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Abstract This study presents an advanced approach utilizing vacuum distillation (VD) to purify Al from Al–Mg alloys. The activity coefficients of Al-Mg binary alloy components were meticulously determined by applying the molecular interaction volume model (MIVM), non-random two-liquid (NRTL) model, and Wilson equation. Comparative analysis between experimental data and calculated activity coefficients enabled the selection of an optimal model exhibiting high computational accuracy and extensive applicability. The NRTL model, chosen for its precision, was then employed to compute the activity coefficients of Al-Mg alloy across various temperatures, leading to the development of a vapor-liquid equilibrium (VLE) diagram. This VLE diagram provides a robust quantitative foundation for assessing the purification limits of Al within the temperature range of 973–1373 K in the distillation process. Theoretical analyses underscore that VD offers a rapid and efficient method for Al purification. Experimental verification at a kilogram scale, conducted at 1373 K for 120 min, achieved an Al purity level of 99.9989% with a direct recovery efficiency of 97.98%. Notably, this VD process aligns with environmental standards for sustainable metallurgical practices, as it prevents the release of gaseous emissions or effluents, thereby meeting the industry’s growing demand for eco-friendly Al recycling methods.

Abstract Alzheimer’s disease (AD) is a highly heritable brain dementia, along with substantial failure of cognitive function. Large-scale genome-wide association studies (GWASs) have led to a set of SNPs significantly associated with AD and related traits. GWAS hits usually emerge as clusters where a lead SNP with the highest significance is surrounded by other less significant neighboring SNPs. Although functionality is not guaranteed even with the strongest associations in GWASs, lead SNPs have historically been the focus of the field, with the remaining associations inferred to be redundant. Recent deep genome annotation tools enable the prediction of function from a segment of a DNA sequence with significantly improved precision, which allows in-silico mutagenesis to interrogate the functional effect of SNP alleles. In this project, we explored the impact of top AD GWAS hits around APOE region on chromatin functions and whether it will be altered by the genetic context (i.e., alleles of neighboring SNPs). Our results showed that highly correlated SNPs in the same LD block could have distinct impacts on downstream functions. Although some GWAS lead SNPs showed dominant functional effects regardless of the neighborhood SNP alleles, several other SNPs did exhibit enhanced loss or gain of function under certain genetic contexts, suggesting potential additional information hidden in the LD blocks.

Abstract The co‐phase traction power supply system (TPSS) with hybrid energy storage system (HESS) and photovoltaic (PV) is proposed to eliminate the neutral section and improve the regenerative braking energy (RBE) utilization. Although the integration of HESS and PV facilitates the energy saving and cost reduction of the co‐phase TPSS, the high cost and configuration of HESS should be considered, which is the key to affect the optimal operation strategy of co‐phase TPSS. Here, the optimal operation strategy of co‐phase TPSS with HESS and PV is proposed to design the HESS configuration, recycle RBE and improve power quality. The proposed model aims to minimize the total system cost, including HESS investment cost, electricity cost and operation and maintenance cost. Moreover, the proposed model is formulated as a mixed integer linear programming by employing linearization approaches. Finally, case studies verify that the 29.2% cost reduction rate is achieved and the three‐phase voltage unbalance meets the standard requirements.

Beam-based additive manufacturing has challenges in fabricating pure copper due to high reflectivity. Material extrusion additive manufacturing (MEAM) avoids these issues with low costs, making it suitable to fabricate complex structures in pure copper. In this work, the effects of several printing parameters on the geometry of the samples are studied from single line, thin wall to cube using homemade copper feedstocks with high powder loading rate (65 vol%). The results show that the single line is most affected by layer thickness, while the thin wall has stricter requirements for printing temperature and printing speed. The geometric accuracy of the cube demonstrates large parametric tolerance due to the overlap and support between the lines. Central composite face-centered (CCF) design and central composite design (CCD) are used to analyze and optimize process parameters for densification. The measured porosity at the optimized printing (printing temperature = 177 °C, air gap = −0.05 mm, layer thickness = 0.3 mm) and sintering parameters (sintering temperature = 1045 °C, holding time = 4 h) is in good agreement with the predicted values. Air gap and sintering temperature have the greatest influence on the porosity, and other parameters within a certain range of on-demand adjustments do not have a significant effect. The ultimate tensile strength and elongation of the sintered samples under the optimal parameters are 153.9 ± 6.1 MPa and 31.36 ± 3.24%, respectively. No printing defects are found at the fracture and the elongation is good, showing the effectiveness of the parameter optimization.

