Artemisinin and salinomycin co-loaded nanozymes to boost cascade ROS accumulation for augmented tumor ferroptosis.

Ferroptosis, which depends on iron ions to generate reactive oxygen species (ROS), has been proved to be an effective strategy for cancer therapy. However, cells will initiate different programs, including reducing iron uptake and storing excess iron in ferritin, to lower the intracellular iron concentration. In this work, we reported a simple, one-pot method to synthesize bovine serum albumin stabilized MnFe2O4 nanoparticles (MnFe2O4@BSA NPs) for ferroptosis therapy of cancer. Artemisinin (ART) and salinomycin (Sali), which could induce the degradation of ferritin and enhance the uptake by increasing binding protein IRP2 and transferrin receptor, were loaded onto the MnFe2O4@BSA NPs to strengthen the killing effect. The prepared MnFe2O4@BSA-ART/Sali (MnFe2O4/ART/Sali) NPs could significantly increase the cellular iron concertation, enhancing the ROS generation in cells. After intravenous injection, the MnFe2O4/ART/Sali NPs showed superior anti-tumor effects, with a tumor inhibition rate of 67.65 %. Hence, the hybrid nanocomposite indicated the combined effect of MnFe2O4, ART, and Sali, providing a platform to enhance ferroptosis therapy of cancer.

Corrigendum: Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.

[This corrects the article DOI: 10.3389/fimmu.2024.1309447.].

Single-cell transcriptomics reveals tumor microenvironment changes and prognostic gene signatures in hepatocellular carcinoma.

BACKGROUND: Hepatocellular Carcinoma (HCC) is the most common type of primary liver cancer, accounting for the majority of liver cancer cases. Hepatocellular Carcinoma not only exhibits high heterogeneity but also possesses an immune-suppressive tumor microenvironment that promotes tumor evasion, posing substantial difficulties for efficient therapy. Our aim is to utilize single-cell RNA transcriptome data to investigate the dynamic changes in the tumor microenvironment during the malignant progression of HCC, the communication among immune cells, and the marker genes associated with patient prognosis. METHODS: We constructed expression matrices from open single-cell RNA transcriptome data (GSE149614) of HCC patients (representing stages I-IV), establishing single-cell RNA transcriptional atlases for different stages of HCC progression. For each stage, we conducted cell subgroup analysis to identify cell types at each stage. Horizontally, we explored the dynamic changes of the same cell type across different stages, performing trajectory analysis and prognosis analysis. Vertically, we investigated pairwise comparisons of different stages of HCC progression, probing the dynamic alterations in tumor microenvironment immune cell signaling pathways. Finally, potential drugs for the treatment of HCC were predicted based on relevant genes. FINDINGS: As the HCC advances towards increased malignancy, there is a shift in the predominant composition of the tumor microenvironment, with a decline in the dominance of hepatic cells. Tumor-infiltrating immune cells migrate and accumulate within the tumor microenvironment, where T cells and myeloid cells display distinct patterns of change. Genes associated with cancer-associated fibroblasts (CAFs) and T cells are correlated with adverse patient outcomes. In the late stages of HCC, the tumor microenvironment is infiltrated by more myeloid-derived suppressor cells (MDSCs), and a prognostic model constructed based on genes related to myeloid cells can predict patient outcomes. Additionally, in the analysis of transcription factors, YY1 and MYC are found to be highly expressed. Cell communication analysis among tumor-infiltrating immune cells reveals significant differences in the main signaling pathways at different stages of HCC progression. Finally, drug sensitivity analysis based on key genes identifies Acetalax, Allopurinol, and Amonafide as potential candidates for HCC treatment.

Tissue distribution, biomagnification, human health risk, and risk mitigation of perfluoroalkyl acids (PFAAs) in the aquatic food web of an urban fringe lake: Insights from urban-rural and seasonal scales.

