Manipulation of Moiré Superlattice in Twisted Monolayer-multilayer Graphene by Moving Nanobubbles.

In the heterostructure of two-dimensional (2D) materials, many novel physics phenomena are strongly dependent on the Moiré superlattice. How to achieve the continuous manipulation of the Moiré superlattice in the same sample is very important to study the evolution of various physical properties. Here, in minimally twisted monolayer-multilayer graphene, we found that bubble-induced strain has a huge impact on the Moiré superlattice. By employing the AFM tip to dynamically and continuously move the nanobubble, we realized the modulation of the Moiré superlattice, like the evolution of regular triangular domains into long strip domain structures with single or double domain walls. We also achieved controllable modulation of the Moiré superlattice by moving multiple nanobubbles and establishing the coupling of nanobubbles. Our work presents a flexible method for continuous and controllable manipulation of Moiré superlattices, which will be widely used to study novel physical properties in 2D heterostructures.

Design, synthesis, and evaluation of VHL-based EZH2 degraders for breast cancer.

EZH2 (enhancer of zeste homolog 2) is one of the most important histone methyltransferases (HMTs), and overexpression of EZH2 can lead to proliferation, migration and angiogenesis of tumor cells. But most of EZH2 inhibitors are only effective against some hematologic malignancies and have poor efficacy against solid tumors. Here, we report the design, synthesis, and evaluation of highly potent proteolysis targeting chimeric (PROTACs) small molecules targeting EZH2. We developed a potent and effective EZH2 degrader P4, which effectively induced EZH2 protein degradation and inhibited breast cancer cell growth. Further studies showed that P4 can significantly decrease the degree of H3K27me3 in MDA-MB-231 cell line, induce apoptosis and G0/G1 phase arrest in Pfeiffer and MDA-MB-231 cell lines. Therefore, P4 is a potential anticancer molecule for breast cancer treatment.

Controlling the 2D Magnetism of CrBr3 by van der Waals Stacking Engineering.

The manipulation of two-dimensional (2D) magnetic order is of significant importance to facilitate future 2D magnets for low-power and high-speed spintronic devices. van der Waals stacking engineering makes promises for controllable magnetism via interlayer magnetic coupling. However, directly examining the stacking order changes accompanying magnetic order transitions at the atomic scale and preparing device-ready 2D magnets with controllable magnetic orders remain elusive. Here, we demonstrate the effective control of interlayer stacking in exfoliated CrBr3 via thermally assisted strain engineering. The stable interlayer ferromagnetic (FM), antiferromagnetic (AFM), and FM-AFM coexistent ground states confirmed by the magnetic circular dichroism measurements are realized. Combined with the first-principles calculations, the atomically resolved imaging technique reveals the correlation between magnetic order and interlayer stacking order in CrBr3 flakes unambiguously. A tunable exchange bias effect is obtained in the mixed phase of FM and AFM states. This work will introduce new magnetic properties by controlling the stacking order and sequence of 2D magnets, providing ample opportunities for their application in spintronic devices.

A Lightweight Algorithm for Insulator Target Detection and Defect Identification.

The accuracy of insulators and their defect identification by UAVs (unmanned aerial vehicles) in transmission-line inspection needs to be further improved, and the model size of the detection algorithm is significantly reduced to make it more suitable for edge-end deployment. In this paper, the algorithm uses a lightweight GhostNet module to reconstruct the backbone feature extraction network of the YOLOv4 model and employs depthwise separable convolution in the feature fusion layer. The model is lighter on the premise of ensuring the effect of image information extraction. Meanwhile, the ECA-Net channel attention mechanism is embedded into the feature extraction layer and PANet (Path Aggregation Network) to improve the recognition accuracy of the model for small targets. The experimental results show that the size of the improved model is reduced from 244 MB to 42 MB, which is only 17.3% of the original model. At the same time, the mAp of the improved model is 0.77% higher than that of the original model, reaching 95.4%. Moreover, the mAP compared with YOLOv5-s and YOLOX-s, respectively, is improved by 1.98% and 1.29%. Finally, the improved model is deployed into Jetson Xavier NX and run at a speed of 8.8 FPS, which is 4.3 FPS faster than the original model.

