Search

Emerging ferroelectric and antiferroelectric HfO2-based thin films are attractive candidates for energy conversion and storage applications. In this work, the polar phase transformation between tetragonal and orthorhombic phases associated with ferroelectric or antiferroelectric behaviors is utilized to manipulate the electrocaloric cooling and energy storage performances in Zr-doped, woken up HfO2 ultrathin films. A giant electrocaloric temperature change of up to 11.85 K in Hf0.5Zr0.5O2 with the morphotropic phase boundary (MPB) state and a high energy storage density of 39.34 J/cm3 in the tetragonal phase-dominant Hf0.25Zr0.75O2 system are obtained. More interestingly, contrary to overdoping and excessive electric fields, an appropriate Zr concentration of 0.5 and an applicable driving field of 1.91 MV/cm are desired for the electrocaloric effect, resulting in an ultralow operating voltage as low as 1.3 V in this 6.8 nm thick Hf0.5Zr0.5O2 film. These findings illustrate that the structural design strategy is a visible method for achieving optimal energy-related behaviors and highlight the great possibilities for building future energy-related devices.

Abstract Background Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear. Methods The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro. Results In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice. Conclusions Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases.

The utilization of Bacillus sp. for the production of bio-CaCO3 in concrete crack repair and strength enhancement has attracted considerable attention. However, microbial-induced calcium carbonate precipitation (MICP) has yet to be explored as a precedent with activated sludge. Here calcium sourced from concrete slurry waste (CSW) and carbon from sludge microbial β-oxidation under alkaline were used to generate micro/nano CaCO3. The results indicate that the main crystalline form of the generated precipitated particles is calcite, with a particle size ranging from 0.7 to 10 μm. Minimal heavy metals were found in the supernatant following settling. And at the optimum pH of 8.5–9, carbon capture reached 743 mg L−1, and CaCO3 production reached 1,191 mg L−1, and dominant phylum were Proteobacteria and Bacteroidota, with Thauera being a prevalent genus adept in β-oxidation. Mass balance analysis showed that alkali promotes microbial β-oxidation of organisms to produce CO2 and facilitate storage. Thus, the alkaline regulation of metabolism between microbe and CSW provides a novel way of sludge to initiate MICP. HIGHLIGHTS Utilizing concrete slurry waste as a calcium source and sludge β-oxidation as a carbon source can successfully produce bio-CaCO3.; pH 8.5–9 is the optimal alkaline control for Thauera to be the dominant genus undergoing β-oxidation to produce CO2.; Bio-CaCO3 is a 0.7–10 μm calcite particle, which is an excellent material for repairing concrete.; There is no risk of heavy metal leakage during operation.;

We investigate the existence of ground states for a class of Schrödinger equations with both a standard power nonlinearity and delta nonlinearity concentrated at finite vertices of the periodic metric graphs $ G $. Using variational methods, if $ \alpha > 0 $ and the standard nonlinearity power is $ L^{2}- $subcritical, we establish the existence of ground states for every mass and every periodic graph. If $ \alpha < 0 $ and the standard nonlinearity power is $ L^{2}- $critical, we show that two types of topological structures on $ G $ will prevent the existence of ground states. Furthermore, for graphs that do not satisfy these two types of topological structures, ground states exist when the given mass belongs to an appropriate range and the parameter $ \left | \alpha \right| $ is small enough.

Human urine, which is high in nutrients, acts as a resource as well as a contaminant. Indiscriminate urine discharge causes environmental pollution and wastes resources. To elucidate the research status and developmental trajectory of source-separated urine (SSU) treatment and recovery, this study was based on the Web of Science Core Collection (WOSCC) database and used the bibliometric software VOSviewer and CiteSpace to conduct a comprehensive and in-depth bibliometric analysis of the related literature in this field. The findings revealed a general upward trend in SSU treatment and recovery from 2000 to 2023. The compendium of 894 scholarly articles predominantly focused on the disciplines of Environmental Sciences, Environmental Engineering, and Water Resources. China and the USA emerged as the foremost contributors. Keyword co-occurrence mapping, clustering, and burst analysis have shown that the recovery of nitrogen and phosphorus from urine is currently the main focus, with future prospects leaning toward the retrieval of biochemicals and chemical energy. This study systematically categorizes and compares the developmental status, current advancements, and research progress in this field. The findings of this study provide a valuable reference for understanding developmental pathways in this field of research. HIGHLIGHTS A total of 894 publications pertinent to source-separated urine (SSU) treatment and recovery was analyzed.; Bibliometric results were visualized using VOSViewer, and Citespace.; The current treatment and resource recovery technologies applied in SSU were reviewed.; The research focus and development status of SSU treatment and recovery were summarized.; This provides prospective avenues and suggestions for SSU treatment and recovery.;

Abstract The Tianshanbeilu cemetery is the largest Bronze Age cemetery in eastern Xinjiang, China, and plays important roles in connecting the Eurasian interior to the Hexi Corridor, and further to the Central Plains region. Utilizing micro-XRF and Raman spectroscopy techniques, we identified a fluorite bead at this cemetery. This barrel bead is the earliest record of such a fluorite bead in China, dating back to approximately 1385–1256 BCE. Comparing the unearthed records of fluorite beads in eastern China spanning from the Neolithic Age to the Western Zhou dynasty, we notice that in the early Western Zhou period, fluorite beads found in élite burials are only in barrel or biconical shapes, both of which first appeared in the eastern region of Xinjiang, such as the Tianshanbeilu cemetery in Hami and the Yanghai cemetery in the Turpan Basin. We proposed that the barrel fluorite bead drilled by metal tubular drill first appearing in the Tianshanbeilu cemetery might have spread eastward to the Central Plains region and finally constituted a component of the ritual revolutions during the Western Zhou dynasty.

Abstract In traditional von Neumann computing architecture, the efficiency of the system is often hindered by the data transmission bottleneck between the processor and memory. A prevalent approach to mitigate this limitation is the use of non-volatile memory for in-memory computing, with spin–orbit torque (SOT) magnetic random-access memory (MRAM) being a leading area of research. In this study, we numerically demonstrate that a precise combination of damping-like and field-like spin–orbit torques can facilitate precessional magnetization switching. This mechanism enables the binary memristivity of magnetic tunnel junctions (MTJs) through the modulation of the amplitude and width of input current pulses. Building on this foundation, we have developed a scheme for a reconfigurable spintronic logic gate capable of directly implementing Boolean functions such as AND, OR, and XOR. This work is anticipated to leverage the sub-nanosecond dynamics of SOT-MRAM cells, potentially catalyzing further experimental developments in spintronic devices for in-memory computing.

