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Spintronic devices based on antiferromagnetic (AFM) materials hold the promise of fast switching speeds and robustness against magnetic fields1–3. Different device concepts have been predicted4,5 and experimentally demonstrated, such as low-temperature AFM tunnel junctions that operate as spin-valves6, or room-temperature AFM memory, for which either thermal heating in combination with magnetic fields7 or Néel spin–orbit torque8 is used for the information writing process. On the other hand, piezoelectric materials were employed to control magnetism by electric fields in multiferroic heterostructures9–12, which suppresses Joule heating caused by switching currents and may enable low-energy-consuming electronic devices. Here, we combine the two material classes to explore changes in the resistance of the high-Néel-temperature antiferromagnet MnPt induced by piezoelectric strain. We find two non-volatile resistance states at room temperature and zero electric field that are stable in magnetic fields up to 60 T. Furthermore, the strain-induced resistance switching process is insensitive to magnetic fields. Integration in a tunnel junction can further amplify the electroresistance. The tunnelling anisotropic magnetoresistance reaches ~11.2% at room temperature. Overall, we demonstrate a piezoelectric, strain-controlled AFM memory that is fully operational in strong magnetic fields and has the potential for low-energy and high-density memory applications.

The anomalous Hall effect is a time-reversal symmetry-breaking magneto-electronic phenomenon originally discovered in ferromagnets. Recently, ruthenium dioxide (RuO 2 ) with a compensated antiparallel magnetic order has been predicted to generate an anomalous Hall effect of comparable strength to ferromagnets. The phenomenon arises from an altermagnetic phase of RuO 2 with a characteristic alternating spin polarization in both real-space crystal structure and momentum-space band structure. Here we report an anomalous Hall effect in RuO 2 with an anomalous Hall conductivity exceeding 1,000 Ω −1  cm −1 . We combine the vector magnetometry and magneto-transport measurements of epitaxial RuO 2 films of different crystallographic orientations. We show that the anomalous Hall effect dominates over an ordinary Hall contribution, and a contribution due to a weak field-induced magnetization. Our results could lead to the exploration of topological Berry phases and dissipationless quantum transport in crystals of abundant elements and with a compensated antiparallel magnetic order. By combining vector magnetometry and magneto-transport measurements of epitaxial films with different crystallographic orientations, an anomalous Hall effect can be measured in collinear altermagnetic ruthenium dioxide with an anomalous Hall conductivity exceeding 1,000 Ω –1  cm –1 .

Endangered species can achieve population growth through utilization. is an endangered species, which can be used in gardens and street trees. To avoid population degradation caused by long-term nursery cultivation, we need to introduce high-quality wild sources of germplasm for hybridization. In the past, when the selection of strains was carried out, attention was often paid to the performance of different traits of each strain. The strains with advantages in many more traits were selected as the target. In this paper, we proposed that excellent strains should be selected based on the needs of managers. We constructed a complex index composed of insect resistance and growth amount, which was concerned by plantation managers, for the selection of excellent strains. Its availability was confirmed as well. We cultivated 16 wild-sourced strains in a homogeneous garden and carried out experiments for 3 years. We measured 28 functional traits. Through collinearity diagnostics, 15 functional traits in 4 dimensions (morphology, leaf economy, stoichiometry and reproduction) were selected for analysis and construction of complex index. The influence of environmental factors on traits was excluded by comparing the trait matrix calculated based on Euclidean distance with the geographical distance matrix. Excellent strains (No. 15 from Dazeshan) selected based on the key complex index may not be outstanding in each trait, but have a more balanced performance among the trade-offs of trait combinations. We also explored the visualization of this key complex index by correlating with leaf carbon content (its ecologically relevant trait), so as to realize rapid and early selection of strains by using LCC (an easily measurable trait). To construct key complex index, appropriate functional traits should be selected according to the needs of managers or different species. The measurable traits with clear ecological links with complex index should be selected as \"agents\" to realize visualization of complex index.

