We accomplish water splitting at zero bias potential by taking advantage of the intrinsically negative conduction band potential of Ga2O3.

Multimodal Imaging and Synergetic Chemodynamic/Photodynamic Therapy Achieved Using an NaGdF4 ,Yb,Er@ NaGdF4 ,Yb,Tm@NaYF4 @Fe-MOFs Nanocomposite.

Here, NaGdF4 ,Yb,Er@NaGdF4 ,Yb,Tm@NaYF4 core@shell@shell three-layer structure of upconversion nanoparticles (UCNPs) coated with Fe-Tetrakis (4-carboxyphenyl) porphine (TCPP) metal-organic frameworks (Fe-MOFs) nanocomposite (UCNPs@MOFs) was designed and constructed for multimodal imaging and synergetic chemodynamic therapy (CDT)/photodynamic therapy (PDT) of tumors. The UCNPs@MOFs were successfully applied for tumor cells imaging in vitro and in vivo in near-infrared (NIR) region. The doped Gd was used as contrast agent for the magnetic resonance imaging (MRI) of mouse tumors. The luminescence in the UV-vis region was absorbed by the Fe-MOFs to produce singlet oxygen (1 O2 ) for PDT. The Fe3+ doped in the MOFs can catalyze H2 O2 to produce oxygen and hydroxyl radical (⋅OH). Hydroxyl radical is used in CDT and cooperates with the 1 O2 of PDT. Based on the CDT/PDT synergistic effects, the UCNPs@MOFs nanocomposite had obviously enhanced tumor inhibitory efficiency in vivo. These results described that the asprared UCNPs@MOFs nanocomposite have great potential in the effective multimodal imaging and treatment of tumors.

MMP 9-instructed assembly of bFGF nanofibers in ischemic myocardium to promote heart repair.

Background: The only effective treatment for myocardial infarction (MI) is the timely restoration of coronary blood flow in the infarcted area, but further reperfusion exacerbates myocardial injury and leads to distal coronary no-reflow, which affects patient prognosis. Angiogenesis could be an important therapeutic strategy for re-establishing the blood supply to save the ischemic myocardium after MI. Basic fibroblast growth factor (bFGF) has been shown to promote angiogenesis. However, direct intravenous administration of bFGF is not a viable option given its poor half-life in vivo. Methods: Herein, we developed a peptide Lys-Lys-Pro-Leu-Gly-Leu-Ala-Gly-Phe-Phe (K2) to encapsulate bFGF to form bFGF@K2 micelle and proposed an enzyme-instructed self-assembly (EISA) strategy to deliver and slowly release bFGF in the ischemic myocardium. Results: The bFGF@K2 micelle exerted a stronger cardioprotective effect than free bFGF in a rat model of myocardial ischemia-reperfusion (MI/R). In vitro results revealed that the bFGF@K2 micelle could be cleaved by matrix metallopeptidase 9 (MMP-9) to yield bFGF@Nanofiber through amphipathic changes. In vivo experiments indicated that intravenous administration of bFGF@K2 micelle could lead to their restructuring into bFGF@Nanofiber and long term retention of bFGF in the ischemic myocardium of rat due to high expression of MMP-9 and assembly-induced retention (AIR) effect, respectively. Twenty-eight days after MI/R model establishment, bFGF@K2 micelle treatment significantly reduced fibrosis and improved cardiac function of the rats. Conclusion: We predict that our strategy could be applied in clinic for MI treatment in the future.

Room Temperature Phosphorescent (RTP) Thermoplastic Elastomers with Dual and Variable RTP Emission, Photo-Patterning Memory Effect, and Dynamic Deformation RTP Response.

Room temperature phosphorescent (RTP) polymers have advantages of strength, toughness, and processing and application flexibility over organic small molecular crystals, but the current RTP polymers are all from rigid plastics and involve chemical linkage and hydrogen and ionic bonds, and thermoplastic RTP elastomer has not been attempted and realized. Moreover, solution-processed films by simply mixing polymers and organic RTP materials can only show weak and single blue RTP. Here it is presented that such elastomer films, once thermomechanically plasticized, can emit bright and long-lived dual RTP. Moreover, they exhibit photo-activation memory effect, variable RTP colors and dynamic deformation RTP response. These results reveal that thermoplasticizing has altered the dispersion states and micro-environment of RTP molecules in matrix, and the cohesion of elastic polymer itself can also greatly restrict non-radiative relaxations to boost both blue mono-molecular and yellow micro-crystalline RTP. This work provides an effective and versatile processing strategy for tuning and enhancing the RTP properties of doped RTP polymers.