Approaching crystal's limit of thermoelectrics by nano-sintering-aid at grain boundaries.

Grain boundary plays a vital role in thermoelectric transports, leading to distinct properties between single crystals and polycrystals. Manipulating the grain boundary to realize good thermoelectric properties in polycrystals similar as those of single crystals is a long-standing task, but it is quite challenging. Herein, we develop a liquid-phase sintering strategy to successfully introduce Mg2Cu nano-sintering-aid into the grain boundaries of Mg3(Bi, Sb)2-based materials. The nano-aid helps to enlarge the average grain size to 23.7 µm and effectively scatter phonons, leading to excellent electrical transports similar as those of single crystals and ultralow lattice thermal conductivity as well as exceptional thermoelectric figure of merit (1.5 at 500 K) and conversion efficiency (7.4% under temperature difference of 207 K). This work provides a simple but effective strategy for the fabrication of high-performance polycrystals for large-scale applications.

Contribution of ferroptosis and SLC7A11 to light-induced photoreceptor degeneration.

Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss. Ferroptosis has been demonstrated to be associated with retinal degenerative diseases. However, the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored. Bioinformatics and biochemical analyses in this study revealed xC-, solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model. This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway, through which cystine depletion, iron ion accumulation, and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment. We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo. Conversely, solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H2O2-induced ferroptosis of 661W cells. These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.

Influences of thioalcohols on the release of aromas in sesame-flavor baijiu.

This study investigated the interactions between 2-furylmethanethiol, benzenemethanethiol, and 18 skeletal aroma-active compounds as well as four aroma notes in sesame-flavor baijiu based on the Feller Additive Model, the Odor Activity Value (OAV) Approach, and the Sigma-Tau (σ-τ) plots. In addition, a predictive model for the interactions between 2-furylmethanethiol and esters was developed, and the determinants of the interaction results in complex systems were explored. The results reveal that both thioalcohols interacted with the skeletal aroma-active compounds in a similar trend, where 2-furylmethanethiol tends to enhance the release of fruit and acid aroma. Moreover, the intensity of the thiols and their intensity ratio to the notes were the determinants of the interaction results in the multivariate blended system, with the lower the concentration of the thiols, the closer the ratio was to 1, and the more likely that additive interactions would take place. Predictive modeling showed that 2-furylmethanethiols were more likely to have additive or synergistic effects with esters when the olfactory thresholds of the esters were between 75.86 and 199.53 µg/L. Conversely, masking effects were more likely.

Porous Organic Cage as an Efficient Platform for Industrial Radioactive Iodine Capture.

Herein, we firstly develop porous organic cage (POC) as an efficient platform for highly effective radioactive iodine capture under industrial operating conditions (typically ≥ 150 °C, ≤ 150 ppmv of I2). Due to the highly dispersed and readily accessible binding sites as well as sufficient accommodating space, the constructed NKPOC-DT-(I-)Me (NKPOC = Nankai porous organic cage) demonstrates a record-high I2 uptake capacity of 48.35 wt% and extraordinary adsorption capacity of unit ionic site (~1.62) at 150 °C and 150 ppmv of I2. The I2 capacity is 3.5, 1.6, and 1.3 times higher than industrial silver-based adsorbents Ag@MOR and benchmark materials of TGDM and 4F-iCOF-TpBpy-I- under the same conditions. Furthermore, NKPOC-DT-(I-)Me exhibits remarkable adsorption kinetics (k1 = 0.013 min-1), which is 1.2 and 1.6 times higher than TGDM and 4F-iCOF-TpBpy-I- under the identical conditions. NKPOC-DT-(I-)Me thus sets a new benchmark for industrial radioactive I2 adsorbents. This work not only provides a new insight for effectively enhancing the adsorption capacity of unit functional sites, but also advances POC as an efficient platform for radioiodine capture in industry.

Ductile P-Type AgCu(Se,S,Te) Thermoelectric Materials.