Perfluoroalkyl acids (PFAAs), renowned for their exceptional physical and chemical properties, are ubiquitous in urban and rural environments. Despite their widespread usage, more knowledge is needed concerning their accumulation and transfer mechanisms within the aquatic food webs of urban fringe lakes, especially across rural-urban and seasonal scales. This study investigated the tissue distribution, bioaccumulation, biomagnification, associated human health risks, and potential risk mitigation strategies of 15 PFAAs within the food web of Luoma Lake, a prototypical urban fringe lake. All targeted PFAAs were detected in samples, with ∑PFAA concentrations ranging from 116.97 to 564.26 ng/g dw in muscles and 26.96-1850.95 ng/g dw in viscera. Spatial variations revealed significantly higher ∑PFAA concentrations in the muscles from the urban subregion (∑PFAA: 359.66 ± 76.48 ng/g dw) compared to the rural subregion (∑PFAA: 328.86 ± 87.51 ng/g dw). Seasonal fluctuations impacted PFAA concentrations in fish and crustacean muscles but exhibited negligible effects on bivalve muscles. Spatial variations only influenced PFAA concentrations in specific viscera (gill, liver, kidney), while seasonal changes had minimal effects on viscera. The organisms demonstrated varying bioaccumulation capacities, with crustaceans displaying the highest bioaccumulation potential, followed by crustaceans and fish. Both spatial and seasonal variations modulated the bioaccumulation patterns of PFAA in muscles, whereas bioaccumulation in viscera was only influenced by seasonal factors. Notably, PFAA biomagnification along the food web was exclusively governed by spatial distribution, remaining unaffected by seasonal changes. The human health risk assessment underscored the potential adverse health impacts of PFOS and PFOA, particularly on young children (aged 2 to <6 years). This study further proposed comprehensive recommendations for mitigating PFAA-induced health risks, encompassing source control, selective consumption, pre-cooking treatments, and strategic cooking method selection. This research provides crucial insights into the ecological behaviors and health implications of PFAA in urban fringe lakes.

Distinct Olfactory Bulb-Cortex Neural Circuits Coordinate Cognitive Function in Parkinson's Disease.

Cognitive dysfunction stands as a prevalent and consequential non-motor manifestation in Parkinson's disease (PD). Although dysfunction of the olfactory system has been recognized as an important predictor of cognitive decline, the exact mechanism by which aberrant olfactory circuits contribute to cognitive dysfunction in PD is unclear. Here, we provide the first evidence for abnormal functional connectivity across olfactory bulb (OB) and piriform cortex (PC) or entorhinal cortex (EC) by clinical fMRI, and dysfunction of neural coherence in the olfactory system in PD mice. Moreover, we discovered that 2 subpopulations of mitral/tufted (M/T) cells in OB projecting to anterior PC (aPC) and EC precisely mediated the process of cognitive memory respectively by neural coherence at specific frequencies in mice. In addition, the transcriptomic profiling analysis and functional genetic regulation analysis further revealed that biorientation defective 1 (Bod1) may play a pivotal role in encoding OBM/T-mediated cognitive function. We also verified that a new deep brain stimulation protocol in OB ameliorated the cognitive function of Bod1-deficient mice and PD mice. Together, aberrant coherent activity in the olfactory system can serve as a biomarker for assessing cognitive function and provide a candidate therapeutic target for the treatment of PD.

Evaluation of a Quadrivalent Shigella flexneri Serotype 2a, 3a, 6, and Shigella sonnei O-Specific Polysaccharide and IpaB MAPS Vaccine.

BACKGROUND: Shigellosis is the leading cause of diarrheal deaths worldwide and is particularly dangerous in children under 5 years of age in low- and middle-income countries. Additionally, the rise in antibiotic resistance has highlighted the need for an effective Shigella vaccine. Previously, we have used the Multiple Antigen-Presenting System (MAPS) technology to generate monovalent and quadrivalent Salmonella MAPS vaccines that induce functional antibodies against Salmonella components. METHODS: In this work, we detail the development of several monovalent vaccines using O-specific polysaccharides (OSPs) from four dominant serotypes, S. flexneri 2a, 3a, and 6, and S. sonnei. We tested several rhizavidin (rhavi) fusion proteins and selected a Shigella-specific protein IpaB. Quadrivalent MAPS were made with Rhavi-IpaB protein and tested in rabbits for immunogenicity. RESULTS: Individual MAPS vaccines generated robust, functional antibody responses against both IpaB and the individual OSP component. Antibodies to IpaB were effective across Shigella serotypes. We also demonstrate that the OSP antibodies generated are specific to each homologous Shigella O type by performing ELISA and bactericidal assays. We combined the components of each MAPS vaccine to formulate a quadrivalent MAPS vaccine which elicited similar antibody and bactericidal responses compared to their monovalent counterparts. Finally, we show that the quadrivalent MAPS immune sera are functional against several clinical isolates of the serotypes used in the vaccine. CONCLUSIONS: This quadrivalent MAPS Shigella vaccine is immunogenicity and warrants further study.