In oil and gas exploration, elucidating the complex interdependencies among geological variables is paramount. Our study introduces the application of sophisticated regression analysis method at the forefront, aiming not just at predicting geophysical logging curve values but also innovatively mitigate hydrocarbon depletion observed in geochemical logging. Through a rigorous assessment, we explore the efficacy of eight regression models, bifurcated into linear and nonlinear groups, to accommodate the multifaceted nature of geological datasets. Our linear model suite encompasses the Standard Equation, Ridge Regression, Least Absolute Shrinkage and Selection Operator, and Elastic Net, each presenting distinct advantages. The Standard Equation serves as a foundational benchmark, whereas Ridge Regression implements penalty terms to counteract overfitting, thus bolstering model robustness in the presence of multicollinearity. The Least Absolute Shrinkage and Selection Operator for variable selection functions to streamline models, enhancing their interpretability, while Elastic Net amalgamates the merits of Ridge Regression and Least Absolute Shrinkage and Selection Operator, offering a harmonized solution to model complexity and comprehensibility. On the nonlinear front, Gradient Descent, Kernel Ridge Regression, Support Vector Regression, and Piecewise Function-Fitting methods introduce innovative approaches. Gradient Descent assures computational efficiency in optimizing solutions, Kernel Ridge Regression leverages the kernel trick to navigate nonlinear patterns, and Support Vector Regression is proficient in forecasting extremities, pivotal for exploration risk assessment. The Piecewise Function-Fitting approach, tailored for geological data, facilitates adaptable modeling of variable interrelations, accommodating abrupt data trend shifts. Our analysis identifies Ridge Regression, particularly when augmented by Piecewise Function-Fitting, as superior in recouping hydrocarbon losses, and underscoring its utility in resource quantification refinement. Meanwhile, Kernel Ridge Regression emerges as a noteworthy strategy in ameliorating porosity-logging curve prediction for well A, evidencing its aptness for intricate geological structures. This research attests to the scientific ascendancy and broad-spectrum relevance of these regression techniques over conventional methods while heralding new horizons for their deployment in the oil and gas sector. The insights garnered from these advanced modeling strategies are set to transform geological and engineering practices in hydrocarbon prediction, evaluation, and recovery.

Abstract Backgroud Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell‐free DNA (cfDNA) in patients with non‐small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell‐free RNA (cfRNA) is critical for resolving the issue. Methods A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT‐qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi‐gene mutations detection by RT‐qPCR. Results Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4‐ALK, ROS1, RET fusions, and MET ex14 skipping. Conclusion These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA‐based assay.

Summary: The impact of dietary nutrients on tumor immunity remains an area of ongoing investigation, particularly regarding the specific role of vitamins and their mechanism. Here, we demonstrate that vitamin B3 (VB3) induces antitumor immunity against liver cancer through biased GPR109A axis in myeloid cell. Nutritional epidemiology studies suggest that higher VB3 intake reduces liver cancer risk. VB3 supplementation demonstrates antitumor efficacy in multiple mouse models through alleviating the immunosuppressive tumor microenvironment (TME) mediated by tumor-infiltrating myeloid cell, thereby augmenting effectiveness of immunotherapy or targeted therapy in a CD8+ T cell-dependent manner. Mechanically, the TME induces aberrant GPR109A/nuclear factor κB (NF-κB) activation in myeloid cell to shape the immunosuppressive TME. In contrast, VB3 activates β-Arrestin-mediated GPR109A degradation and NF-κB inhibition to suppress the immunosuppressive polarization of myeloid cell, thereby activating the cytotoxic function of CD8+ T cell. Overall, these results expand the understanding of how vitamins regulate the TME, suggesting that dietary VB3 supplementation is an adjunctive treatment for liver cancer.

A powder-metallurgy MoNbTaTiV refractory high-entropy alloy synthesized by mechanical alloying (MA) and spark plasma sintering was subjected to hot deformations at different temperatures and strain rates. The microstructural morphologies were characterized, and component element segregation was elucidated. With grain refinement and lattice strain increase, the large inhomogeneous milled powder became refined and homogeneous after the MA. Component element segregation was observed at relatively low deformation temperatures and high strain rates. As the deformation temperature increased and the strain rate decreased, the segregation gradually disappeared, which was attributed to dislocation movement.

Summary: It is important to understand the geometry of genome space in biology. After transforming genome sequences into frequency matrices of the chaos game representation (FCGR), we regard a genome sequence as a point in a suitable Grassmann manifold by analyzing the column space of the corresponding FCGR. To assess the sequence similarity, we employ the generalized Grassmannian distance, an intrinsic geometric distance that differs from the traditional Euclidean distance used in the classical k-mer frequency-based methods. With this method, we constructed phylogenetic trees for various genome datasets, including influenza A virus hemagglutinin gene, Orthocoronavirinae genome, and SARS-CoV-2 complete genome sequences. Our comparative analysis with multiple sequence alignment and alignment-free methods for large-scale sequences revealed that our method, which employs the subspace distance between the column spaces of different FCGRs (FCGR-SD), outperformed its competitors in terms of both speed and accuracy. In addition, we used low-dimensional visualization of the SARS-CoV-2 genome sequences and spike protein nucleotide sequences with our methods, resulting in some intriguing findings. We not only propose a novel and efficient algorithm for comparing genome sequences but also demonstrate that genome data have some intrinsic manifold structures, providing a new geometric perspective for molecular biology studies.