Abstract Background We aimed to investigate the effect and potential mechanism of enhancing Neuregulin1 (NRG1)/v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 (ErbB4) expression on the differentiation of induced pluripotent stem cells (iPSCs) into cardiomyocytes. Methods We utilized CRISPR-CAS9 technology to knock in ErbB4 and obtained a single-cell clone IPSN-AAVS1-CMV-ErbB4 (iPSCs-ErbB4). Subsequently, we induced the differentiation of iPSCs into cardiomyocytes and quantified the number of beating embryoid bodies. Furthermore, quantitative real-time PCR assessed the expression of cardiomyocyte markers, including ANP (atrial natriuretic peptide), Nkx2.5 (NK2 transcription factor related locus 5), and GATA4 (GATA binding protein 4). On the 14th day of differentiation, we observed the α-MHC (α-myosin heavy chain)-positive area using immunofluorescent staining and conducted western blotting to detect the expression of cTnT (cardiac troponin) protein and PI3K/Akt signaling pathway-related proteins. Additionally, we intervened the iPSCs-ErbB4 + NRG1 group with the PI3K/Akt inhibitor LY294002 and observed alterations in the expression of cardiomyocyte differentiation-related genes. Results The number of beating embryoid bodies increased after promoting the expression of NRG1/ErbB4 compared to the iPSCs control group. Cardiomyocyte markers ANP, Nkx2.5, and GATA4 significantly increased on day 14 of differentiation, and the positive area of α-MHC was three times that of the iPSCs control group. Moreover, there was a marked increase in cTnT protein expression. However, there was no significant difference in cardiomyocyte differentiation between the iPSCs-ErbB4 group and the iPSCs control group. Akt phosphorylation was significantly increased in the iPSCs-ErbB4 + NRG1 group. LY294002 significantly reversed the enhancing effect of NRG1/ErbB4 overexpression on Akt phosphorylation as well as the increase in α-MHC and cTnT expression. Conclusions In conclusion, promoting the expression of NRG1/ErbB4 induced the differentiation of iPSC into cardiomyocytes, possibly through modulation of the PI3K/Akt signaling pathway.

Abstract PROteolysis TArgeting Chimeras (PROTACs) have been considered the next blockbuster therapies. However, due to their inherent limitations, the efficacy of PROTACs is frequently impaired by limited tissue penetration and particularly insufficient cellular internalization into their action sites. Herein, based on the ultra-pH-sensitive and enzyme-sensitive nanotechnology, a type of polymer PROTAC conjugated and pH/cathepsin B sequential responsive nanoparticles (PSRNs) are deliberately designed, following the construction of the PROTAC for Cyclin-dependent kinase 4 and 6 (CDK4/6). Colorectal cancer (CRC) which hardly responds to many treatments even immune checkpoint blockades was selected as the tumor model in this study. As a result, PSRNs were found to maintain nanostructure (40 nm) in circulation and efficiently accumulated in tumors via enhanced permeation and retention effect. Then, they were dissociated into unimers (

Abstract Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM-H3) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies. We also build a high-precision model antigen-antibody binder (A2binder) that pairs antigen epitope sequences with antibody sequences to predict binding specificity and affinity. PALM-H3-generated antibodies exhibit binding ability to SARS-CoV-2 antigens, including the emerging XBB variant, as confirmed through in-silico analysis and in-vitro assays. The in-vitro assays validate that PALM-H3-generated antibodies achieve high binding affinity and potent neutralization capability against spike proteins of SARS-CoV-2 wild-type, Alpha, Delta, and the emerging XBB variant. Meanwhile, A2binder demonstrates exceptional predictive performance on binding specificity for various epitopes and variants. Furthermore, by incorporating the attention mechanism inherent in the Roformer architecture into the PALM-H3 model, we improve its interpretability, providing crucial insights into the fundamental principles of antibody design.

Abstract The low ionic conductivity of composite solid-state electrolytes due to the lack of free Li-ions and Li dendrite growth induced by the low transference number seriously hinder their application. Herein, we find that the giant dielectric ceramic of Li0.3Ti0.02Ni0.68O (LTNO) with ultra-high dielectric constant can greatly promote the dissociation of Li salt to generate abundant movable Li-ions and realize a high room-temperature ionic conductivity (4.09 × 10–4 S cm−1) as well as a low activation energy (0.16 eV). The oxygen vacancies on the surface of LTNO can effectively immobilize the anions to achieve a high Li transference number (0.61). Furthermore, the enhanced dielectric properties of the composite electrolyte induce homogenous Li plating/stripping to suppress the growth of Li dendrites. As a result, the Li||Li symmetric cells exhibit long lifespan of 2400 h and 1150 h at 0.1 mA cm−2 and 0.2 mA cm−2, respectively. The Li||LiNi0.8Co0.1Mn0.1O2 solid-state full cells show a high capacity retention of 83% after 430 cycles at 2C. This work highlights the critical role of high dielectric property and oxygen defects of fillers in composite solid-state electrolytes, and provides a demonstration for the application of giant dielectric materials in solid-state Li metal batteries.