ZmHMA3, a Member of the Heavy-Metal-Transporting ATPase Family, Regulates Cd and Zn Tolerance in Maize.

The pollution of heavy metals is extremely serious in China, including zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd). Heavy-metal-transporting ATPase (HMA) belongs to a subfamily of the P-ATPase family, which absorbs and transports Zn, Cu, Pb, and Cd in plants. Here, we describe a ZmHMA-encoding HMA family protein that positively regulates Cd and Zn tolerance. The real-time fluorescence quantification (RT-PCR) results revealed that ZmHMA3 had a high expression in B73, and the expression of ZmHMA3 was sensitive to Cd in yeast cells, which was related to Cd accumulation in yeast. Additionally, the Arabidopsis thaliana homologous mutants of AtHMA2 showed Cd sensitivity compared with WT. The overexpressing ZmHMA3 plants showed higher tolerance under Cd and Zn stresses than the wild type. The overexpression of ZmHMA3 led to higher Cd and Zn accumulation in tissues based on the subcellular distribution analysis. We propose that ZmHMA3 improves maize tolerance to Cd and Zn stresses by absorbing and transporting Cd and Zn ions. This study elucidates the gene function of the ZmHMA3 response to Cd and Zn stress and provides a reference for improving the characteristics of heavy metals enrichment in existing maize varieties and the plant remediation technology of heavy-metal-contaminated soil.

Magnetism-Controllable Catalytic Activity of DNAzyme.

Controllable regulation of enzyme activity is an important prerequisite for the in-depth application of enzymes, especially in today's intelligent era. However, irreversible regulation and cumbersome operation make this goal difficult to achieve. Here, by adopting magnetism and a harmless, noncontact, and time- and space-controllable physical element, we developed a system that could conveniently and reversibly regulate the activity of DNAzyme. In this system, the strands of the DNAzyme could be stretched or folded by applying or removing a magnetic field. Thereby, the conformation-dependent endonuclease activity of the DNAzyme could be facilely switched between an "OFF" and "ON" state. This system provides a reusable platform for the control of enzyme catalytic activity through magnetism, which provides guidance for further application in some related scientific research, especially the regulation of the activity of conformation-dependent polymers (DNAzymes, aptamers, and peptides).

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy.

BACKGROUND: The development of diabetes vascular calcification (VC) is tightly associated with the inhibition of vascular smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 is expressed at higher level in the plasma of patients with coronary calcification. However, whether miR-32 mediates the function of macrophages in type 2 diabetes (T2D) VC is still unclear. METHODS: Wild-type (WT) and miR-32-/- mice were used in this study. qRT-PCR and western blotting were used to analyze gene expression. Flow cytometry was used to analyze the influence of glucose concentration on macrophage polarization. Nanoparticle tracking analysis (NTA), transmission electron microscopy, and confocal microscopy were used to identify macrophage extracellular vehicles (EVs). Immunofluorescence, in situ hybridization (ISH), immunohistochemistry, and alizarin red staining were used to analyze the influence of macrophage EVs on autophagy and calcification of the aorta of miR-32-/- mice. A luciferase assay was used to analyze the effect of miR-32 on myocyte enhancer factor 2D (Mef2d) expression. Co-IP combined with mass spectrometry (MS) and transcriptome sequencing was used to analyze the signalling pathway by which Mef2d acts in VSMC autophagy. RESULTS: We found that high glucose conditions upregulate miR-32 expression in macrophages and their EVs. Importantly, macrophages and their EVs promote VSMC osteogenic differentiation and upregulate miR-32 expression in VSMCs. Moreover, miR-32 mimics transfection promoted osteogenic differentiation and inhibited autophagy in VSMCs. In vitro and in vivo experiments showed that Mef2d is the key target gene of miR-32 that inhibits VSMC autophagy. Furthermore, MS and transcriptome sequencing found that cGMP-PKG is an important signalling pathway by which Mef2d regulates VSMC autophagy. In addition, after T2D miR-32-/- mice were injected with macrophage EVs via the caudal vein, miR-32 was detected in aortic VSMCs of miR-32-/- mice. Moreover, autophagy was significantly inhibited, and calcification was significantly enhanced in aorta cells. CONCLUSIONS: These results reveal that EVs are the key pathway by which macrophages promote T2D VC, and that EVs miR-32 is a key cause of autophagy inhibition in VSMCs.

