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.

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.

High Thermoelectric Power Factors in Plastic/Ductile Bulk SnSe2 -Based Crystals.

The recently discovered plastic/ductile inorganic thermoelectric (TE) materials open a new avenue for the fabrication of high-efficiently flexible TE devices, which can utilize the small temperature difference between human body and environment to generate electricity. However, the maximum power factor (PF) of current plastic/ductile TE materials is usually around or less than 10 µW cm-1 K-2 , much lower than the classic brittle TE materials. In this work, a record-high PF of 18.0 µW cm-1 K-2 at 375 K in plastic/ductile bulk SnSe2 -based crystals is reported, superior to all the plastic inorganic TE materials and flexible organic TE materials reported before. The origin of such high PF is from the modulation of material's stacking forms and polymorph crystal structures via simultaneously doping Cl/Br at Se-site and intercalating Cu inside the van der Waals gap, leading to the significantly enhanced carrier concentrations and mobilities. An in-plane fully flexible TE device made of the plastic/ductile SnSe2 -based crystals is successfully developed to show a record-high normalized maximum power density to 0.18 W m-1 under a temperature difference of 30 K. This work indicates that the plastic/ductile material can realize high TE power factor to achieve large output electric power density in flexible TE technology.

Metabolic Glycoengineering-Programmed Nondestructive Capture of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are the "seeds" for malignant tumor metastasis, and they serve as an ideal target for minimally invasive tumor diagnosis. Abnormal glycolysis in tumor cells, characterized by glycometabolism disorder, has been reported as a universal phenomenon observed in various types of tumors. This provides a potential powerful tool for universal CTC capture. However, to the best of our knowledge, no metabolic glycoengineering-based CTC capture strategies have been reported. Here, we proposed a nondestructive CTC capture method based on metabolic glycoengineering and a nanotechnology-based proximity effect, allowing for highly specific, sensitive, and universal CTC capture. To achieve this goal, cells are first labeled with DNA tags through metabolic glycoengineering and then captured through a DNA tetrahedra-functionalized dual-tentacle magnetic nanodevice. Due to the difference in metabolic performance, only tumor cells are labeled with more densely packed DNA tags and captured through enhanced intermolecular interaction mediated by the proximity effect. In summary, we have constructed a versatile platform for nondestructive CTC capture, offering a novel perspective for the application of CTC liquid biopsy in tumor diagnosis and 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.

Long-term straw return improves cooked indica rice texture by altering starch structural, physicochemical properties in South China.

Straw return can improve rice eating quality by modifying starch formation from long-term field trials, whereas the relevant mechanisms are still unknown. A long-term field experiment, including straw removal (CK), straw burning return (SBR), and straw return (SR) was conducted to investigate the starch structure, physicochemical properties, and cooked rice textures of indica early- and late-rice. Compared with CK, SBR and SR enhanced relative crystallinity, amylopectin long chains in both rice seasons, and gelatinization temperatures in late rice. Compared to SBR, SR decreased protein content and amylopectin short chains but increased starch branching degree, breakdown, and stickiness, ultimately contributing to improved starch thermal and pasting properties. Meanwhile, SR decreased hardness, cohesiveness, and chewiness, resulting in cooked texture meliorated, which was mainly attributed to amylopectin chain length and starch granule size. The results suggest that SR increased cooked texture of indica rice by altering starch structural and physicochemical properties.

Vascular calcification: from the perspective of crosstalk.

Vascular calcification (VC) is highly correlated with cardiovascular disease morbidity and mortality, but anti-VC treatment remains an area to be tackled due to the ill-defined molecular mechanisms. Regardless of the type of VC, it does not depend on a single cell but involves multi-cells/organs to form a complex cellular communication network through the vascular microenvironment to participate in the occurrence and development of VC. Therefore, focusing only on the direct effect of pathological factors on vascular smooth muscle cells (VSMCs) tends to overlook the combined effect of other cells and VSMCs, including VSMCs-VSMCs, ECs-VMSCs, Macrophages-VSMCs, etc. Extracellular vesicles (EVs) are a collective term for tiny vesicles with a membrane structure that are actively secreted by cells, and almost all cells secrete EVs. EVs docked on the surface of receptor cells can directly mediate signal transduction or transfer their contents into the cell to elicit a functional response from the receptor cells. They have been proven to participate in the VC process and have also shown attractive therapeutic prospects. Based on the advantages of EVs and the ability to be detected in body fluids, they may become a novel therapeutic agent, drug delivery vehicle, diagnostic and prognostic biomarker, and potential therapeutic target in the future. This review focuses on the new insight into VC molecular mechanisms from the perspective of crosstalk, summarizes how multi-cells/organs interactions communicate via EVs to regulate VC and the emerging potential of EVs as therapeutic methods in VC. We also summarize preclinical experiments on crosstalk-based and the current state of clinical studies on VC-related measures.