Streptomycin-resistant (SM-resistant) Mycobacterium tuberculosis ( M . tuberculosis ) is a major concern in tuberculosis (TB) treatment. However, the mechanisms underlying streptomycin resistance remain unclear. This study primarily aimed to perform preliminary screening of genes associated with streptomycin resistance through conjoint analysis of multiple genomics. Genome-wide methylation, transcriptome, and proteome analyses were used to elucidate the associations between specific genes and streptomycin resistance in M . tuberculosis H37Rv. Methylation analysis revealed that 188 genes were differentially methylated between the SM-resistant and normal groups, with 89 and 99 genes being hypermethylated and hypomethylated, respectively. Furthermore, functional analysis revealed that these 188 differentially methylated genes were enriched in 74 pathways, with most of them being enriched in metabolic pathways. Transcriptome analysis revealed that 516 genes were differentially expressed between the drug-resistant and normal groups, with 263 and 253 genes being significantly upregulated and downregulated, respectively. KEGG analysis indicated that these 516 genes were enriched in 79 pathways, with most of them being enriched in histidine metabolism. The methylation level was negatively related to mRNA abundance. Proteome analysis revealed 56 differentially expressed proteins, including 14 upregulated and 42 downregulated proteins. Moreover, three hub genes ( coaE , fadE5 , and mprA ) were obtained using synthetic analysis. The findings of this study suggest that an integrated DNA methylation, transcriptome, and proteome analysis can provide important resources for epigenetic studies in SM-resistant M . tuberculosis H37Rv.

Background Cardiovascular diseases (CVDs) have the highest mortality worldwide. Human pluripotent stem cells (hPSCs) and their cardiomyocyte derivatives (hPSC-CMs) offer a valuable resource for disease modeling, pharmacological screening, and regenerative therapy. While most CVDs are linked to significant over-production of reactive oxygen species (ROS), the effects of current antioxidants targeting excessive ROS are limited. Nanotechnology is a powerful tool to develop antioxidants with improved selectivity, solubility, and bioavailability to prevent or treat various diseases related to oxidative stress. Cerium oxide nanozymes (CeONZs) can effectively scavenge excessive ROS by mimicking the activity of endogenous antioxidant enzymes. This study aimed to assess the nanotoxicity of CeONZs and their potential antioxidant benefits in stressed human embryonic stem cells (hESCs) and their derived cardiomyocytes (hESC-CMs). Results CeONZs demonstrated reliable nanosafety and biocompatibility in hESCs and hESC-CMs within a broad range of concentrations. CeONZs exhibited protective effects on the cell viability of hESCs and hESC-CMs by alleviating excessive ROS-induced oxidative stress. Moreover, CeONZs protected hESC-CMs from doxorubicin (DOX)-induced cardiotoxicity and partially ameliorated the insults from DOX in neonatal rat cardiomyocytes (NRCMs). Furthermore, during hESCs culture, CeONZs were found to reduce ROS, decrease apoptosis, and enhance cell survival without affecting their self-renewal and differentiation potential. Conclusions CeONZs displayed good safety and biocompatibility, as well as enhanced the cell viability of hESCs and hESC-CMs by shielding them from oxidative damage. These promising results suggest that CeONZs may be crucial, as a safe nanoantioxidant, to potentially improve the therapeutic efficacy of CVDs and be incorporated into regenerative medicine. Graphical Abstract

Background Transcription factors HAND1 and HAND2 (HAND1/2) play significant roles in cardiac organogenesis. Abnormal expression and deficiency of HAND1 / 2 result in severe cardiac defects. However, the function and mechanism of HAND1 / 2 in regulating human early cardiac lineage commitment and differentiation are still unclear. Methods With NKX2.5 eGFP H9 human embryonic stem cells (hESCs), we established single and double knockout cell lines for HAND1 and HAND2 , respectively, whose cardiomyocyte differentiation efficiency could be monitored by assessing NKX2.5-eGFP + cells with flow cytometry. The expression of specific markers for heart fields and cardiomyocyte subtypes was examined by quantitative PCR, western blot and immunofluorescence staining. Microelectrode array and whole-cell patch clamp were performed to determine the electrophysiological characteristics of differentiated cardiomyocytes. The transcriptomic changes of HAND knockout cells were revealed by RNA sequencing. The HAND1/2 target genes were identified and validated experimentally by integrating with HAND1/2 chromatin immunoprecipitation sequencing data. Results Either HAND1 or HAND2 knockout did not affect the cardiomyocyte differentiation kinetics, whereas depletion of HAND1 / 2 resulted in delayed differentiation onset. HAND1 knockout biased cardiac mesoderm toward second heart field progenitors at the expense of first heart field progenitors, leading to increased expression of atrial and outflow tract cardiomyocyte markers, which was further confirmed by the appearance of atrial-like action potentials. By contrast, HAND2 knockout cardiomyocytes had reduced expression of atrial cardiomyocyte markers and displayed ventricular-like action potentials. HAND1 / 2 -deficient hESCs were more inclined to second heart field lineage and its derived cardiomyocytes with atrial-like action potentials than HAND1 single knockout during differentiation. Further mechanistic investigations suggested TBX5 as one of the downstream targets of HAND1/2, whose overexpression partially restored the abnormal cardiomyocyte differentiation in HAND1 / 2 -deficient hESCs. Conclusions HAND1 / 2 have specific and redundant roles in cardiac lineage commitment and differentiation. These findings not only reveal the essential function of HAND1/2 in cardiac organogenesis, but also provide important information on the pathogenesis of HAND1 / 2 deficiency-related congenital heart diseases, which could potentially lead to new therapeutic strategies.