Layer-Number-Dependent Antiferromagnetic and Ferromagnetic Behavior in MnSb_{2}Te_{4}.

MnBi_{2}Te_{4}, an intrinsic magnetic topological insulator, has shown layer-number-correlated magnetic and topological phases. More interestingly, in the isostructural material MnSb_{2}Te_{4}, the antiferromagnetic (AFM) and ferromagnetic (FM) states have been both observed in the bulk counterparts, which are also predicted to be topologically nontrivial. Revealing the layer-number-dependent magnetic properties of MnSb_{2}Te_{4} down to a single septuple layer (SL) is of great significance for exploring the topological phenomena. However, this is still elusive. Here, using the polar reflective magnetic circular dichroism spectroscopy, both the A-type AFM and FM behaviors are observed and comprehensively studied in MnSb_{2}Te_{4} down to a single SL limit. In A-type AFM MnSb_{2}Te_{4} flakes, an obvious odd-even layer-number effect is observed. An additional surface spin-flop (SSF) transition occurs in even-SL flakes with the number of layers larger than 2. With the AFM linear-chain model, we identify that the even-SL flakes stabilize in a collinear state between the SSF transition and the spin-flop transition due to their appropriate energy ratio between the magnetic-field-scale anisotropy and interlayer interaction. In FM MnSb_{2}Te_{4} flakes, we observe very different magnetic behaviors with an abrupt spin-flipping transition and very small saturation fields, indicating a weakened interlayer interaction. By revealing the rich magnetic states of few-SL MnSb_{2}Te_{4} on the parameter space of the number of layers, external magnetic field, and temperature, our findings pave the way for further quantum transport studies of few-SL MnSb_{2}Te_{4}.

Molecular cloning, inducible expression and function analysis of Epinephelus coioides Sec6 response to SGIV infection.

Exocyst complex component 3 Sec6 of mammals, one of the components of the exocyst complex, participates in numerous cellular functions, such as promoting cell migration and inhibiting apoptosis. In this study, the Sec6 was obtained from Epinephelus coioides, an economically important cultured fish. The full length of E. coioides Sec6 was 2655 bp including a 245 bp 5' UTR, a 154 bp 3' UTR, and a 2256 bp open reading frame (ORF) encoding 751 amino acids, with a molecular mass of 86.76 kDa and a theoretical pI of 5.57. Sec6 mRNA was detected in all the tissues examined, but the expression level is different in these tissues. Using fluorescence microscopy, Sec6 were distributed in both the nucleus and the cytoplasm. After SGIV infection, the expression of E. coioides Sec6 was significantly up-regulated in both trunk kidney and spleen response to Singapore grouper iridovirus (SGIV), an important pathogens of E. coioides. Sec6 could increase the SGIV-induced cytopathic effects (CPE), the expression of the SGIV genes VP19, LITAF, MCP, ICP18 and MCP, and the viral titers. Besides, E. coioides Sec6 significantly downregulated the promoter of NF-κB and AP-1, and inhibited the SGIV-induced apoptosis. The results demonstrated that E. coioides Sec6 might play important roles in SGIV infection.

Epinephelus coioides Hsp27 negatively regulates innate immune response and apoptosis induced by Singapore grouper iridovirus (SGIV) infection.