Study region: The Mainstream in the Tarim River Basin, Southern Xinjiang, China Study focus: Climate change and human activities have significantly altered the water cycle, and water security evaluation and management are urgent. In arid and semi-arid areas, the assessment of blue and green water is particularly important. In this study, the MIKE SHE model is used to simulate the spatial and temporal changes of blue and green water resources in the mainstream of the Tarim River Basin (TRB) from 1990 to 2050 under land use and climate change conditions. The scarcity and vulnerability of blue-green water are introduced to evaluate the water security of the basin. The impacts of different land uses on blue-green water resources were also calculated according to the model zoning. New hydrological insights for the region: The results indicate that from 1990 to 2050, blue water resources show a spatial pattern of gradual decrease from upstream to downstream. Compared to blue water, green water is dispersed more evenly over space. Future climatic scenarios will impact water security, as will changes in blue and green water security in terms of time and space. By comparing the influence of ecological water transport on the change of blue and green water before and after 2000, it was found that environmental water transport plays a certain role in improving the blue water scarcity in downstream of the TRB. The study is significant in maintaining regional water security and ecosystem stability.

ABSTRACTPre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.

Abstract Cellulose fiber-based textiles are ubiquitous in daily life for their processability, biodegradability, and outstanding flexibility. Integrating cellulose textiles with functional coating materials can unlock their potential functionalities to engage diverse applications. Metal-organic frameworks (MOFs) are ideal candidate materials for such integration, thanks to their unique merits, such as large specific surface area, tunable pore size, and species diversity. However, achieving scalable fabrication of MOFs-textiles with high mechanical durability remains challenging. Here, we report a facile and scalable strategy for direct MOF growth on cotton fibers grafted via the diazonium chemistry. The as-prepared ZIF-67-Cotton textile (ZIF-67-CT) exhibits excellent ultraviolet (UV) resistance and organic contamination degradation via the peroxymonosulfate activation. The ZIF-67-CT is also used to encapsulate essential oils such as carvacrol to enable antibacterial activity against E. coli and S. aureus. Additionally, by directly tethering a hydrophobic molecular layer onto the MOF-coated surface, superhydrophobic ZIF-67-CT is achieved with excellent self-cleaning, antifouling, and oil-water separation performances. More importantly, the reported strategy is generic and applicable to other MOFs and cellulose fiber-based materials, and various large-scale multi-functional MOFs-textiles can be successfully manufactured, resulting in vast applications in wastewater purification, fragrance industry, and outdoor gears.

Abstract The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain. Graphical Abstract

Abstract N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A is pivotal in diverse diseases especially cancer. m6A corelates with the initiation, progression, resistance, invasion, and metastasis of cancer. However, despite these insights, a comprehensive understanding of its specific roles and mechanisms within the complex landscape of cancer is still elusive. This review begins by outlining the key regulatory proteins of m6A modification and their posttranslational modifications (PTMs), as well as the role in chromatin accessibility and transcriptional activity within cancer cells. Additionally, it highlights that m6A modifications impact cancer progression by modulating programmed cell death mechanisms and affecting the tumor microenvironment through various cancer‐associated immune cells. Furthermore, the review discusses how microorganisms can induce enduring epigenetic changes and oncogenic effect in microorganism‐associated cancers by altering m6A modifications. Last, it delves into the role of m6A modification in cancer immunotherapy, encompassing RNA therapy, immune checkpoint blockade, cytokine therapy, adoptive cell transfer therapy, and direct targeting of m6A regulators. Overall, this review clarifies the multifaceted role of m6A modification in cancer and explores targeted therapies aimed at manipulating m6A modification, aiming to advance cancer research and improve patient outcomes.

Human visual attention is the basis of target recognition, change detection and classification in remote sensing images. However, the human visual attention of remote sensing images during target detection remains uninvestigated. In this study, we simultaneously collected eye tracking and electroencephalography (EEG) data of 40 experts during target detection in 1000 remote sensing images. We quantified their attention in different phases of target detection (i.e., target search, selection, and identification) from their eye movements and brain activities. The eye-tracking results indicated that hue and lightness were crucial visual features that guided visual search for remote sensing images. The size of the target also affected the allocation of human attention resources. Particularly, participants tended to miss the targets that were smaller than 3.9 % of the whole image area. The fixation event-related potentials (FRPs) in temporal and parietal brain regions further distinguished the attention of targets and distractors, which could be attributed to the process of memory and processing. Our findings offer new visual and neural evidence for human attention in target detection of remote sensing images, which not only contribute to the performance of attention-based algorithms in remote sensing interpretation, but also provide an empirical basis for guiding human–machine intelligent fusion.