Efficacy of haploidentical allogeneic hematopoietic cell transplantation following two courses of venetoclax and azacytidine therapy in patients over 55 years old with acute myelogenous leukemia.

INTRODUCTION: The combination of venetoclax (VEN) and azacytidine (AZA) has demonstrated potential in achieving rapid and effective remissions in elderly patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation is a promising potential cure for high-risk AML, as VEN-based therapies have a worse prognosis in elderly patients. This study aimed to assess the efficacy of sequential haploidentical HSCT following two courses of VEN and AZA therapy in patients with AML aged 55 years and older. METHODS: We conducted a retrospective study on AML patients aged 55 to 70 years who received intensive chemotherapy or two courses of VEN/AZA therapy, followed by haplo-HSCT based on disease risk degree, measurable residual disease status and patient's preference. RESULTS: Between January 2019 and December 2023, 141 newly diagnosed AML patients received initial treatment with intensive chemotherapy or VEN/AZA therapy. Among them, 64 patients received haplo-HSCT, while 77 did not. The 1-year over survival (OS) and relapse-free survival (RFS) of patients who received haplo-HSCT were significantly higher than those who did not receive haplo-HSCT (P<0.05). Among patients who received transplantation, there was no significant difference in 1-year OS and RFS between the VEN/AZA and intensive chemotherapy groups: 76.3% vs 69.3% (P = 0.367) for OS, and 74.5% vs 69.7% (P = 0.473) for RFS. High-risk ELN stratification and the presence of ≥4 gene mutations were associated with lower OS and RFS in both univariate and multivariate analysis. CONCLUSIONS: AML patients over 55 years of age who received haplo-HSCT after two courses of VEN/AZA therapy had outcomes similar to those who received haplo-HSCT after intensive chemotherapy, suggesting that two courses of VEN/AZA therapy as a bridge to halpo-HSCT are feasible for patients over 55 years old.

Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.

Lupus nephritis (LN), a complex complication of systemic lupus erythematosus, requires in-depth cellular and molecular analysis for advanced treatment strategies, including mRNA vaccine development. In this study, we analyzed single-cell RNA sequencing data from 24 LN patients and 10 healthy controls, supplemented by bulk RNA-seq data from additional LN patients and controls. By applying non-negative matrix factorization (NMF), we identified four distinct leukocyte meta-programs in LN, highlighting diverse immune functions and potential mRNA vaccine targets. Utilizing 12 machine learning algorithms, we developed 417 predictive models incorporating gene sets linked to key biological pathways, such as MTOR signaling, autophagy, Toll-like receptor, and adaptive immunity pathways. These models were instrumental in identifying potential targets for mRNA vaccine development. Our functional network analysis further revealed intricate gene interactions, providing novel insights into the molecular basis of LN. Additionally, we validated the mRNA expression levels of potential vaccine targets across multiple cohorts and correlated them with clinical parameters such as the glomerular filtration rate (GFR) and pathological stage. This study represents a significant advance in LN research by merging single-cell genomics with the precision of NMF and machine learning, broadening our understanding of LN at the cellular and molecular levels. More importantly, our findings shed light on the development of targeted mRNA vaccines, offering new possibilities for diagnostics and therapeutics for this complex autoimmune disease.

A novel mutation of LYST and haemophagocytic lymphohistiocytosis as the first symptom in children with ph+ALL: A case report and literature review.

Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder. This study sheds light on a rare and intriguing case of HLH as the initial symptom in a child with Philadelphia chromosome-positive acute lymphoblastic leukaemia (ph+ALL). This case report, accompanied by a comprehensive literature review, highlights the diagnostic challenges and treatment complexities encountered in the management of such rare manifestations. Moreover, the identification of a novel mutation in the LYST gene adds a unique genetic perspective to the understanding of HLH pathogenesis, potentially opening avenues for further research in this area.