Heat shock proteins (Hsps) are important for maintaining protein homeostasis and cell survival. In this study, Hsp27 of Epinephelus coioides, an economically important marine fish in China and Southeast Asian countries, was characterized. E. coioides Hsp27 contains the consered ACD_HspB1_like domain and three p38 MAPK phosphorylation sites, located at Thr-13, Thr-60 and Ser-167. E. coioides Hsp27 was distributed in both the cytoplasm and nucleus, its mRNA was detected in all 14 tissues examined, and its expression was up-regulated after challenge with Singapore grouper iridovirus (SGIV), an important E. coioides pathogen. Over-expression of E. coioides Hsp27 significantly upregulated the expressions of the key SGIV genes (VP19, LITAF, MCP, and ICP18), downgraded the expressions of the E. coioides immune factors (IRF3, IRF7, ISG15, and TRAF6) and proinflammatory factors (TNF-α, IL-8), downgraded the activation of nuclear factor kappa-B (NF-κB) and activator protein-1 (AP-1), and substantially inhibited the cell apoptosis induced by SGIV infection. These data illustrated that E. coioides Hsp27 might be involved in SGIV infection by negatively regulating the innate immune response.

Whether the Research on Ethanol-Water Microstructure in Traditional Baijiu Should Be Strengthened?

Baijiu is a unique and traditional distilled liquor in China. Flavor plays a crucial rule in baijiu. Up to now, the research on the flavor of baijiu has progressed from the identification of volatile compounds to the research on key aroma compounds, but the release mechanism of these characteristic compounds is still unclear. Meanwhile, volatile compounds account for only a tiny fraction, whereas ethanol and water account for more than 98% of the content in baijiu. By summarizing the ethanol-water hydrogen bond structure in different alcoholic beverages, it was found that flavor compounds can affect the association strength of the ethanol-water hydrogen bond, and ethanol-water can also affect the interface distribution of flavor compounds. Therefore, the research on ethanol-water microstructure in baijiu is helpful to realize the simple visualization of adulteration detection, aging determination and flavor release mechanism analysis of baijiu, and further uncover the mystery of baijiu.

Melanoidins present in traditional fermented foods and beverages.

Traditional fermented foods and beverages (TFFB) are an important dietary component consumed in large quantities worldwide. Currently, much attention has been focused on the health benefits of TFFB. Melanoidins, a class of bioactive substance produced in the final stage of the Maillard reaction, not only have a significant impact on sensory properties of TFFB but also contribute to the health effects. Melanoidins formed in the fermentation system with a long reaction time at low temperature could be different from those obtained from high-temperature, short-duration roasted systems due to the multiple formative stages and involvement of microorganisms and enzymes. In this paper, the current state of knowledge regarding the formation, distribution, extraction and purification, physicochemical properties, structure characteristics, and biological activities of TFFB melanoidins are comprehensively reviewed, with predominant focus on TFFB that are typically brown like douchi, miso, cheonggukjang, soy sauce, huangjiu (Chinese rice wine), beer, vinegar, and sweet wine. The current challenges and prospective recommendations for the research of melanoidins in fermented systems are also presented. In future, people should pay more attention to the basic research on TFFB melanoidins, especially purification methods and formation mechanisms, further substantiation of health properties of TFFB melanoidins in vivo, and development of specific melanoidins to fulfill technological, productive, or health needs of consumers.

Scaling-up Atomically Thin Coplanar Semiconductor-Metal Circuitry via Phase Engineered Chemical Assembly.

Two-dimensional (2D) layered semiconductors, with their ultimate atomic thickness, have shown promise to scale down transistors for modern integrated circuitry. However, the electrical contacts that connect these materials with external bulky metals are usually unsatisfactory, which limits the transistor performance. Recently, contacting 2D semiconductors using coplanar 2D conductors has shown promise in reducing the problematic high contact resistance. However, many of these methods are not ideal for scaled production. Here, we report on the large-scale, spatially controlled chemical assembly of the integrated 2H-MoTe2 field-effect transistors (FETs) with coplanar metallic 1T'-MoTe2 contacts via phase engineered approaches. We demonstrate that the heterophase FETs exhibit ohmic contact behavior with low contact resistance, resulting from the coplanar seamless contact between 2H and 1T'-MoTe2 confirmed by transmission electron microscopy characterizations. The average mobility of the heterophase FETs was measured to be as high as 23 cm2 V-1 s-1 (comparable with those of exfoliated single crystals), due to the large 2H-MoTe2 single-crystalline domain size (486 ± 187 µm). By developing a patterned growth method, we realize the 1T'-MoTe2 gated heterophase FET array whose components of the channel, gate, and contacts are all 2D materials. Finally, we transfer the heterophase device array onto a flexible substrate and demonstrate the near-infrared photoresponse with high photoresponsivity (∼1.02 A/W). Our study provides a basis for the large-scale application of phase-engineered coplanar MoTe2 semiconductor-metal structure in advanced electronics and optoelectronics.