Background: The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response. Aims: To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8+-TILs) in patients with HER2-positive BC. Study Design: Retrospective cohort study. Methods: This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8+-TILlow (< 35%) and CD8+-TILhigh (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8+-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility. Results: Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8+-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (p = 0.009, US_ADC vs. US; p

NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in most solid cancers, emerging as a promising target for tumor-selective killing. β-Lapachone (β-Lap), an NQO1 bioactivatable drug, exhibits significant antitumor effects on NQO1-positive cancer cells by inducing immunogenic cell death (ICD) and enhancing tumor immunogenicity. However, the interaction between β-Lap-mediated antitumor immune responses and neutrophils, novel antigen-presenting cells (APCs), remains unknown. This study demonstrates that β-Lap selectively kills NQO1-positive murine tumor cells by significantly increasing intracellular ROS formation and inducing DNA double strand breaks (DSBs), resulting in DNA damage. Treatment with β-Lap efficiently eradicates immunocompetent murine tumors and significantly increases the infiltration of tumor-associated neutrophils (TANs) into the tumor microenvironment (TME), which plays a crucial role in the drug’s therapeutic efficacy. Further, the presence of β-Lap-induced antigen medium leads bone marrow-derived neutrophils (BMNs) to directly kill murine tumor cells, aiding in dendritic cells (DCs) recruitment and significantly enhancing CD8+ T cell proliferation. β-Lap treatment also drives the polarization of TANs toward an antitumor N1 phenotype, characterized by elevated IFN-β expression and reduced TGF-β cytokine expression, along with increased CD95 and CD54 surface markers. β-Lap treatment also induces N1 TAN-mediated T cell cross-priming. The HMGB1/TLR4/MyD88 signaling cascade influences neutrophil infiltration into β-Lap-treated tumors. Blocking this cascade or depleting neutrophil infiltration abolishes the antigen-specific T cell response induced by β-Lap treatment. Overall, this study provides comprehensive insights into the role of tumor-infiltrating neutrophils in the β-Lap-induced antitumor activity against NQO1-positive murine tumors.

Abstract Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi‐omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population‐specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon‐stimulated genes (ISGs). Validation through multi‐immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune‐negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi‐omics analysis integrating bulk transcriptomic, single‐cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.

This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.

Abstract Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

It has long been asserted that failure to recover from central nervous system diseases is due to the system’s intricate structure and the regenerative incapacity of adult neurons. Yet over recent decades, numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system, including humans’. This has challenged the long-held scientific consensus that the number of adult neurons remains constant, and that new central nervous system neurons cannot be created or renewed. Herein, we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury, and describe novel treatment strategies that target endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury. Central nervous system injury frequently results in alterations of endogenous neurogenesis, encompassing the activation, proliferation, ectopic migration, differentiation, and functional integration of endogenous neural stem cells. Because of the unfavorable local microenvironment, most activated neural stem cells differentiate into glial cells rather than neurons. Consequently, the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function. Scientists have attempted to enhance endogenous neurogenesis using various strategies, including using neurotrophic factors, bioactive materials, and cell reprogramming techniques. Used alone or in combination, these therapeutic strategies can promote targeted migration of neural stem cells to an injured area, ensure their survival and differentiation into mature functional neurons, and facilitate their integration into the neural circuit. Thus can integration replenish lost neurons after central nervous system injury, by improving the local microenvironment. By regulating each phase of endogenous neurogenesis, endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons. This offers a novel approach for treating central nervous system injury.

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

Due to the problem of a small amount of EEG samples and relatively high dimensionality of electroencephalogram (EEG) features, feature selection plays an essential role in EEG-based emotion recognition. However, current EEG-based emotion recognition studies utilize a problem transformation approach to transform multi-dimension emotional labels into single-dimension labels, and then implement commonly used single-label feature selection methods to search feature subsets, which ignores the relations between different emotional dimensions. To tackle the problem, we propose an efficient EEG feature selection method for multi-dimension emotion recognition (EFSMDER) via local and global label relevance. First, to capture the local label correlations, EFSMDER implements orthogonal regression to map the original EEG feature space into a low-dimension space. Then, it employs the global label correlations in the original multi-dimension emotional label space to effectively construct the label information in the low-dimension space. With the aid of local and global relevance information, EFSMDER can conduct representational EEG feature subset selection. Three EEG emotional databases with multi-dimension emotional labels were used for performance comparison between EFSMDER and fourteen state-of-the-art methods, and the EFSMDER method achieves the best multi-dimension classification accuracies of 86.43, 84.80, and 97.86 percent on the DREAMER, DEAP, and HDED datasets, respectively.

Flexible hafnia-based ferroelectric memories are arousing much interest with the ever-growing demands for nonvolatile data storage in wearable electronic devices. Here, high-quality flexible Hf0.5Zr0.5O2 membranes with robust ferroelectricity were fabricated on inorganic pliable mica substrates via an atomic layer deposition technique. The flexible Hf0.5Zr0.5O2 thin membranes with a thickness of ∼8 nm exhibit a high remanent polarization of ∼16 μC/cm2, which possess very robust polarization switching endurance (>1010 cycles, two orders of magnitude better than reported flexible HfO2-based films) and superior retention ability (expected >10 years). In particular, stable ferroelectric polarization as well as excellent endurance and retention performance show negligible degradations under 6 mm radius bending conditions or after 104 bending cycles with a 6 mm bending radius. These results mark a crucial step in the development of flexible hafnium oxide-based ferroelectric memories for wearable electronic devices.

[INLINE:1] Neurotrophic keratopathy is a persistent defect of the corneal epithelium, with or without stromal ulceration, due to corneal nerve deficiency caused by a variety of etiologies. The treatment options for neurotrophic keratopathy are limited. In this study, an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor (CTH-mNGF). Its effectiveness was evaluated in corneal denervation (CD) mice and patients with neurotrophic keratopathy. In the preclinical setting, CTH-mNGF was assessed in a murine corneal denervation model. CTH-mNGF was transparent, thermosensitive, and ensured sustained release of mNGF for over 20 hours on the ocular surface, maintaining the local mNGF concentration around 1300 pg/mL in vivo. Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice. A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy. Patients received topical CTH-mNGF twice daily for 8 weeks. Fluorescein sodium images, Schirmer’s test, intraocular pressure, Cochet-Bonnet corneal perception test, and best corrected visual acuity were evaluated. In total, six patients (total of seven eyes) diagnosed with neurotrophic keratopathy were enrolled. After 8 weeks of CTH-mNGF treatment, all participants showed a decreased area of corneal epithelial defect, as stained by fluorescence. Overall, six out of seven eyes had fluorescence staining scores < 5. Moreover, best corrected visual acuity, intraocular pressure, Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement. An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes. This study demonstrates that CTH-mNGF is transparent, thermosensitive, and has sustained-release properties. Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy, being convenient and cost effective.