Ductile inorganic thermoelectric (TE) materials open a new approach to develop high-performance flexible TE devices. N-type Ag2(S,Se,Te) and p-type AgCu(Se,S,Te) pseudoternary solid solutions are two typical categories of ductile inorganic TE materials reported so far. Comparing with the Ag2(S,Se,Te) pseudoternary solid solutions, the phase composition, crystal structure, and physical properties of AgCu(Se,S,Te) pseudoternary solid solutions are more complex, but their relationships are still ambiguous now. In this work, via systematically investigating the phase composition, crystal structure, mechanical, and TE properties of about 60 AgCu(Se,S,Te) pseudoternary solid solutions, the comprehensive composition-structure-property phase diagrams of the AgCuSe-AgCuS-AgCuTe pseudoternary system is constructed. By mapping the complex phases, the "ductile-brittle" and "n-p" transition boundaries are determined and the composition ranges with high TE performance and inherent ductility are illustrated. On this basis, high performance p-type ductile TE materials are obtained, with a maximum zT of 0.81 at 340 K. Finally, flexible in-plane TE devices are prepared by using the AgCu(Se,S,Te)-based ductile TE materials, showing high output performance that is superior to those of organic and inorganic-organic hybrid flexible devices.

Assessing immune hepatotoxicity of troglitazone with a versatile liver-immune-microphysiological-system.

Drug-induced liver injury is a prevalent adverse event associated with pharmaceutical agents. More significantly, there are certain drugs that present severe hepatotoxicity only during the clinical phase, consequently leading to the termination of drug development during clinical trials or the withdrawal from the market after approval. The establishment of an evaluation model that can sensitively manifest such hepatotoxicity has always been a challenging aspect in drug development. In this study, we build a liver-immune-microphysiological-system (LIMPS) to fully demonstrate the liver injury triggered by troglitazone (TGZ), a drug that was withdrawn from the market due to hepatotoxicity. Leveraging the capabilities of organ-on-chip technology allows for the dynamic modulation of cellular immune milieu, as well as the synergistic effects between drugs, hepatocytes and multiple immune cells. Through the LIMPS, we discovered that 1) TGZ can promote neutrophils to adhered hepatocytes, 2) the presence of TGZ enhances the crosstalk between macrophages and neutrophils, 3) the induction of damage in hepatocytes by TGZ at clinically relevant blood concentrations not observed in other in vitro experiments, 4) no hepatotoxicity was observed in LIMPS when exposed to rosiglitazone and pioglitazone, structurally similar analogs of TGZ, even at the higher multiples of blood drug concentration levels. As an immune-mediated liver toxicity assessment method, LIMPS is simple to operate and can be used to test multiple drug candidates to detect whether they will cause severe liver toxicity in clinical settings as early as possible.

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.

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.

Lama1 upregulation prolongs the lifespan of the dyH/dyH mouse model of LAMA2-related congenital muscular dystrophy.

LAMA2-related congenital muscular dystrophy (LAMA2-CMD), characterized by laminin-α2 deficiency, is debilitating and ultimately fatal. To date, no effective therapy has been clinically available. Laminin-α1, which shares significant similarities with laminin-α2, has been proven as a viable compensatory modifier. To evaluate its clinical applicability, we establish a Lama2 exon-3 deletion mouse model (dyH/dyH). The dyH/dyH mice exhibit early lethality and typical LAMA2-CMD phenotypes, allowing the evaluation of various endpoints. In dyH/dyH mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation, a nearly doubled median survival is observed, as well as improvements in weight and grip. Significant therapeutical effects are revealed by MRI, serum biochemical indices, and muscle pathology studies. Treating LAMA2-CMD with LAMA1 upregulation is feasible and that early intervention can alleviate symptoms and extend lifespan. Additionally, we reveal limitations of LAMA1 upregulation, including high-dose mortality and non-sustained expression, which require further optimization in future studies.

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.