Background: Prior research has demonstrated that programmed cell death (PCD) and mitochondria assume pivotal roles in controlling cellular metabolism and maintaining bone cell equilibrium. Nonetheless, the comprehensive elucidation of their mode of operation in osteoporosis (OP) warrants further investigation. Therefore, this study aimed at analyzing the role of genes associated with PCD (PCD-RGs) and mitochondria (mortality factor-related genes; MRGs) in OP.Methods: Differentially expressed genes (DEGs) were identified by subjecting the GSE56815 dataset obtained from the Gene Expression Omnibus database to differential expression analysis and comparing OP patients with healthy individuals. The genes of interest were ascertained through the intersection of DEGs, MRGs, and PCD-RGs; these genes were filtered using machine learning methodologies to discover potential biomarkers. The prospective biomarkers displaying uniform patterns and statistically meaningful variances were identified by evaluating their levels in the GSE56815 dataset and conducting quantitative real-time polymerase chain reaction-based assessments. Moreover, the functional mechanisms of these biomarkers were further delineated by constructing a nomogram, which conducted gene set enrichment analysis, explored immune infiltration, generated regulatory networks, predicted drug responses, and performed molecular docking analyses.Results: Eighteen candidate genes were documented contingent upon the intersection between 2,354 DEGs, 1,136 MRGs, and 1,548 PCD-RGs. The biomarkers DAP3, BIK, and ACAA2 were upregulated in OP and were linked to oxidative phosphorylation. Furthermore, the predictive ability of the nomogram designed based on the OP biomarkers exhibited a certain degree of accuracy. Correlation analysis revealed a strong positive correlation between CD56dim natural killer cells and ACAA2 and a significant negative correlation between central memory CD4+ T cells and DAP3. DAP3, BIK, and ACAA2 were regulated by multiple factors; specifically, SETDB1 and ZNF281 modulated ACAA2 and DAP3, whereas TP63 and TFAP2C governed DAP3 and BIK. Additionally, a stable binding force was observed between the drugs (estradiol, valproic acid, and CGP52608) and the biomarkers.Conclusion: This investigation evidenced that the biomarkers DAP3, BIK, and ACAA2 are associated with PCD and mitochondria in OP, potentially facilitate the diagnosis of OP in clinical settings.

Abstract Background Biochar is mainly used to enhance soil fertility, microbial activity, improve plant performance and reduce disease incidence. Methods A greenhouse experiment was designed to investigate the response of biochar on rhizosphere soil chemical properties, enzyme activity, microbial communities, and sugarcane Pokkah boeng disease (PB). Two sugarcane varieties Zhongzhe 9 (Z9) and ROC22, susceptible/resistant to PB, were cultivated and treated with: no biochar, 15 t ha−1 biochar, and 30 t ha−1 biochar. Results The amendment of 30 t ha−1 of biochar (B2) significantly improve soil pH by 1.50% and 9.61% compared with that of B1 and B0, followed by 0.51% increase by 15 t ha−1 of biochar (B1) compared with that of control (B0). The application of 15 t ha−1 biochar significantly increased available phosphorus (AP) and ammonium nitrogen (NH4 +–N) by 209.93 mg kg−1 and 12.1 mg kg−1, while the application of 30 t ha−1 of biochar significantly increased 241.04 mg kg−1 of available potassium (AK) (P

Abstract Natural gas distributed energy is recognized as a pivotal means to enhance energy efficiency and mitigate carbon dioxide emissions through localized energy cascading. Positioned as a key option for advancing the Sustainable Development Goals, this system optimizes energy utilization near end-users. While maximizing energy efficiency, it is imperative to address potential environmental challenges. A thorough, comprehensive environmental assessment, facilitated by the life cycle assessment method, proves instrumental in meeting this standard. Employing this method enables an intuitive grasp of the environmental strengths and weaknesses inherent in natural gas distributed energy within the power structure. This insight serves as a foundation for informed project decision-making, fostering the growth of the industry. We selected six environmental impact assessment categories based on the CML 2001 method, and conducted the life cycle analysis across four stages. China's inaugural natural gas distributed energy demonstration project was chosen as a model case, and an environmental impact assessment inventory was established, utilizing survey data and literature for comprehensive data collection and analysis. Results from case testing yield environmental impact assessment outcomes, with a specific sensitivity analysis for stages with notable environmental impact factors. The study underscores that the operation phase has the highest environmental impact, comprising 78.37% of the total combined environmental impact, followed by the fuel production phase. Comparative analyses with coal-fired and conventional natural gas power generation, based on dimensionless literature data, reveal that abiotic resources depletion potential is the primary contributor to the environmental impact of 1 kWh of electricity product, constituting 52.76% of the total impact value, followed by global warming potential. Concrete strategies have been outlined for decision-making in both the operational and planning phases of natural gas distributed energy projects. The strengthening of policies is pinpointed towards grid connection and scale expansion.