A qualitative study of patient competence for patient engagement in their safety--from the perspective of nurses and patients.

OBJECTIVES: To describe the essential competencies required for patient engagement in their own safety. METHOD: We adopted a phenomenological approach in qualitative research to conduct semi-structured interviews with nurses (n = 14) and adult patients (n = 13) from different departments. By deeply exploring their experiences and feelings about patient engagement in patient safety, we sought to understand their views on the qualities that patients need to possess in order to participate in their own safety. RESULTS: From the interviews, we identified six major themes, including competence of information sharing, competence of taking patient engagement as responsibility and right, competence of making equal communication, competence of maintaining trust relationship with health personnels, competence of accepting non-punitive safety culture, need of resource support, five of them showed essential competences for patients and one of them showed patients' need for promoting their engagement. CONCLUSION: The findings of this study show necessary competence and needs in patient engagement process of patient, offer a foundational reference for constructing a measurement tool for patient engagement in patient safety competence in the future, so that medical staff and patients can provide reference for the future targeted construction of patient competence improvement programs. At the same time, improving patient competence and engagement to better achieve safety goals requires the joint efforts of patients, medical staff, medical institutions, the government, and society.

Nomograms to predict occult contralateral central lymph node metastases in unilateral papillary thyroid carcinoma with ipsilateral clinical lymph node metastasis.

BACKGROUND: No significant difference in disease-specific survival and recurrence-free survival exists between papillary thyroid cancer (PTC) patients with high-risk features subjected to lobectomy and thyroidectomy. However, it is unclear which type of patients with unilateral PTC combined with ipsilateral clinical involved lymph nodes (cN1) can receive a less aggressive treatment. METHODS: We collected the medical records of 631 patients diagnosed with unilateral PTC and ipsilateral cN1. These patients initially underwent total thyroidectomy and bilateral central lymph node dissection (LND), with or without lateral LND. We conducted an analysis to investigate the associations between contralateral occult central lymph node metastasis (CLNM) and clinicopathologic factors. RESULTS: The proportion of contralateral occult CLNM was 38.9 %. Age ≤45 years, tumor diameter >1 cm, obesity, and involvement of lymph node regions ≥2 were independent risk factors for contralateral occult CLNM. Multifocality and ipsilateral neck high-volume lymph node metastases were independent risk factors among the postoperative pathological factors. A predicting model was developed to quantify the risk of each factor, which revealed that patients without any of the risk factors mentioned above had a 20-30 % probability of contralateral occult CLNM, whereas the probability was greater than 60 % when all factors were present. CONCLUSION: Based on the predictive nomograms, we proposed a risk stratification scheme based on different nomogram scores. In the debate about prophylactic central LND among contralateral central lymph node in unilateral PTC with ipsilateral clinical LNM, our nomograms provide the balance to avoid overtreatment and undertreatment through personal risk assessment.

Phase II study of novel CXCR2 agonist and Plerixafor for rapid stem cell mobilization in patients with multiple myeloma.

MGTA-145 or GROßT, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical studies and healthy volunteers. Twenty-five patients with multiple myeloma enrolled in a phase 2 trial evaluating MGTA-145 and plerixafor for HSC mobilization (NCT04552743). Plerixafor was given subcutaneously followed 2 h later by MGTA-145 (0.03 mg/kg) intravenously with same day apheresis. Mobilization/apheresis could be repeated for a second day in patients who collected <6 ×106 CD34+ cells/kg. Lenalidomide and anti-CD38 antibody were part of induction therapy in 92% (n = 23) and 24% (n = 6) of patients, respectively. Median total HSC cell yield (CD34+ cells/kg × 106) was 5.0 (range: 1.1-16.2) and day 1 yield was 3.4 (range: 0.3-16.2). 88% (n = 22) of patients met the primary endpoint of collecting 2 ×106 CD34+ cells/kg in ≤ two days, 68% (n = 17) in one day. Secondary endpoints of collecting 4 and 6 × 106 CD34+ cells/kg in ≤ two days were met in 68% (n = 17) and 40% (n = 10) patients. Grade 1 or 2 adverse events (AE) were seen in 60% of patients, the most common AE being grade 1 pain, usually self-limited. All 19 patients who underwent transplant with MGTA-145 and plerixafor mobilized HSCs engrafted successfully, with durable engraftment at day 100. 74% (17 of 23) of grafts with this regimen were minimal residual disease negative by next generation flow cytometry. Graft composition for HSCs and immune cells were similar to a contemporaneous cohort mobilized with G-CSF and plerixafor.