Stroke can cause Wallerian degeneration in regions outside of the brain, particularly in the corticospinal tract. To investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke, we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal tract. We first used a routine, sensitive marker of axonal injury, amyloid precursor protein, to examine Wallerian degeneration of the corticospinal tract. An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex, with no positive signal in distal parts of the corticospinal tract, at all time points. To improve visualization of Wallerian degeneration, we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing axons. Using this approach, we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke. In addition, microglia mobilized and activated early, from day 7 after stroke, but did not maintain a phagocytic state over time. Meanwhile, astrocytes showed relatively delayed mobilization and a moderate response to Wallerian degeneration. Moreover, no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal tract. In conclusion, our data provide evidence for dynamic, pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation, differentiation, migration, and survival, as well as angiogenesis, in the context of brain injury. However, whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown. In this study, we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats. The gel slowly released basic fibroblast growth factor, which improved the local microenvironment, activated endogenous neural stem/progenitor cells, and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons, while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery. This study revealed the mechanism by which bioactive materials repair ischemic strokes, thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Due to its high power-to-weight ratio, low weight, and silent operation, shape memory alloy (SMA) is widely used as a muscle-like soft actuator in intelligent bionic robot systems. However, hysteresis nonlinearity and multi-valued mapping behavior can severely impact trajectory tracking accuracy. This paper proposes an adaptive nonsingular fast terminal sliding mode control (ANFTSMC) scheme aimed at enhancing position tracking performance in SMA-actuated systems by addressing hysteresis nonlinearity, uncertain dynamics, and external disturbances. Firstly, a simplified third-order actuator model is developed and a variable gain extended state observer (VGESO) is employed to estimate unmodeled dynamics and external disturbances within finite time. Secondly, a novel nonsingular fast terminal sliding mode control (NFTSMC) law is designed to overcome singularity issues, reduce chattering, and guarantee finite-time convergence of the system states. Finally, the ANFTSMC scheme, integrating NFTSMC with VGESO, is proposed to achieve precise position tracking for the prosthetic hand. The convergence of the closed-loop control system is validated using Lyapunov’s stability theory. Experimental results demonstrate that the external pulse disturbance error of ANFTSMC is 8.19°, compared to 19.21° for the comparative method. Furthermore, the maximum absolute error for ANFTSMC is 0.63°, whereas the comparative method shows a maximum absolute error of 1.03°. These results underscore the superior performance of the proposed ANFTSMC algorithm.

Ensuring optimal infant nutrition is crucial for the health and development of children. Many infants aged 0–6 months are fed with infant formula rather than breast milk. Research on cancer cell lines and animal models is limited to examining the nutrition effects of formula and breast milk, as it does not comprehensively consider absorption, metabolism, and the health and social determinants of the infant and its physiology. Our study utilized small intestine organoids induced from human embryo stem cell (ESC) to compare the nutritional effects of breast milk from five donors during their postpartum lactation period of 1–6 months and three types of Stage 1 infant formulae from regular retail stores. Using transcriptomics and untargeted metabolomics approaches, we focused on the differences such as cell growth and development, cell junctions, and extracellular matrix. We also analyzed the roles of pathways including AMPK, Hippo, and Wnt, and identified key genes such as ALPI, SMAD3, TJP1, and WWTR1 for small intestine development. Through observational and in-vitro analysis, our study demonstrates ESC-derived organoids might be a promising model for exploring nutritional effects and underlying mechanisms.

ObjectiveFrailty and activities of daily living (ADL) disability are common conditions among older population. Studies on the bidirectional relationship between frailty and ADL are limited. The current study examined the cross-sectional and longitudinal associations between frailty and ADL in middle-aged and older Chinese individuals.MethodsThe data was collected through the China Health and Retirement Longitudinal Study (CHARLS), conducted in 2011, 2013, and 2015, encompassing 17,284 individuals aged ≥45 years. We excluded individuals without follow-up data. 2,631 participants finished the baseline survey. The definition of ADL disability encompasses difficulty in engaging in either basic activities of daily living (BADL) or instrumental activities of daily living (IADL). Frailty was assessed according to the Fried criteria. Logistic regression was utilized to examine odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the cross-sectional relationships between ADL with frailty at baseline. The prediction effects were explored using Cox proportional hazards analysis, testing hazard ratios (HRs) and 95%CIs.ResultsIn cross-sectional analysis, BADL [OR = 6.660 (4.519–9.815)], IADL [OR = 5.950 (4.490–7.866)], and ADL [OR = 5.658 (4.278–7.483)] exhibited significant associations with frailty; frailty demonstrated significant associations with BADL [OR = 6.741 (4.574–9.933)], IADL [OR = 6.042 (4.555–8.016)] and ADL [OR = 5.735 (4.333–7.591)]. In longitudinal analysis, IADL and ADL were significantly associated with frailty in participants without baseline frailty in the short-term period [IADL: HR = 1.971 (1.150–3.379), ADL: HR = 1.920 (1.146–3.215)], IADL exhibited a significant association with frailty in the long-term period [HR = 2.056 (1.085–3.895)]. There was no significant link observed between frailty and an elevated risk of disability onset in BADL, IADL and ADL during the short-term period. When considering the long-term perspective, frailty exhibited a significant association with an elevated risk of disability onset in BADL [HR= 1.820 (1.126–2.939)] and IADL [HR = 1.724 (1.103–2.694)].ConclusionIn middle-aged and older adults, ADL and IADL disability predicted frailty after 2-year follow-up, IADL disability predicted frailty after 4-year follow-up. Moreover, frailty did not predict BADL, IADL and ADL disability after 2-year follow-up. However, frailty predicted BADL and IADL disability after 4-year follow-up.

Summary: Overactivation of osteoclasts due to altered osteoclastogenesis causes multiple bone metabolic diseases. However, how osteoclast differentiation is tightly regulated and involved in multiple pathophysiological states remains mystery. In this study, we noticed that the downregulation of BHLHE41 (basic-helix-loop-helix family member e41) was tightly associated with osteoclast differentiation and osteoporosis. Functionally, the upregulation or downregulation of BHLHE41 suppressed or promoted osteoclast differentiation, respectively, in vitro. A mechanism study indicated that the direct binding of BHLHE41 to the promoter region of NFATc1 that led to its downregulation. Notably, the inhibition of NFATc1 abrogated the enhanced osteoclast differentiation in BHLHE41-knockdown bone marrow macrophages (BMMs). Additionally, upregulation of BHLHE41 impeded bone destruction in OVX mice with osteoporosis. Therefore, our research reveals the mechanism by which BHLHE41 regulates osteoclast differentiation and bone resorption via NFATc1, and targeting BHLHE41 is a potential strategy for the treatment of osteoporosis.

