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Several studies reported the role of endoplasmic reticulum stress (ERS) in vascular calcification. High‐mobility group box‐1 (HMGB‐1) plays a substantial role in diabetes and its complications. However, relatively little information is available regarding the association between HMGB‐1 and calcification, and the underlying mechanism has still remained elusive. Therefore, in the present study, we attempted to indicate whether HMGB‐1 could promote vascular calcification via ERS in diabetes. After induction of diabetes by Streptozotocin (STZ), mice were treated with glycyrrhizin (Gly) or 4‐phenylbutyrate (4‐PBA). Mineral deposition was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR) and calcium assay. In cell experiments, calcification of vascular smooth muscle cells (VSMCs) was performed with Alizarin Red staining, alkaline phosphatase (ALP) activity and RT‐PCR. Expression and location of HMGB‐1 in aortic tissue were detected by Western blotting, immunocytochemistry (ICC) and immunohistochemistry (IHC). Diabetic mice demonstrated increased HMGB‐1 expression, ERS and vascular calcification. However, inhibition of HMGB‐1 with Gly or inhibition of ERS with 4‐PBA ameliorated the enhanced vascular calcification and ERS in diabetic mice. In vitro experiments unveiled that inhibition of HMGB‐1 attenuated advanced glycation end products (AGEs)‐induced ERS in VSMCs. In addition, AGEs promoted translocation and secretion of HMGB‐1 in VSMCs, which was reversed by 4‐PBA. Moreover, VSMCs exhibited increased mineralization and osteogenic gene expressions in response to HMGB‐1 and AGEs. However, inhibition of ERS with 4‐PBA partially, although noticeably, attenuated VSMC calcification induced by HMGB‐1. Thus, diabetes induced translocation and secretion of HMGB‐1 via ERS, which resulted in calcification in diabetic mice and in AGEs‐treated VSMCs.

Bats are natural reservoirs for zoonotic pathogens, yet the determinants of microbial persistence as well as the specific functionality of their immune system remain largely enigmatic. Their propensity to harbor viruses lethal to humans and/or livestock, mostly in absence of clinical disease, makes bats stand out among mammals. Defending against pathogens relies on avoidance, resistance, and/or tolerance strategies. In bats, disease tolerance has recently gained increasing attention as a prevailing host defense paradigm. We here summarize the current knowledge on immune responses in bats in the context of infection with zoonotic agents and discuss concepts related to disease tolerance. Acknowledging the wide diversity of bats, the broad spectrum of bat-associated microbial species, and immune-related knowledge gaps, we identify research priorities necessary to provide evidence-based proofs for disease tolerance in bats. Since disease tolerance relies on networks of biological processes, we emphasize that investigations beyond the immune system, using novel technologies and computational biology, could jointly advance our knowledge about mechanisms conferring bats reservoir abilities. Although disease tolerance may not be the “one fit all” defense strategy, deciphering disease tolerance in bats could translate into novel therapies and inform prevention of spillover infections to humans and livestock.

Smart window is an attractive option for efficient heat management to minimize energy consumption and improve indoor living comfort owing to their optical properties of adjusting sunlight. To effectively improve the sunlight modulation and heat management capability of smart windows, here, we propose a co-assembly strategy to fabricate the electrochromic and thermochromic smart windows with tunable components and ordered structures for the dynamic regulation of solar radiation. Firstly, to enhance both illumination and cooling efficiency in electrochromic windows, the aspect ratio and mixed type of Au nanorods are tuned to selectively absorb the near-infrared wavelength range of 760 to 1360 nm. Furthermore, when assembled with electrochromic W 18 O 49 nanowires in the colored state, the Au nanorods exhibit a synergistic effect, resulting in a 90% reduction of near-infrared light and a corresponding 5 °C cooling effect under 1-sun irradiation. Secondly, to extend the fixed response temperature value to a wider range of 30–50 °C in thermochromic windows, the doping amount and mixed type of W-VO 2 nanowires are carefully regulated. Last but not the least, the ordered assembly structure of the nanowires can greatly reduce the level of haze and enhance visibility in the windows. Smart windows offer more efficient sunlight modulation and heat management. Here, the authors propose a co-assembly strategy to produce smart windows that combine electrochromic and thermochromic functions with tunable components and ordered structures for dynamic solar radiation regulation.