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.

Magnetically-dressed CrSBr exciton-polaritons in ultrastrong coupling regime.

Over the past few decades, exciton-polaritons have attracted substantial research interest due to their half-light-half-matter bosonic nature. Coupling exciton-polaritons with magnetic orders grants access to rich many-body phenomena, but has been limited by the availability of material systems that exhibit simultaneous exciton resonances and magnetic ordering. Here we report magnetically-dressed microcavity exciton-polaritons in the van der Waals antiferromagnetic (AFM) semiconductor CrSBr coupled to a Tamm plasmon microcavity. Using angle-resolved spectroscopy, we reveal an exceptionally high exciton-photon coupling strength, up to 169 meV, demonstrating ultrastrong coupling that persists up to room temperature. By performing temperature-dependent spectroscopy, we show the magnetic nature of the exciton-polaritons in CrSBr microcavity as the magnetic order changes from AFM to paramagnetic. By applying an out-of-plane magnetic field, we achieve effective tuning of the polariton energy while maintaining the ultrastrong exciton-photon coupling strength. We attribute this to the spin canting process that modulates the interlayer exciton interaction.

Trust Your Good Friends: Source-Free Domain Adaptation by Reciprocal Neighborhood Clustering.

Domain adaptation (DA) aims to alleviate the domain shift between source domain and target domain. Most DA methods require access to the source data, but often that is not possible (e.g., due to data privacy or intellectual property). In this paper, we address the challenging source-free domain adaptation (SFDA) problem, where the source pretrained model is adapted to the target domain in the absence of source data. Our method is based on the observation that target data, which might not align with the source domain classifier, still forms clear clusters. We capture this intrinsic structure by defining local affinity of the target data, and encourage label consistency among data with high local affinity. We observe that higher affinity should be assigned to reciprocal neighbors. To aggregate information with more context, we consider expanded neighborhoods with small affinity values. Furthermore, we consider the density around each target sample, which can alleviate the negative impact of potential outliers. In the experimental results we verify that the inherent structure of the target features is an important source of information for domain adaptation. We demonstrate that this local structure can be efficiently captured by considering the local neighbors, the reciprocal neighbors, and the expanded neighborhood. Finally, we achieve state-of-the-art performance on several 2D image and 3D point cloud recognition datasets.

Analysis of the Dong bao Ye as sacred landscape and its Putative therapeutic mechanisms.

Humans have innately established close and profound ties with the, and through these relationships shaped many kinds of landscapes. Among these are sacred landscapes, which have drawn the attention of researchers due to their cultural significance. In the field of health geography, large-sized sacred regional landscapes are now the focus of studies for their therapeutic properties. However, few scholars have focused on small sacred landscape systems at the community level (constructed by local communities) or the physical and psycological health benefits that these landscapes offer to the local residents. These small-sized and widespread, but often hidden, sacred landscapes are closely tied to people's daily lives and work. They have evolved and grown over millennia to become critical sociocultural phenomena. This study takes the sacred bao ye landscape of the Dong people of China as the research subject. By adopting the case study approach, field research, semi-structured interviews, and textual analysis, it summarizes the types, geographical distribution, rituals and processes of bao ye as a sacred landscape of the Huanggang village in Guizhou Province, and concludes with an analysis of motivation and health benefits to the bao ye worship. In this paper we argue that bao ye is a sacred landscape system focusing on the healthy development of children, and constitutes a local belief developed in an isolated environment lacking medical resources, which remains in practice. The sacred landscape of bao ye offers a therapeutic environment, providing children with increased opportunities to engage with and build deep connections to nature. Thruogh this process children may develop a bond with nature that inspires them to protect nature on their own accord. We argue that bao ye offers an important case study for understanding the landscape-people-healing interactivity at the community level.

