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Neuromorphic intelligent hardware technologies have undergone rapid advancement during the past decade, with the goal of building intelligent devices and systems capable of overcoming challenges associated with conventional hardware. Realization of neuromorphic intelligent hardware depends on major advances in materials science, condensed matter physics, device physics and engineering. As a revolutionary discovery, two-dimensional (2D) materials with atomically-thin thickness and exceptionally high tunability introduce a new physical paradigm and show great promise in the development of intelligent devices. Here, we give prominence to three categories of tunable properties (i.e., charge carrier, band structure, lattice structure) that are inherent for 2D materials and review their superiorities in constructing intelligent devices particularly in electronics and optoelectronics. Furthermore, we provide insight into how the unique physical mechanisms emerging in 2D materials offer a fertile ground for the design of diverse intelligence devices. [ABSTRACT FROM AUTHOR]

As China's digital transformation accelerates, there is growing interest in whether the digital economy can effectively boost green innovation in industrial enterprises and enable China's development to break through the constraints of resources and environment. Therefore, this study analyzes the data of A-share industrial listed enterprises (2011–2020). Results indicate that the digital economy promotes green innovation. The impact of the digital economy on green innovation varies significantly among different types of enterprises, with stronger effects on state-owned enterprises. Digital economy enhances green innovation via boosting public attention and optimizing energy structure. Therefore, playing the role of monitoring public attention, and optimizing energy use are key strategies to promote corporate green innovation. [ABSTRACT FROM AUTHOR]

Some small cell lung cancers (SCLCs) are highly sensitive to inhibitors of the histone demethylase LSD1. LSD1 inhibitors are thought to induce their anti-proliferative effects by blocking neuroendocrine differentiation, but the mechanisms by which LSD1 controls the SCLC neuroendocrine phenotype are not well understood. To identify genes required for LSD1 inhibitor sensitivity in SCLC, we performed a positive selection genome-wide CRISPR/Cas9 loss of function screen and found that ZFP36L1, an mRNA-binding protein that destabilizes mRNAs, is required for LSD1 inhibitor sensitivity. LSD1 binds and represses ZFP36L1 and upon LSD1 inhibition, ZFP36L1 expression is restored, which is sufficient to block the SCLC neuroendocrine differentiation phenotype and induce a non-neuroendocrine "inflammatory" phenotype. Mechanistically, ZFP36L1 binds and destabilizes SOX2 and INSM1 mRNAs, two transcription factors that are required for SCLC neuroendocrine differentiation. This work identifies ZFP36L1 as an LSD1 target gene that controls the SCLC neuroendocrine phenotype and demonstrates that modulating mRNA stability of lineage transcription factors controls neuroendocrine to non-neuroendocrine plasticity. LSD1 inhibition blocks the neuroendocrine phenotype of some small cell lung cancers (SCLCs). Here, a genome-wide CRISPR/Cas9 LSD1 inhibitor resistance screen identifies the mRNA-binding protein ZFP36L1 as a gene repressed by LSD1 that when restored inhibits SCLC neuroendocrine differentiation. [ABSTRACT FROM AUTHOR]

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-β induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling. The therapies for bone metastatic prostate cancer are limited and the underlying mechanisms are unclear. Here, the authors show that bone derived TGF-β induces acetylation of KLF5 (Ac-KLF5), and Ac-KLF5 promotes prostate cancer bone metastasis and resistance to docetaxel by upregulating CXCR4. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Myeloid-derived growth factor (MYDGF), mainly secreted by bone marrow-derived cells, has been known to promote glucagon-like peptide-1 production and improve glucose/lipid metabolism in mouse models of diabetes, but little is known about the functions of MYDGF in diabetic kidney disease (DKD). Here, we investigated whether MYDGF can prevent the progression of DKD. Methods: In vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of MYDGF on albuminuria and pathological glomerular lesions. We used streptozotocin-treated Mydgf knockout and wild-type mice on high fat diets to induce a model of DKD. Then, albuminuria, glomerular lesions and podocyte injury were evaluated in Mydgf knockout and wild-type DKD mice treated with adeno-associated virus-mediated Mydgf gene transfer. In vitro and ex vivo experiments, the expression of slit diaphragm protein nephrin and podocyte apoptosis were evaluated in conditionally immortalised mouse podocytes and isolated glomeruli from non-diabetic wild-type mice treated with recombinant MYDGF. Results: MYDGF deficiency caused more severe podocyte injury in DKD mice, including the disruption of slit diaphragm proteins (nephrin and podocin) and an increase in desmin expression and podocyte apoptosis, and subsequently caused more severe glomerular injury and increased albuminuria by 39.6% compared with those of wild-type DKD mice (p < 0.01). Inversely, MYDGF replenishment attenuated podocyte and glomerular injury in both wild-type and Mydgf knockout DKD mice and then decreased albuminuria by 36.7% in wild-type DKD mice (p < 0.01) and 34.9% in Mydgf knockout DKD mice (p < 0.01). Moreover, recombinant MYDGF preserved nephrin expression and inhibited podocyte apoptosis in vitro and ex vivo. Mechanistically, the renoprotection of MYDGF was attributed to the activation of the Akt/Bcl-2-associated death promoter (BAD) pathway. Conclusions/interpretation: The study demonstrates that MYDGF protects podocytes from injury and prevents the progression of DKD, providing a novel strategy for the treatment of DKD. [ABSTRACT FROM AUTHOR]