Millimeter-Scale Single-Crystalline Semiconducting MoTe2 via Solid-to-Solid Phase Transformation.

Among the Mo- and W-based two-dimensional (2D) transition metal dichalcogenides, MoTe2 is particularly interesting for phase-engineering applications, because it has the smallest free energy difference between the semiconducting 2H phase and metallic 1T' phase. In this work, we reveal that, under the proper circumstance, Mo and Te atoms can rearrange themselves to transform from a polycrystalline 1T' phase into a single-crystalline 2H phase in a large scale. We manifest the mechanisms of the solid-to-solid transformation by conducting density functional theory calculations, transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. The phase transformation is well described by the time-temperature-transformation diagram. By optimizing the kinetic rates of nucleation and crystal growth, we have synthesized a single-crystalline 2H-MoTe2 domain with a diameter of 2.34 mm, a centimeter-scale 2H-MoTe2 thin film with a domain size up to several hundred micrometers, and a seamless 1T'-2H MoTe2 coplanar homojunction. The 1T'-2H MoTe2 homojunction provides an elegant solution for ohmic contact of 2D semiconductors. The controlled solid-to-solid phase transformation in 2D limit provides a new route to realize wafer-scale single-crystalline 2D semiconductor and coplanar heterostructure for 2D circuitry.

Inhibition of Mitochondrial Fission Preserves Photoreceptors after Retinal Detachment.

Photoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgical procedures have been well developed to restore retinal structures, postoperative patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored. In this study, we show that after experimental retinal detachment induction, photoreceptors activate dynamin-related protein 1 (Drp1)-dependent mitochondrial fission pathway and subsequent apoptotic cascades. Mechanistically, endogenous reactive oxygen species (ROS) are necessary for Drp1 activation in vivo, and exogenous ROS insult is sufficient to activate Drp1-dependent mitochondrial fission in cultured photoreceptors. Accordingly, inhibition of Drp1 activity effectively preserves mitochondrial integrity and rescues photoreceptors. Collectively, our data delineate an ROS-Drp1-mitochondria axis that promotes photoreceptor degeneration in retinal diseased models.

The hypoxia-inducible factors HIF1α and HIF2α are dispensable for embryonic muscle development but essential for postnatal muscle regeneration.

Muscle satellite cells are myogenic stem cells whose quiescence, activation, self-renewal, and differentiation are influenced by oxygen supply, an environmental regulator of stem cell activity. Accordingly, stem cell-specific oxygen signaling pathways precisely control the balance between muscle growth and regeneration in response to oxygen fluctuations, and hypoxia-inducible factors (HIFs) are central mediators of these cellular responses. However, the in vivo roles of HIFs in quiescent satellite cells and activated satellite cells (myoblasts) are poorly understood. Using transgenic mouse models for cell-specific HIF expression, we show here that HIF1α and HIF2α are preferentially expressed in pre- and post-differentiation myoblasts, respectively. Interestingly, double knockouts of HIF1α and HIF2α (HIF1α/2α dKO) generated with the MyoDCre system in embryonic myoblasts resulted in apparently normal muscle development and growth. However, HIF1α/2α dKO produced with the tamoxifen-inducible, satellite cell-specific Pax7CreER system in postnatal satellite cells delayed injury-induced muscle repair due to a reduced number of myoblasts during regeneration. Analysis of satellite cell dynamics on myofibers confirmed that HIF1α/2α dKO myoblasts exhibit reduced self-renewal but more pronounced differentiation under hypoxic conditions. Mechanistically, the HIF1α/2α dKO blunted hypoxia-induced activation of Notch signaling, a key determinant of satellite cell self-renewal. We conclude that HIF1α and HIF2α are dispensable for muscle stem cell function under normoxia but are required for maintaining satellite cell self-renewal in hypoxic environments. Our insights into a critical mechanism in satellite cell homeostasis during muscle regeneration could help inform research efforts to treat muscle diseases or improve muscle function.