A low-cost and portable wrist exoskeleton using EEG-sEMG combined strategy for prolonged active rehabilitation.

Introduction: Hemiparesis is a common consequence of stroke that severely impacts the life quality of the patients. Active training is a key factor in achieving optimal neural recovery, but current systems for wrist rehabilitation present challenges in terms of portability, cost, and the potential for muscle fatigue during prolonged use. Methods: To address these challenges, this paper proposes a low-cost, portable wrist rehabilitation system with a control strategy that combines surface electromyogram (sEMG) and electroencephalogram (EEG) signals to encourage patients to engage in consecutive, spontaneous rehabilitation sessions. In addition, a detection method for muscle fatigue based on the Boruta algorithm and a post-processing layer are proposed, allowing for the switch between sEMG and EEG modes when muscle fatigue occurs. Results: This method significantly improves accuracy of fatigue detection from 4.90 to 10.49% for four distinct wrist motions, while the Boruta algorithm selects the most essential features and stabilizes the effects of post-processing. The paper also presents an alternative control mode that employs EEG signals to maintain active control, achieving an accuracy of approximately 80% in detecting motion intention. Discussion: For the occurrence of muscle fatigue during long term rehabilitation training, the proposed system presents a promising approach to addressing the limitations of existing wrist rehabilitation systems.

RNA methylation pattern and immune microenvironment characteristics mediated by m6A regulator in ischemic stroke.

Background: Ischemic stroke (IS) is a highly heterogeneous disease. Recent studies have shown that epigenetic variables affect the immune response. However, only a few studies have examined the relationship between IS and m6A immunoregulation. Therefore, we aim to explore the methylation of RNA mediated by m6A regulatory factor and the immune microenvironment characteristics of IS. Methods: Differentially expressed m6A regulators were detected in IS microarray datasets GSE22255 and GSE58294. We used a series of machine learning algorithms to identify key IS-related m6A regulators and validated them on blood samples of IS patients, oxygen-glucose deprivation/reoxygenation (OGD/R) microglia and GSE198710 independent data sets. Different m6A modification modes were determined and the patients were classified. In addition, we systematically associate these modification patterns with the characteristics of immune microenvironment, including infiltrating immune cells, immune function genes and immune response genes. Then we developed a model of m6A score to quantify the m6A modification in IS samples. Results: Through the analysis of the differences between the control group and IS patients, METTL16, LRPPRC, and RBM15 showed strong diagnostic significance in three independent data sets. In addition, qRT-PCR and Western blotting also confirmed that the expression of METTL16 and LRPPRC was downregulated and the expression of RBM15 was upregulated after ischemia. Two m6A modification modes and two m6A gene modification modes were also identified. m6A gene cluster A (high m6A value group) was positively correlated with acquired immunity, while m6A gene cluster B (low m6A value group) was positively correlated with innate immunity. Similarly, five immune-related hub genes were significantly associated with m6Acore (CD28, IFNG, LTF, LCN2, and MMP9). Conclusion: The modification of m6A is closely related to the immune microenvironment. The evaluation of individual m6A modification pattern may be helpful for future immunomodulatory therapy of anti-ischemic response.

A CNN-LSTM model for six human ankle movements classification on different loads.

This study aims to address three problems in current studies in decoding the ankle movement intention for robot-assisted bilateral rehabilitation using surface electromyogram (sEMG) signals: (1) only up to four ankle movements could be identified while six ankle movements should be classified to provide better training; (2) feeding the raw sEMG signals directly into the neural network leads to high computational cost; and (3) load variation has large influence on classification accuracy. To achieve this, a convolutional neural network (CNN)-long short-term memory (LSTM) model, a time-domain feature selection method of the sEMG, and a two-step method are proposed. For the first time, the Boruta algorithm is used to select time-domain features of sEMG. The selected features, rather than raw sEMG signals are fed into the CNN-LSTM model. Hence, the number of model's parameters is reduced from 331,938 to 155,042, by half. Experiments are conducted to validate the proposed method. The results show that our method could classify six ankle movements with relatively good accuracy (95.73%). The accuracy of CNN-LSTM, CNN, and LSTM models with sEMG features as input are all higher than that of corresponding models with raw sEMG as input. The overall accuracy is improved from 73.23% to 93.50% using our two-step method for identifying the ankle movements with different loads. Our proposed CNN-LSTM model have the highest accuracy for ankle movements classification compared with CNN, LSTM, and Support Vector Machine (SVM).