Abstract Background Synaptic degeneration occurs in the early stage of Alzheimer's disease (AD) before devastating symptoms, strongly correlated with cognitive decline. Circular RNAs (circRNAs) are abundantly enriched in neural tissues, and aberrant expression of circRNAs precedes AD symptoms, significantly correlated with clinical dementia severity. However, the direct relationship between circRNA dysregulation and synaptic impairment in the early stage of AD remains poorly understood. Methods Hippocampal whole-transcriptome sequencing was performed to identify dysregulated circRNAs and miRNAs in 4-month-old wild-type and APP/PS1 mice. RNA antisense purification and mass spectrometry were utilized to unveil interactions between circRIMS2 and methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3). The roles of circRIMS2/miR-3968 in synaptic targeting of UBE2K-mediated ubiquitination of GluN2B subunit of NMDA receptor were evaluated via numerous lentiviruses followed by morphological staining, co-immunoprecipitation and behavioral testing. Further, a membrane-permeable peptide was used to block the ubiquitination of K1082 on GluN2B in AD mice. Results circRIMS2 was significantly upregulated in 4-month-old APP/PS1 mice, which was mediated by METTL3-dependent N6-methyladenosine (m6A) modification. Overexpression of circRIMS2 led to synaptic and memory impairments in 4-month-old C57BL/6 mice. MiR-3968/UBE2K was validated as the downstream of circRIMS2. Elevated UBE2K induced synaptic dysfunction of AD through ubiquitinating K1082 on GluN2B. Silencing METTL3 or blocking the ubiquitination of K1082 on GluN2B with a short membrane-permeable peptide remarkably rescued synaptic dysfunction in AD mice. Conclusions In conclusion, our study demonstrated that m6A-modified circRIMS2 mediates the synaptic and memory impairments in AD by activating the UBE2K-dependent ubiquitination and degradation of GluN2B via sponging miR-3968, providing novel therapeutic strategies for AD.

Abstract Lack of proper innate sensing inside the tumor microenvironment could reduce both innate and adaptive immunity, which remains a critical cause of immunotherapy failure in various tumor treatments. Double-stranded DNA (dsDNA) has been evidenced to be a promising immunostimulatory agent to induce type I interferons (IFN-Is) production for innate immunity activation through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, yet the unsatisfactory delivery and susceptibility to nuclease degradation hindered its feasibility for further clinical applications. Herein, we report on the constructed tumor microenvironment-responsive DNA-based nanomedicine loaded by dendritic mesoporous organosilica nanoparticles (DMONs), which provide efficient delivery of dsDNA to induce intratumoral IFN-Is production for triggering innate sensing for enhanced anti-tumor immunotherapy. Extensive in vitro and in vivo evaluations have demonstrated the dramatic IFN-Is production induced by dsDNA@DMONs in both immune cells and tumor cells, which facilitates dendritic cells (DCs) maturation and T cells activation for eliciting the potent innate immune and adaptive immune responses. Desirable biosafety and marked therapeutic efficacy with a tumor growth inhibition (TGI) of 51.0% on the murine B16-F10 melanoma model were achieved by the single agent dsDNA@DMONs. Moreover, dsDNA@DMONs combined with anti-PD-L1 antibody further enhanced the anti-tumor efficacy and led to almost complete tumor regression. Therefore, this work highlighted the immunostimulatory DNA-based nanomedicine as a promising strategy for overcoming the resistance to immunotherapy, by promoting the IFN-Is production for innate immunity activation and remodeling the tumor microenvironment. Graphical abstract

Abstract The process of staining was frequently employed to enhance or alter the color of agate beads in ancient times. One of the key challenges in studying ancient beads is comprehending the intricate techniques employed to color agate stones. An understanding of the staining mechanism from a mineralogical standpoint offers insights into the level of technological advancement in different civilizations. In this study, the mineral structure of eight ancient agate beads from Xinjiang Uygur Autonomous Region, NW China, was analyzed using Micro X-ray fluorescence (µXRF), Raman spectroscopy, Scanning Electron Microscope (SEM), and Fourier Transform Infrared (FTIR) techniques. The color, transparency, mineral phase, and surface roughness of the beads were examined, revealing variations ranging from colorless to light violet to dark violet. Raman and FTIR spectroscopy were employed to determine the SiO2 phase and the changes in optical characteristics of agate beads after artificial staining. The black color of the beads was formed by carbon penetration, while the red color was produced by heating. The coexistence of α-quartz and moganite phases in the red, the dark red, the black, the idiochromatic white and the part translucent zones of the ancient beads was confirmed by the 464 cm−1 peak of α-quartz and the 502 cm−1 peak of moganite phase. The analyzed red, the dark red, the black, the idiochromatic white and the part translucent zones exhibited remarkably similar FTIR spectral features, with two prominent bands at ~ 1097 and ~ 1187 cm−1, as well as two weak bands at 798 and 778 cm−1, indicating the presence of moganite and α-quartz in the unetched ancient beads. In contrast to the idiochromatic white appearance of natural agate, the scattered white coloration in etched beads was generated by an etching reaction. Both Raman and FTIR spectroscopy indicated the absence of moganite in etched beads, indicating that the scattered white color was produced by the loss of moganite and a portion of α-quartz, resulting in a rough surface.

Improving the efficiency of factor allocation in food production is the foundation for accelerating the formation of new quality productivity and achieving an agricultural green transformation. However, there has been no scholarly focus on their mechanisms and the interactions involved. This exploration is an important reference for enhancing the green production capacity of major grain-producing areas. In this study, 13 prefecture-level cities in Heilongjiang Province, China’s largest grain production base, were selected as the research samples. A model for identifying factor misallocation and grain green total factor productivity (AGGTFP) was constructed to identify the spatiotemporal differences in factor misallocation and green total factor productivity. A fixed effects model was used to explore the impact of single-factor misallocation and the interaction of dual-factor misallocation with AGGTFP. The results show that from 2004 to 2022, the AGGTFP in 13 prefecture-level cities in Heilongjiang Province has shown a slow growth trend. The inhibitory effects of single-factor misallocation of land, labor, and capital on green total factor productivity are sequentially enhanced. The interaction effects of capital misallocation and labor misallocation and labor misallocation and land misallocation strengthen the inhibitory effects of misallocation on the AGGTFP. Therefore, it is necessary to further promote the optimization of production factors and improve the green production capacity for grain.