Hydrogen peroxide participates in leaf senescence by inhibiting CHLI1 activity.

KEY MESSAGE: Hydrogen peroxide promoted leaf senescence by sulfenylating the magnesium chelating protease I subunit (CHLI1) in the chlorophyll synthesis pathway, and inhibited its activity to reduce chlorophyll synthesis. Leaf senescence is the final and crucial stage of plant growth and development, during which chlorophyll experiences varying degrees of destruction. It is well-known that the higher ROS accumulation is a key factor for leaf senescence, but whether and how ROS regulates chlorophyll synthesis in the process are unknown. Here, we report that H2O2 inhibits chlorophyll synthesis during leaf senescence via the I subunit of magnesium-chelatase (CHLI1). During leaf senescence, the decrease of chlorophyll content is accompanied by the increase of H2O2 accumulation, as well as the inhibition of catalase (CAT) genes expression. The mutant cat2-1, with increased H2O2 shows an accelerated senescence phenotype and decreased CHLI1 activity compared with the wild type. H2O2 inhibits CHLI1 activity by sulfenylating CHLI1 during leaf senescence. Consistent with this, the chli1 knockout mutant displays the same premature leaf senescence symptom as cat2-1, while overexpression of CHLI1 in cat2-1 can partially restore its early senescence phenotype. Taken together, these results illustrate that CAT2-mediated H2O2 accumulation during leaf senescence represses chlorophyll synthesis through sulfenylating CHLI1, and thus inhibits its activity, providing a new insight into the pivotal role of chlorophyll synthesis as a participant in orchestrating the leaf senescence.

On approximate equality of Z-values of the statistical tests for win statistics (win ratio, win odds, and net benefit).

Dong et al. (2023) showed that the win statistics (win ratio, win odds, and net benefit) can complement each another to demonstrate the strength of treatment effects in randomized trials with prioritized multiple outcomes. This result was built on the connections among the point and variance estimates of the three statistics, and the approximate equality of Z-values in their statistical tests. However, the impact of this approximation was not clear. This Discussion refines this approach and shows that the approximate equality of Z-values for the win statistics holds more generally. Thus, the three win statistics consistently yield closely similar p-values. In addition, our simulations show an example that the naive approach without adjustment for censoring bias may produce a completely opposite conclusion from the true results, whereas the IPCW (inverse-probability-of-censoring weighting) approach can effectively adjust the win statistics to the corresponding true values (i.e. IPCW-adjusted win statistics are unbiased estimators of treatment effect).

A fair individualized polysocial risk score for identifying increased social risk in type 2 diabetes.

Racial and ethnic minorities bear a disproportionate burden of type 2 diabetes (T2D) and its complications, with social determinants of health (SDoH) recognized as key drivers of these disparities. Implementing efficient and effective social needs management strategies is crucial. We propose a machine learning analytic pipeline to calculate the individualized polysocial risk score (iPsRS), which can identify T2D patients at high social risk for hospitalization, incorporating explainable AI techniques and algorithmic fairness optimization. We use electronic health records (EHR) data from T2D patients in the University of Florida Health Integrated Data Repository, incorporating both contextual SDoH (e.g., neighborhood deprivation) and person-level SDoH (e.g., housing instability). After fairness optimization across racial and ethnic groups, the iPsRS achieved a C statistic of 0.71 in predicting 1-year hospitalization. Our iPsRS can fairly and accurately screen patients with T2D who are at increased social risk for hospitalization.

Self-limiting multimerization of α-synuclein on membrane and its implication in Parkinson's diseases.