The sun (∼6,000 K) and outer space (∼3 K) are two significant renewable thermodynamic resources for human beings on Earth. The solar thermal conversion by photothermal (PT) and harvesting the coldness of outer space by radiative cooling (RC) have already attracted tremendous interest. However, most of the PT and RC approaches are static and monofunctional, which can only provide heating or cooling respectively under sunlight or darkness. Herein, a spectrally self-adaptive absorber/emitter (SSA/E) with strong solar absorption and switchable emissivity within the atmospheric window (i.e., 8 to 13 μm) was developed for the dynamic combination of PT and RC, corresponding to continuously efficient energy harvesting from the sun and rejecting energy to the universe. The as-fabricated SSA/E not only can be heated to ∼170 °C above ambient temperature under sunshine but also be cooled to 20 °C below ambient temperature, and thermal modeling captures the high energy harvesting efficiency of the SSA/E, enabling new technological capabilities.

This study proposes the use of the voxel-based morphometry (VBM) technique to investigate structural alterations of the cerebral cortex in patients with strabismus and amblyopia (SA). Sixteen patients with SA and sixteen healthy controls (HCs) underwent magnetic resonance imaging. Original whole brain images were analyzed using the VBM method. Pearson correlation analysis was performed to evaluate the relationship between mean gray matter volume (GMV) and clinical manifestations. Receiver operating characteristic (ROC) curve analysis was applied to classify the mean GMV values of the SA group and HCs. Compared with the HCs, GMV values in the SA group showed a significant difference in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, bilateral parahippocampal gyrus, and left anterior cingulate cortex. The mean GMV value in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, and bilateral parahippocampal gyrus were negatively correlated with the angle of strabismus. The ROC curve analysis of each cerebral region confirmed the accuracy of the area under the curve. Patients with SA have reduced GMV values in some brain regions. These findings might help to reveal the potential pathogenesis of SA and its relationship with the atrophy of specific regions of the brain.

Neural progenitor cells （NPCs） can be induced from somatic cells by defined factors. Here we report that NPCs can be generated from mouse embryonic fibroblasts by a chemical cocktail, namely VCR （V, VPA, an inhibitor of HDACs; C, CHIR99021, an inhibitor of GSK3 kinases and R, Repsox, an inhibitor of TGF-Ⅱ pathways）, under a physiological hypoxic condition. These chemicalinduced NPCs （ciNPCs） resemble mouse brainderived NPCs re garding their proliferative and selfrenewing abilities, gene expression profiles, and multipotency for different neu roectodermal lineages in vitro and in vivo. Further experiments reveal that alternative cocktails with inhibitors of histone deacetylation, glycogen synthase kinase, and TGF-β pathways show similar efficacies for ciNPC induction. Moreover, ciNPCs can also be induced from mouse tailtip fibroblasts and human urinary cells with the same chemi cal cocktail VCR. Thus our study demonstrates that lineagespecific conversion of somatic cells to NPCs could be achieved bv chemical cocktails without introducina exoaenous factors.

Mitochondria are the critical organelles for energy metabolism and cell survival in eukaryotic cells. Recent studies demonstrated that mitochondria can intercellularly transfer between mammalian cells. In neural cells, astrocytes transfer mitochondria into neurons in a CD38-dependent manner. Here, using co-culture system of neural cell lines, primary neural cells, and human pluripotent stem cell (hPSC)-derived neural cells, we further revealed that mitochondria dynamically transferred between astrocytes and also from neuronal cells into astrocytes, to which CD38/cyclic ADP-ribose signaling and mitochondrial Rho GTPases (MIRO1 and MIRO2) contributed. The transfer consequently elevated mitochondrial membrane potential in the recipient cells. By introducing Alexander disease (AxD)-associated hotspot mutations (R79C, R239C) into GFAP gene of hPSCs and subsequently inducing astrocyte differentiation, we found that GFAP mutations impaired mitochondrial transfer from astrocytes and reduced astrocytic CD38 expression. Thus, our study suggested that mitochondria dynamically transferred between neural cells and revealed that AxD-associated mutations in GFAP gene disrupted the astrocytic transfer, providing a potential pathogenic mechanism in AxD.