Traditional rock wool fibres are susceptible to crystallization and pulverization. To mitigate this, glass fibres were produced from iron ore waste (IOW). When the ratio of Fe2+ and Fe3+ is 1:3 and the Al2O3 content is 10 wt.%, increasing the FexOy content enhances the thermal stability.At an FexOy content of 17–19% and an Al2O3 content of 10–13%, the glass transition temperature (Tg) peaked. Increasing the FexOy content from 10% to 20% enhanced the stability of Si-O and Al-O bonds and increased bridged oxygen, stabilizing the structure. Here, Fe2+ balances structural charges, while Fe3+ replaces some Al atoms in the network. When the Al2O3 content is 10–13% and the FexOy content is 17–19%, the thermal stability of the IOW rock glass reaches its optimal level. At 20% FexOy content, the structure becomes three-dimensional and cyclic, increasing polymerization. Consequently, incorporating FexOy alongside a 10% Al2O3 content improves thermal stability, supporting the development of high-stability rock wool from IOW. This approach also enhances the refractory properties of rock wool fibres within the FexOy-Al2O3-SiO2-MgO-CaO system.

Background: This study is designed to explore the correlation between multiple healthy lifestyles within the framework of “lifestyle medicine”, and the mortality risk of nonalcoholic fatty liver disease (NAFLD). Methods: The National Health and Nutrition Examination Survey (NHANES) database was employed. The analysis consisted of 5542 participants with baseline NAFLD and 5542 matched non-NAFLD participants from the database. Lifestyle information, including five low risk factors advocated by lifestyle medicine (healthy diet, vigorous physical activity, healthy sleep duration, avoiding smoking, and maintaining a non-depressed psychological status), was collected through a baseline questionnaire. Cox proportional hazards regression models and Kaplan–Meier survival curve were used to evaluate risk of mortality. In addition, subgroups were analyzed according to gender, age, body mass index and waist circumference. Results: In total, 502 deaths (n = 181 deaths from cardiovascular disease (CVD)) were recorded among NAFLD participants after the median follow up duration of 6.5 years. In the multivariate-adjusted model, compared to participants with an unfavorable lifestyle (scoring 0–1), NAFLD participants with a favorable lifestyle (scoring 4–5) experienced a 56% reduction in all-cause mortality and a 66% reduction in CVD mortality. Maintaining an undepressed psychological state and adhering to vigorous exercise significantly reduced CVD mortality risk in NAFLD participants (HR, 0.64 [95% CI, 0.43–0.95]; HR, 0.54 [95% CI, 0.33–0.88]) while maintaining healthy sleep reduced premature mortality due to CVD by 31%. Conclusions: Healthy lifestyle, characterized by maintaining an undepressed mental state and healthy sleep, significantly mitigates the risk of all-cause, CVD, and premature mortality risk among NAFLD patients, with a particularly pronounced effect observed in female and obese subpopulations.

Acid mine drainage (AMD), arising from mineral resource exploitation, has transformed into a significant global environmental issue for the mining sector, posing considerable risks to water, soil, ecosystems, and human health. In this study, the current status and cutting-edge dynamics of AMD remediation research were evaluated using a bibliometrics approach. Publications on AMD remediation were collected from the Web of Science Core Collection (WOSCC) database, and the relevant literature was analyzed quantitatively using various statistical methods, including keyword co-occurrence and burst analysis. In total, 2743 articles related to AMD remediation published from 1990 to 2023 were obtained. The number of publications tended to increase annually, with a relatively fast rate of increase in recent years. Recent research related to AMD remediation has mainly focused on the ecological risks, the environmental geochemical cycling, the application of sulfate-reducing bacteria and adsorption, and the recovery of heavy metals (HMs) and rare earth elements (REEs). It is anticipated that these topics of AMD remediation research are expected to be at the forefront of future research endeavors. In addition, the current status, advantages, and challenges of AMD remediation technologies are discussed from both active and passive management perspectives, providing a theoretical basis and reference for AMD remediation.

Lung cancer is a major global health concern with a low survival rate, often due to late-stage diagnosis. Liquid biopsy offers a non-invasive approach to cancer detection and monitoring, utilizing various features of circulating cell-free DNA (cfDNA). In this study, we established two models based on cfDNA coverage patterns at the transcription start sites (TSSs) from 6X whole-genome sequencing: an Early Cancer Screening Model and an EGFR mutation status prediction model. The Early Cancer Screening Model showed encouraging prediction ability, especially for early-stage lung cancer. The EGFR mutation status prediction model exhibited high accuracy in distinguishing between EGFR-positive and wild-type cases. Additionally, cfDNA coverage patterns at TSSs also reflect gene expression patterns at the pathway level in lung cancer patients. These findings demonstrate the potential applications of cfDNA coverage patterns at TSSs in early cancer screening and in cancer subtyping.

Abstract Magnetic skyrmions, topological quasiparticles, are small stable magnetic textures that possess intriguing properties and potential for data storage applications. Hybrid nanostructures comprised of skyrmions and soft magnetic material can offer additional advantages for developing skyrmion-based spintronic and magnonic devices. We show that a Néel-type skyrmion confined within a nanodot placed on top of a ferromagnetic in-plane magnetized stripe produces a unique and compelling platform for exploring the mutual coupling between magnetization textures. The skyrmion induces an imprint upon the stripe, which, in turn, asymmetrically squeezes the skyrmion in the dot, increasing their size and the range of skyrmion stability at small values of Dzyaloshinskii–Moriya interaction, as well as introducing skyrmion bi-stability. Finally, by exploiting the properties of the skyrmion in a hybrid system, we demonstrate unlimited skyrmion transport along a racetrack, free of the skyrmion Hall effect.

Abstract Due to the inherent disorder and fluidity of water, precise machining of water through laser cutting are challenging. Herein we report a strategy that realizes the laser cutting machining of water through constructing hydrophobic silica nanoparticle-encased water pancakes with sub-millimeter depth. Through theoretical analysis, numerical simulation, and experimental studies, the developed process of nanoparticle-encased water pancake laser cutting and the parameters that affect cutting accuracy are verified and elucidated. We demonstrate that laser-fabricated water patterns can form diverse self-supporting chips (SSCs) with openness, transparency, breathability, liquid morphology, and liquid flow control properties. Applications of laser-fabricated SSCs to various fields, including chemical synthesis, biochemical sensing, liquid metal manipulation, patterned hydrogel synthesis, and drug screening, are also conceptually demonstrated. This work provides a strategy for precisely machining water using laser cutting, addressing existing laser machining challenges and holding significance for widespread fields involving fluid patterning and flow control in biological, chemical, materials and biomedical research.