The WHO’s “Global tuberculosis report 2020” lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 10 8 ) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo , regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy.

The spalt ( Sal ) gene family has four members ( Sall1-4 ) in vertebrates, all of which play pivotal roles in various biological processes and diseases. However, the expression and function of SALL2 in development are still less clear. Here, we first charted SALL2 protein expression pattern during mouse embryo development by immunofluorescence, which revealed its dominant expression in the developing nervous system. With the establishment of Sall2 deficient mouse embryonic stem cells (ESCs), the in vitro neural differentiation system was leveraged to interrogate the function of SALL2, which showed impaired neural differentiation of Sall2 knockout (KO) ESCs. Furthermore, neural stem cells (NSCs) could not be derived from Sall2 KO ESCs and the generation of neural tube organoids (NTOs) was greatly inhibited in the absence of SALL2. Meanwhile, transgenic expression of E1 isoform of SALL2 restored the defects of neural differentiation in Sall2 KO ESCs. By chromatin immunoprecipitation sequencing (ChIP-seq), Tuba1a was identified as downstream target of SALL2, whose function in neural differentiation was confirmed by rescuing neural phenotypes of Sall2 KO ESCs when overexpressed. In sum, by elucidating SALL2 expression dynamics during early mouse development and mechanistically characterizing its indispensable role in neural differentiation, this study offers insights into SALL2’s function in human nervous system development, associated pathologies stemming from its mutations and relevant therapeutic strategy.

Cardiac biological pacing (BP) is one of the future directions for bradyarrhythmias intervention. Currently, cardiac pacemaker cells (PCs) used for cardiac BP are mainly derived from pluripotent stem cells (PSCs). However, the production of high-quality cardiac PCs from PSCs remains a challenge. Here, we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of PCs. First, two PC markers, Shox2 and Hcn4 , were selected to establish Shox2:EGFP; Hcn4:mCherry mouse PSC reporter line. Then, by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation, we designed the FSK method that increased the yield of SHOX2 + ; HCN4 + cells with typical PC characteristics, which was 12 and 42 folds higher than that of the embryoid body (EB) and the monolayer M10 methods respectively. In addition, the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing (scRNA-seq), which resembled in vivo PCs development, and ZFP503 was verified as a key regulator of cardiac PCs differentiation. These PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology, help with the understanding of PCs (patho)physiology, and benefit drug discovery for PC-related diseases as well.

Tuberculosis (TB) is one of the most serious infectious diseases globally and has high mortality rates. A variety of diagnostic tests are available, yet none are wholly reliable. Serum cytokines, although significantly and frequently induced by different diseases and thus good biomarkers for disease diagnosis and prognosis, are not sufficiently disease-specific. TB-specific antibody detection, on the other hand, has been reported to be highly specific but not sufficiently sensitive. In this study, our aim was to improve the sensitivity and specificity of TB diagnosis by combining detection of TB-related cytokines and TB-specific antibodies in peripheral blood samples. TB-related serum cytokines were screened using a human cytokine array. TB-related cytokines and TB-specific antibodies were detected in parallel with microarray technology. The diagnostic performance of the new protocol for active TB was systematically compared with other traditional methods. Here, we show that cytokines I-309, IL-8 and MIG are capable of distinguishing patients with active TB from healthy controls, patients with latent TB infection, and those with a range of other pulmonary diseases, and that these cytokines, and their presence alongside antibodies for TB-specific antigens Ag14-16kDa, Ag32kDa, Ag38kDa and Ag85B, are specific markers for active TB. The diagnostic protocol for active TB developed here, which combines the detection of three TB-related cytokines and TB-specific antibodies, is highly sensitive (91.03%), specific (90.77%) and accurate (90.87%). Our results show that combining detection of TB-related cytokines and TB-specific antibodies significantly enhances diagnostic accuracy for active TB, providing greater accuracy than conventional diagnostic methods such as interferon gamma release assays (IGRAs), TB antibody Colloidal Gold Assays and microbiological culture, and suggest that this diagnostic protocol has potential for clinical application.