One of the main characteristics of optical imaging systems is spatial resolution, which is restricted by the diffraction limit to approximately half the wavelength of the incident light. Along with the recently developed classical super-resolution techniques, which aim at breaking the diffraction limit in classical systems, there is a class of quantum super-resolution techniques which leverage the non-classical nature of the optical signals radiated by quantum emitters, the so-called antibunching super-resolution microscopy. This approach can ensure a factor of n improvement in the spatial resolution by measuring the n -th order autocorrelation function. The main bottleneck of the antibunching super-resolution microscopy is the time-consuming acquisition of multi-photon event histograms. We present a machine learning-assisted approach for the realization of rapid antibunching super-resolution imaging and demonstrate 12 times speed-up compared to conventional, fitting-based autocorrelation measurements. The developed framework paves the way to the practical realization of scalable quantum super-resolution imaging devices that can be compatible with various types of quantum emitters. Quantum super-resolution techniques take advantage of the non-classical nature of the quantum emitters, but are time-consuming. Here, the authors present a machine learning-assisted approach for fast antibunching-based super-resolution imaging, with a 12-fold speed up over the conventional approach

This study aimed to determine the correlation between HIF-1α and miR-27a expression and to evaluate the effect of inhibition of HIF-1α expression on miR-27a expression and drug resistance in gastric cancer (GC). In the present study, real time-PCR and Western blot were performed to detect the expression of HIF-1α in GC tissues and cell lines. Then, OCUM-2MD3/L-OHP cells were transfected with HIF-1α-siRNA, a miR-27a mimic or pcDNA-HIF-1α, and cell survival was determined via the MTT assay. The expression of HIF-1α, miR-27a, and MDR-related genes was measured via real time-PCR and Western blot. ChIP and dual luciferase activity assays were performed to assess the transcriptional regulation of HIF-1α and miR-27a. The results revealed that transfection with HIF-1α-siRNA markedly decreased the levels of miR-27a, resulting in dramatically enhanced inhibition of the proliferation rate of OCUM-2MD3/L-OHP cells. Compared to non-transfected cells, the survival rate was significantly reduced in the cells transfected with HIF-1α-siRNA after treatment with L-OHP. The cell survival rate was significantly increased in OCUM-2MD3/L-OHP cells transfected with the miR-27a mimic, whereas HIF-1α overexpression did not result in any clear change in cell survival. The results of the dual luciferase activity assay demonstrated that HIF-1α enhances the transcriptional activity of the miR27a promoter in cells transfected with a reporter plasmid containing the upstream promoter region of miR27a together with pcDNA-HIF-1α. ChIP analysis suggested that HIF-1α directly binds to the promoter region of miR27a. Inhibition of HIF-1α or miR27a expression decreased MDR1/P-gp, LRP, and Bcl-2 expression in OCUM-2MD3/L-OHP cells. Thus, we found that HIF-1α is closely associated with MDR in GC and that HIF-1α may suppress MDR1/P-gp, LRP and Bcl-2 expression by inhibiting miR-27a expression.

The Japanese encephalitis virus (JEV) is a Culex mosquito-borne flavivirus and is the pathogenic agent of Japanese encephalitis, which is the most important type of viral encephalitis in the world. Macrophages are a type of pivotal innate immunocyte that serve as sentinels and respond quickly to pathogen invasions. However, some viruses like JEV can hijack macrophages as a refuge for viral replication and immune escape. Despite their crucial involvement in early JEV infection, the transcriptomic landscapes of JEV-infected macrophages are void. Here, by using an in situ JEV infection model, we investigate the transcriptomic alteration of JEV-infected peritoneal macrophages. We found that, upon JEV infection, the macrophages underwent M1 polarization and showed the drastic activation of innate immune and inflammatory pathways. Interestingly, almost all the programmed cell death (PCD) pathways were activated, especially the apoptosis, pyroptosis, and necroptosis pathways, which were verified by the immunofluorescent staining of specific markers. Further transcriptomic analysis and TUNEL staining revealed that JEV infection caused apparent DNA damage. The transcriptomic analysis also revealed that JEV infection promoted ROS and RNS generation and caused oxidative stress, which activated multiple cell death pathways. Our work uncovers the pivotal pathogenic roles of oxidative stress and multiple PCD pathways in JEV infection, providing a novel perspective on JEV–host interactions.