Abstract Skyrmions and skyrmioniums are topologically non-trivial spin textures found in chiral magnetic systems. Understanding the dynamics of these particle-like excitations is crucial for leveraging their diverse functionalities in spintronic devices. This study investigates the dynamics and evolution of chiral spin textures in [Pt/Co]3/Ru/[Co/Pt]3 multilayers with ferromagnetic interlayer exchange coupling. By precisely controlling the excitation and relaxation processes through combined magnetic field and electric current manipulation, reversible conversion between skyrmions and skyrmioniums is achieved. Additionally, we observe the topological conversion from a skyrmionium to a skyrmion, characterized by the sudden emergence of the skyrmion Hall effect. The experimental realization of reversible conversion between distinct magnetic topological spin textures represents a significant development that promises to expedite the advancement of the next generation of spintronic devices.

Abstract Despite the remarkable clinical efficacy of cancer immunotherapy, considerable patients fail to benefit from it due to primary or acquired resistance. Tumours frequently hijack diverse epigenetic mechanisms to evade immune detection, thereby highlighting the potential for pharmacologically targeting epigenetic regulators to restore the impaired immunosurveillance and re‐sensitise tumours to immunotherapy. Herein, we demonstrated that KDM4‐targeting chemotherapeutic drug JIB‐04, epigenetically triggered the tumour‐intrinsic innate immune responses and immunogenic cell death (ICD), resulting in impressive antitumour effects. Specifically, JIB‐04 induced H3K9 hypermethylation through specific inhibition of the KDM4 family (KDM4A–D), leading to impaired DNA repair signalling and subsequent DNA damage. As a result, JIB‐04 not only activated the tumour‐intrinsic cyclic GMP‐AMP synthase (cGAS)‐STING pathway via DNA‐damage‐induced cytosolic DNA accumulation, but also promoted ICD, releasing numerous damage‐associated molecular patterns. Furthermore, JIB‐04 induced adaptive resistance through the upregulation of programmed death‐ligand 1 (PD‐L1), which could be overcome with additional PD‐L1 blockade. In human tumours, KDM4B expression was negatively correlated with clinical outcomes, type I interferon signatures, and responses to immunotherapy. In conclusion, our results demonstrate that targeting KDM4 family can activate tumour‐intrinsic innate sensing and immunogenicity, and synergise with immunotherapy to improve antitumour outcomes.

Celastrol is a quinone methyl triterpenoid monomeric ingredient extracted from the root of Tripterygium wilfordii. Celastrol shows potential pharmacological activities in various diseases, which include inflammatory, obesity, cancer, and bacterial diseases. However, the application prospect of celastrol is largely limited by its low bioavailability, poor water solubility, and undesired off-target cytotoxicity. To address these problems, a number of drug delivery methods and technologies have been reported to enhance the efficiency and reduce the toxicity of celastrol. We classified the current drug delivery technologies into two parts. The direct chemical modification includes nucleic acid aptamer–celastrol conjugate, nucleic acid aptamer–dendrimer–celastrol conjugate, and glucolipid–celastrol conjugate. The indirect modification includes dendrimers, polymers, albumins, and vesicular carriers. The current technologies can covalently bond or encapsulate celastrol, which improves its selectivity. Here, we present a review that focalizes the recent advances of drug delivery strategies in enhancing the efficiency and reducing the toxicity of celastrol.

IntroductionMyocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant.MethodsMyocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit. Among 772 elderly Omicron-infected patients, categorized into myocardial injury (n = 263) and non-myocardial injury (n = 509) groups. The stratified log-rank statistic was used to compare the probability of patients developing intensive care. Receiver operating characteristic curves were used to determine the best cut-off values of clinical and laboratory data for predicting myocardial injury. Univariate and multivariate logistic regression was adopted to analyze the risk factors for myocardial injury.ResultsThe occurrence of myocardial injury in Omicron variant-infected geriatric patients was up to 34.07% and these patients may have a higher rate of requiring intensive care (P 22.69 pg/ml, procalcitonin > 0.0435 ng/ml, D-dimer > 0.615 mg/L, and sCr > 81.30 μmol/L.ConclusionThis study revealed the clinical characteristics and potential risk factors associated with myocardial injury that enable early diagnosis of myocardial injury in Omicron variant-infected elderly patients, providing important reference indicators for early diagnosis and timely clinical intervention.

Rice sheath blight is a fungal disease caused mainly by Rhizoctonia solani AG1-IA. Toxins are a major pathogenic factor of R. solani, and some studies have reported their toxin components; however, there is no unified conclusion. In this study, we reported the toxin components and their targets that play a role in R. solani AG1-IA. First, toxins produced by R. solani AG1-IA were examined. Several important phytotoxins, including benzoic acid (BZA), 5-hydroxymethyl-2-furanic aid (HFA), and catechol (CAT), were identified by comparative analysis of secondary metabolites from AG1-IA, AG1-IB, and healthy rice. Follow-up studies have shown that the toxin components of this fungus can rapidly disintegrate the biofilm structure while maintaining the content of host plant membrane components, thereby affecting the organelles, which may also explain the lack of varieties highly resistant to sheath blight.