Implementation of human thermal comfort information in Köppen-Geiger climate classification-the example of China.

Köppen-Geiger climate classification (KGC) is accepted and applied worldwide. The climatic parameters utilised in KGC, however, cannot indicate human thermal comfort (HTC) conditions or air humidity (AH) conditions directly, because they are originally based on climatic effects on vegetation, instead of that on human body directly. In addition, HTC is driven by meteorological parameters together. Thus, the objective of this study is to preliminarily implement the HTC information and the AH information in KGC. Physiologically equivalent temperature (PET) has been chosen as the HTC index, and vapour pressure (VP) is for the quantification of AH conditions. In this preliminary study, 12 Chinese cities in total have been taken into account as the assumed representatives of 11 climate types. Basic meteorological data of each city with 3-h resolution in 2000-2012 has been analysed. RayMan model has been applied to calculate PET within the same time period. Each climate type has been described by frequencies of PET and frequencies of VP. For example, the Aw (Sanya) has the most frequent occurrence of thermally stressful conditions compared to other climate types: PET in 22 % points in time of the year was above 35 °C. The driest AH conditions existed in Dwc (Lhasa) and Dfb (Urumqi) with VP rarely above 18 hPa in the wettest month. Implementation of the HTC information and the additional AH information in each climate type of KGC can be helpful for the topics of human health, energy consumption, tourism, as well as urban planning.

Regulating N application for rice yield and sustainable eco-agro development in the upper reaches of Yellow River basin, China.

High N fertilizer and flooding irrigation applied to rice on anthropogenic-alluvial soil often result in N leaching and low recovery of applied fertilizer N from the rice fields in Ningxia irrigation region in the upper reaches of the Yellow River, which threatens ecological environment, food security, and sustainable agricultural development. This paper reported the regulating N application for rice yield and sustainable Eco-Agro development in the upper reaches of Yellow River basin. The results showed that reducing and postponing N application could maintain crop yields while substantially reducing N leaching losses to the environment and improving the nitrogen use efficiency. Considering the high food production, the minimum environmental threat, and the low labor input, we suggested that regulating N application is an important measure to help sustainable agricultural development in this region.

Maximizing arsenic trioxide's anticancer potential: Targeted nanocarriers for solid tumor therapy.

Arsenic trioxide (ATO) has gained significant attention due to its promising therapeutic effects in treating different diseases, particularly acute promyelocytic leukemia (APL). Its potent anticancer mechanisms have been extensively studied. Despite the great efficacy ATO shows in fighting cancers, drawbacks in the clinical use are obvious, especially for solid tumors, which include rapid renal clearance and short half-life, severe adverse effects, and high toxicity to normal cells. Recently, the emergence of nanomedicine offers a potential solution to these limitations. The enhanced biocompatibility, excellent targeting capability, and desirable effectiveness have attracted much interest. Therefore, we summarized various nanocarriers for targeted delivery of ATO to solid tumors. We also provided detailed anticancer mechanisms of ATO in treating cancers, its clinical trials and shortcomings as well as the combination therapy of ATO and other chemotherapeutic agents for reduced drug resistance and synergistic effects. Finally, the future study direction and prospects were also presented.

Tumor-derived microvesicles for cancer therapy.

Extracellular vesicles (EVs) are vesicles with lipid bilayer structures shed from the plasma membrane of cells. Microvesicles (MVs) are a subset of EVs containing proteins, lipids, nucleic acids, and other metabolites. MVs can be produced under specific cell stimulation conditions and isolated by modern separation technology. Due to their tumor homing and large volume, tumor cell-derived microvesicles (TMVs) have attracted interest recently and become excellent delivery carriers for therapeutic vaccines, imaging agents or antitumor drugs. However, preparing sufficient and high-purity TMVs and conducting clinical transformation has become a challenge in this field. In this review, the recent research achievements in the generation, isolation, characterization, modification, and application of TMVs in cancer therapy are reviewed, and the challenges facing therapeutic applications are also highlighted.