Prostate development depends on balanced cell proliferation and differentiation, and acetylated KLF5 is known to alter epithelial proliferation. It remains elusive whether post-translational modifications of transcription factors can differentially determine adult stem/progenitor cell fate. Here we report that, in human and mouse prostates, Klf5 is expressed in both basal and luminal cells, with basal cells preferentially expressing acetylated Klf5. Functionally, Klf5 is indispensable for maintaining basal progenitors, their luminal differentiation, and the proliferation of their basal and luminal progenies. Acetylated Klf5 is also essential for basal progenitors' maintenance and proper luminal differentiation, as deacetylation of Klf5 causes excess basal-to-luminal differentiation; attenuates androgen-mediated organoid organization; and retards postnatal prostate development. In basal progenitor-derived luminal cells, Klf5 deacetylation increases their proliferation and attenuates their survival and regeneration following castration and subsequent androgen restoration. Mechanistically, Klf5 deacetylation activates Notch signaling. Klf5 and its acetylation thus contribute to postnatal prostate development and regeneration by controlling basal progenitor cell fate. The role of the Klf5 in early and postnatal prostate development and in regeneration is unclear. Here, the authors show that Klf5 acetylation regulates and maintains luminal differentiation of prostate basal progenitors and is essential following androgen-induced regeneration. [ABSTRACT FROM AUTHOR]

Applying ultrasound (US) to drug delivery and disease therapy is important work. Sonodynamic therapy (SDT)-a comprehensive therapy using US and a sonosensitizer-exhibits antineoplastic activity in many tumors. In this study, we investigated the feasibility of using a new sonosensitizer (sinoporphyrin sodium, DVDMS) loaded into liposome-microbubble complexes (DLMBs) as a possible candidate to enhance SDT against breast cancer. DLMBs were synthesized via the biotin-avidin linkage and confirmed to have good US response. US-induced cavitation played a key role to trigger a boosted payload release from DLMBs and improve the cellular uptake and intratumoral diffusion of DVDMS to realize better SDT effect. The combination of DLMBs and US treatment resulted in significant changes to cell morphology, mitochondria damage, and cell apoptosis in vitro. In vivo, the combined treatment markedly inhibited tumor growth, which appeared to result from increased apoptosis and reduced proliferation activity. The significant increase in the antitumor effect of DLMBs plus US suggests their potential use as a new approach to promote the killing activity of SDT against breast cancer. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (GS-Rb1) is a well-known antioxidant derived from traditionally used herbal medicine ginseng. It has been suggested that reactive oxygen species (ROS) is involved in chronic kidney disease (CKD) in which GS-Rb1 may play a protective role. The aim of this study was to evaluate prospectively the effects of GS-Rb1 in patients with early chronic kidney disease. 197 patients who have been diagnosed with early CKD (stage 2 or 3) were recruited and randomly assigned to receive GS-Rb1 (500 mg daily oral administration, n = 103) or placebo ( n = 94) for consecutive 6 months. Analytical procedures performed at baseline, the end of the treatments, and 6 months after the treatments included renal function evaluation (creatinine and urea clearance), oxidative stress measurement, inflammation assessment, and lipid profile. Of 177 patients completing the study, the GS-Rb1 group ( n = 91) showed a positive response in significantly alleviating renal function impairments compared to the placebo group ( n = 86). In addition, GS-Rb1 treatment was effective in reducing the extent of oxidative stress and inflammation in CKD patients, whereas continued deterioration was observed in the placebo group. Thus, extended treatment of patients using GS-Rb1 may present an antioxidant-based approach to slow the progression of CKD at the early stages. [ABSTRACT FROM AUTHOR]

Optical chromatography is a powerful optofluidic technique enabling label-free fractionation of microscopic bioparticles from heterogenous mixtures. However, sophisticated instrumentation requirements for precise alignment of optical scattering and fluidic drag forces is a fundamental shortcoming of this technique. Here, we introduce a subwavelength thick (<200 nm) Optofluidic PlasmonIC (OPtIC) microlens that effortlessly achieves objective-free focusing and self-alignment of opposing optical scattering and fluidic drag forces for selective separation of exosome size bioparticles. Our optofluidic microlens provides a self-collimating mechanism for particle trajectories with a spatial dispersion that is inherently minimized by the optical gradient and radial fluidic drag forces working together to align the particles along the optical axis. We demonstrate that this facile platform facilitates complete separation of small size bioparticles (i.e., exosomes) from a heterogenous mixture through negative depletion and provides a robust selective separation capability for same size nanoparticles based on their differences in chemical composition. Unlike existing optical chromatography techniques that require complicated instrumentation (lasers, objectives and precise alignment stages), our OPtIC microlenses with a foot-print of 4 μm × 4 μm open up the possibility of multiplexed and high-throughput sorting of nanoparticles on a chip using low-cost broadband light sources. [ABSTRACT FROM AUTHOR]

Conventional microparticle transports by light or sound are realized along a straight line. Recently, this limit has been overcome in optics as the growing up of the self-accelerating Airy beams, which are featured by many peculiar properties, e.g., bending propagation, diffraction-free and self-healing. However, the bending angles of Airy beams are rather small since they are only paraxial solutions of the two-dimensional (2D) Helmholtz equation. Here we propose a novel micromanipulation by using acoustic Half-Bessel beams, which are strict solutions of the 2D Helmholtz equation. Compared with that achieved by Airy beams, the bending angle of the particle trajectory attained here is much steeper (exceeding 90o). The large-angle bending transport of microparticles, which is robust to complex scattering environment, enables a wide range of applications from the colloidal to biological sciences. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)-nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis., (© 2022. The Author(s).)