BackgroundThe Chinese government has ended the “dynamic zero-COVID” policy, and residents are now living together with the SARS-CoV-2 virus. Only a limited number of studies have investigated the specific content and structure of COVID-19-related risk perceptions, as well as their underlying determinants. This study measured the residents’ risk perception of COVID-19 and analyzed the predictors of RP.MethodsWe conducted a comprehensive questionnaire-based survey among residents mostly in Beijing, using a specially designed scale consisting of 11 items to accurately measure COVID-19 risk perceptions. We then utilized multiple linear regression analysis to investigate the factors associated with risk perceptions.ResultsA total of 60,039 residents participated in the survey. Our study reveals that COVID-19-related worries are significantly influenced by other dimensions of RP (p

AimsThe aim of this study was to develop and validate a prognostic model based on clinical laboratory biomarkers for the early identification of high-risk patients who require intensive care unit (ICU) admission among those hospitalized with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complicated with myocardial injury (MI).MethodsThis single-center study enrolled 263 hospitalized patients with confirmed Omicron variant infection and concurrent MI. The patients were randomly divided into training and validation cohorts. Relevant variables were collected upon admission, and the least absolute shrinkage and selection operator (LASSO) was used to select candidate variables for constructing a Cox regression prognostic model. The model’s performance was evaluated in both training and validating cohorts based on discrimination, calibration, and net benefit.ResultsOf the 263 eligible patients, 210 were non-ICU patients and 53 were ICU patients. The prognostic model was built using four selected predictors: white blood cell (WBC) count, procalcitonin (PCT) level, C-reactive protein (CRP) level, and blood urea nitrogen (BUN) level. The model showed good discriminative ability in both the training cohort (concordance index: 0.802, 95% CI: 0.716–0.888) and the validation cohort (concordance index: 0.799, 95% CI: 0.681–0.917). For calibration, the predicted probabilities and observed proportions were highly consistent, indicating the model’s reliability in predicting outcomes. In the 21-day decision curve analysis, the model had a positive net benefit for threshold probability ranges of 0.2 to 0.8 in the training cohort and nearly 0.2 to 1 in the validation cohort.ConclusionIn this study, we developed a clinically practical model with high discrimination, calibration, and net benefit. It may help to early identify severe and critical cases among Omicron variant-infected hospitalized patients with MI.

Given the importance of ICT diffusion in the development of the financial sector, this analysis is an effort to analyze the transmission channels between the two in high-income and middle and low-income economies over 2001-2019. We have used three variables, including the ICT index, individuals using the internet, and mobile subscribers, to represent ICT and three indices, including the financial development index, financial institution index, and financial market index, to make our results reliable and robust. We utilized a GMM method for conducting the empirical analysis. Generally, our results imply that ICT diffusion positively impacts financial development in high-income economies and negatively impacts middle and low-income economies. Our findings suggest that middle- and low-income-economy policymakers should follow the footprint of the high-income economies and increase the role of ICT in the financial sector for its development.

IntroductionShape memory alloy (SMA) actuators are attractive options for robotic applications due to their salient features. So far, achieving precise control of SMA actuators and applying them to human-robot interaction scenarios remains a challenge.MethodsThis paper proposes a novel approach to deal with the control problem of a SMA actuator. Departing from conventional mechanism models, we attempt to describe this nonlinear plant using a gray-box model, in which only the input current and the output displacement are measured. The control scheme consists of the model parameters updating and the control law calculation. The adaptation algorithm is founded on the multi-innovation concept and incorporates a dead-zone weighted factor, aiming to concurrently reduce computational complexities and enhance robustness properties. The control law is based on a PI controller, the gains of which are designed by the pole assignment technique. Theoretical analysis proves that the closed-loop performance can be ensured under mild conditions.ResultsThe experiments are first conducted through the Beckhoff controller. The comparative results suggest that the proposed adaptive PI control strategy exhibits broad applicability, particularly under load variations. Subsequently, the SMA actuator is designed and incorporated into the hand rehabilitation robot. System position tracking experiments and passive rehabilitation training experiments for various gestures are then conducted. The experimental outcomes demonstrate that the hand rehabilitation robot, utilizing the SMA actuator, achieves higher position tracking accuracy and a more stable system under the adaptive control strategy proposed in this paper. Simultaneously, it successfully accommodates hand rehabilitation movements for multiple gestures.DiscussionThe adaptive controller proposed in this paper takes into account both the computational complexity of the model and the accuracy of the control results, Experimental results not only demonstrate the practicality and reliability of the controller but also attest to its potential application in human-machine interaction within the field of neural rehabilitation.

Background Antineoplastic chemotherapies are dramatically efficient when they provoke immunogenic cell death (ICD), thus inducing an antitumor immune response and even tumor elimination. However, activated caspases, the hallmark of most cancer chemotherapeutic agents, render apoptosis immunologically silent. Whether they are dispensable for chemotherapy-induced cell death and the apoptotic clearance of cells in vivo is still elusive.Methods A rational cell-based anticancer drug library screening was performed to explore the immunogenic apoptosis pathway and therapeutic targets under apoptotic caspase inhibition. Based on this screening, the potential of caspase inhibition in enhancing chemotherapy-induced antitumor immunity and the mechanism of actions was investigated by various cells and mouse models.Results Heat shock protein 90 (Hsp90) inhibition activates caspases in tumor cells to produce abundant genomic and mitochondrial DNA fragments and results in cell apoptosis. Meanwhile, it hijacks Caspase-9 signaling to suppress intrinsic DNA sensing. Pharmacological blockade or genetic deletion of Caspase-9 causes tumor cells to secrete interferon (IFN)-β via tumor intrinsic mitochondrial DNA/the second messenger cyclic GMP–AMP (cGAS) /stimulator of interferon genes (STING) pathway without impairing Hsp90 inhibition-induced cell death. Importantly, both Caspase-9 and Hsp90 inhibition triggers an ICD, leading to the release of numerous damage-associated molecular patterns such as high-mobility group box protein 1, ATP and type I IFNs in vitro and remarkable antitumor effects in vivo. Moreover, the combination treatment also induces adaptive resistance by upregulating programmed death-ligand 1 (PD-L1). Additional PD-L1 blockade can further overcome this acquired immune resistance and achieve complete tumor regression.Conclusions Blockade of Caspase-9 signaling selectively provokes Hsp90-based chemotherapy-mediated tumor innate sensing, leading to CD8+ T cell-dependent tumor control. Our findings implicate that pharmacological modulation of caspase pathway increases the tumor-intrinsic innate sensing and immunogenicity of chemotherapy-induced apoptosis, and synergizes with immunotherapy to overcome adaptive resistance.

The inner ear is a complex and precise auditory perception system responsible for receiving and converting sound signals into neural signals, enabling us to perceive and understand sound. However, the occurrence and development of inner ear diseases and auditory disorders, such as sensorineural hearing loss, remain a global problem. In recent years, there has been increasing research on the treatment of inner ear diseases and auditory regeneration. Among these treatments, pigment epithelium-derived factor (PEDF), as a multifunctional secretory protein, exhibits diverse biological activities and functions through various mechanisms, and has shown potential applications in the inner ear. This minireview comprehensively evaluates the performance of PEDF in sensorineural hearing loss in inner ear and its potential targets and therapeutic prospects.