α-Synuclein (α-syn), a crucial molecule in Parkinson's disease (PD), is known for its interaction with lipid membranes, which facilitates vesicle trafficking and modulates its pathological aggregation. Deciphering the complexity of the membrane-binding behavior of α-syn is crucial to understand its functions and the pathology of PD. Here, we used single-molecule imaging to show that α-syn forms multimers on lipid membranes with huge intermultimer distances. The multimers are characterized by self-limiting growth, manifesting in concentration-dependent exchanges of monomers, which are fast at micromolar concentrations and almost stop at nanomolar concentrations. We further uncovered movement patterns of α-syn's occasional trapping on membranes, which may be attributed to sparse lipid packing defects. Mutations such as E46K and E35K may disrupt the limit on the growth, resulting in larger multimers and accelerated amyloid fibril formation. This work emphasizes sophisticated regulation of α-syn multimerization on membranes as a critical underlying factor in the PD pathology.

IFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway.

Type I interferon (IFN-I) and its downstream genes play a profound role in HIV infection. In this study, we found that an IFN-inducible gene, IFI27, was upregulated in HIV-1 infection, which in turn efficiently suppressed HIV-1 replication, specially degraded the viral gag protein, including p24 and p55 subunits. Notably, the anti-HIV-1 activity of IFI27 in Old World monkeys surpassed that in New World monkeys, and IFI27 has a higher potentially inhibitory effect on HIV-1 than simian immunodeficiency virus (SIV). Our initial observations showed that NPM-IFI27, the IFI27 variant in northern pig-tailed macaque (Macaca leonina, NPM), exhibited a strong anti-HIV-1 activity. Further investigation demonstrated that NPM-IFI27 degraded p24 and p55 via the ubiquitin-proteasome pathway, with NPM-IFI27-37-115 interacting with the p24-N domain, and the NPM-IFI27-76-122 domain was closely associated with K48 ubiquitin recruitment. Additionally, Skp2 was identified as the probable E3 ubiquitin ligase responsible for the degradation of p24 and p55. Similarly, human IFI27 (Hu-IFI27) showed a mechanism similar to NPM-IFI27 in HIV-1 inhibition. These findings underscore the pivotal role of NPM-IFI27 in HIV-1 infection and provide a potential strategy for clinical anti-HIV-1 therapy.IMPORTANCEHIV-1 infection can trigger the production of IFN-I, which subsequently activates the expression of various IFN-stimulated genes (ISGs) to antagonize the virus. Therefore, discovering novel host antiviral agents for HIV-1 treatment is crucial. Our previous study revealed that IFI27 can influence HIV-1 replication. In this study, we observed that the NPM-IFI27 complex specifically inhibited HIV-1 by targeting its Gag protein. Further exploration demonstrated that IFI27 interacted with the HIV-1 p24 and p55 proteins, leading to their degradation through the ubiquitin-proteasome pathway. Notably, the NPM-IFI27-37-122 variant exhibited potent anti-HIV-1 activity, comparable to that of SAMHD1. These findings highlight the critical role and inhibitory mechanism of NPM-IFI27 in HIV-1 infection, providing a potential strategy for clinical antiviral therapy.

Lead-Free Hybrid Perovskite: An Efficient Room-Temperature Spin Generator via Large Interfacial Rashba Effect.

Two-dimensional (2D) hybrid organic-inorganic perovskite (HOIP) shows great potential for developing flexible and wearable spintronic devices by serving as spin sources via the bulk Rashba effect (BRE). However, the practical application of BRE in 2D HOIP faces huge challenges, particularly due to the toxicity of lead, which is crucial for achieving large spin-orbit coupling, and the restrictions in 2D HOIP candidates to meet specific symmetry-breaking requirements. To overcome these obstacles, we designed a strategy to exploit the interfacial Rashba effect (IRE) of lead-free 2D HOIP (C6H5CH2CH2NH3)2CuCl4 (PEA-CuCl), manifesting as an efficient spin generator at room temperature. IRE of PEA-CuCl originates from the large orbital hybridization at the interface between PEA-CuCl and adjacent ferromagnetic layers. Spin-torque ferromagnetic resonance measurements further quantify a large Rashba effective field of 14.04 Oe per 1011 A m-2, surpassing those of lead-based HOIP and traditional all-inorganic heterojunctions with noble metals. Our lead-free 2D HOIP PEA-CuCl, which harnesses large IRE for spin generation, is efficient, nontoxic, and economic, offering huge promise for future flexible and wearable spintronic devices.