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.

Nanoarchitecture of a Two-Dimensional Few-Layer Graphene Oxide/π-Conjugated Polyimide Composite for Enhanced Photocatalytic Performance.

A novel two-dimensional graphene oxide/sulfur-doped polyimide (GO/SPI) hybrid polymer photocatalyst was synthesized by a facile ultrasonic chemical method. The characterization results showed that the skeleton structure of SPI was not changed when the few layers of GO were wrapped on the surface. Due to the excellent charge transport characteristics of GO and the strong π-π stacking interaction between two-dimensional GO and SPI, the photogenerated carrier transport capability of the GO/SPI composites was significantly enhanced compared with that of SPI. The efficient transmission and separation of photogenerated charge carriers significantly improve the photocatalytic degradation of the methyl orange activity of the GO/SPI composite. This work provides a facile and new way for the synthesis of metal-free inorganic-organic composite photocatalysts with high efficiency and low cost.

A general thermodynamics-triggered competitive growth model to guide the synthesis of two-dimensional nonlayered materials.

Two-dimensional (2D) nonlayered materials have recently provoked a surge of interest due to their abundant species and attractive properties with promising applications in catalysis, nanoelectronics, and spintronics. However, their 2D anisotropic growth still faces considerable challenges and lacks systematic theoretical guidance. Here, we propose a general thermodynamics-triggered competitive growth (TTCG) model providing a multivariate quantitative criterion to predict and guide 2D nonlayered materials growth. Based on this model, we design a universal hydrate-assisted chemical vapor deposition strategy for the controllable synthesis of various 2D nonlayered transition metal oxides. Four unique phases of iron oxides with distinct topological structures have also been selectively grown. More importantly, ultra-thin oxides display high-temperature magnetic ordering and large coercivity. MnxFeyCo3-x-yO4 alloy is also demonstrated to be a promising room-temperature magnetic semiconductor. Our work sheds light on the synthesis of 2D nonlayered materials and promotes their application for room-temperature spintronic devices.

The formation and structural characteristics of melanoidins from fermenting and distilled grains of Chinese liquor (baijiu).

Chinese liquor (baijiu) is a typical fermented food. In which production, melanoidins are formed in fermenting grains during low-temperature fermentation with long-term, and in distilled grains with high-temperature distillation for short-term. Here, the formation and structural characterization of melanoidins in these two distinct stages were first investigated through chemical composition analysis and spectroscopic identification. Our research showed that proteins and phenols continuously participate in melanoidin formation during fermentation and distillation processes. Distillation could produce melanoidins with larger amounts, darker colors, higher molecular weights, and more stable states than fermentation. The chemical composition including 10 carbohydrates, 17 amino acids, 5 free phenolic acids, and 7 bound phenolic acids was successfully identified in melanoidins. Ion chromatography was proposed to be an efficient method to investigate carbohydrates in melanoidins. Moreover, the potential impact of microorganisms on melanoidins was first revealed to be the possible utilization of glucose in melanoidins.

Investigation on the interaction between 1,3-dimethyltrisulfide and aroma-active compounds in sesame-flavor baijiu by Feller Additive Model, Odor Activity Value and Partition Coefficient.

The interaction between 1,3-dimethyltrisulfide and aroma-active compounds in sesame-flavor baijiu was evaluated by Feller's additive model and Odor Activity Value Approach, and the reason for the interaction can promote the release of fruity and caramel aromas of ethyl caproate, ethyl was explored by the Partition Coefficient Approach. The interaction results indicated that 1,3-dimethyltrisulfide caprate and furan-2-ylmethanol. Others showed masking effect. The Partition Coefficient showed that the effect of 1,3-dimethyltrisulfide on the volatility of esters was one of the reasons for the interaction affecting the flavor perception, and the volatility of ethyl esters with longer carbon chains at high phase ratio (PRs) is more likely to be promoted. Besides, the prediction model was initially proposed: y = 2.0112 ln(x) + 0.1461, which indicated that esters with the olfactory threshold lower than 33.80 µg/L are more likely to have positive effects with 1,3-dimethyltrisulfide, the negative effect is more likely to occur conversely.