Abstract Objective To investigate the effects of metformin (MET) monotherapy and pioglitazone plus MET (PIOMET) therapy on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome (PCOS). Methods Sixty normal-weight women with PCOS were recruited between January and September 2022 at the Shengjing Hospital of China Medical University. They were randomly assigned to the MET or PIOMET groups for 12 weeks of MET monotherapy or PIOMET therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and the oral glucose insulin-releasing test (OGIRT) were performed at baseline and after the 12-week treatment. Results Thirty-six participants completed the trial. MET and PIOMET therapies improved menstrual cycles after the 4- and 12-week treatments; however, there was no statistical difference between the two groups. PIOMET therapy improved luteinizing hormone (LH), luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, and free androgen index (FAI) levels after the 4-week treatment, whereas MET monotherapy only improved total testosterone (TT) levels compared to baseline (P

Highlights Novel enzyme-induced proximity labeling technology in nanoparticles (nano-EPL). Nano-EPL enables dynamic molecular mapping of the intracellular delivery of nanoparticles in macrophages. Nano-EPL enables the elucidation of a comprehensive phagosome-centered timeline during the vesicular transportation of nanoparticles, revealing distinct organelle engagement and its differential impact on drug delivery efficiency.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Super-homogeneous functions including homogeneous functions, quasi-homogeneous functions, and several non-homogeneous functions are considered. Using the weight function method, the construction conditions of Hilbert-type multiple integral inequalities with super-homogeneous kernels are first discussed. Then, using the obtained results, the construction problem of bounded multiple integral operators with super-homogeneous kernels in weighted Lebesgue space is discussed, and the necessary and sufficient conditions for operator boundedness and the operator norm formula are obtained.

Abstract Nitrogen (N) as an inorganic macronutrient is inevitable for plant growth, development, and biomass production. Many external factors and stresses, such as acidity, alkalinity, salinity, temperature, oxygen, and rainfall, affect N uptake and metabolism in plants. The uptake of ammonium (NH4+) and nitrate (NO3−) in plants mainly depends on soil properties. Under the sufficient availability of NO3− (>1 mM), low‐affinity transport system is activated by gene network NRT1, and under low NO3− availability (

Abstract Prussian blue analogs (PBAs) are potential contestants for aqueous Mg‐ion batteries (AMIBs) on account of their high discharge voltage and three‐dimensional open frameworks. However, the low capacity arising from single reaction site severely restricts PBAs' practical applications in high‐energy‐density AMIBs. Here, an organic acid co‐coordination combined with etching method is reported to fabricate defect‐rich potassium‐free copper hexacyanoferrate with structural water on carbon nanotube fiber (D‐CuHCF@CNTF). Benefiting from the high‐valence‐state reactive sites, arrayed structure and defect effect, the well‐designed D‐CuHCF@CNTF exhibits an extraordinary reversible capacity of 146.6 mAh g−1 with two‐electron reaction, nearly close to its theoretical capacity. It is interesting to unlock the reaction mechanism of the Fe2+/Fe3+ and Cu+/Cu2+ redox couples via x‐ray photoelectron spectroscopy. Furthermore, density functional theory calculations reveal that Fe and Cu in potassium‐free D‐CuHCF participate in charge transfer during the Mg2+ insertion/extraction process. As a proof‐of‐concept demonstration, a rocking‐chair fiber‐shaped AMIBs was constructed via coupling with the NaTi2(PO4)3/CNTF anode, achieving high energy density and impressive mechanical flexibility. This work provides new possibilities to develop potassium‐free PBAs with dual‐active sites as high‐capacity cathodes for wearable AMIBs.

Background: Hydrogel carrying exosomes shows better prospects for bone regeneration. Objective: This work investigated the effect of cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes on bone regeneration in cranial defects. Methods: Cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes was prepared, and utilized to treat bone marrow mesenchymal stem cells, human umbilical vein endothelial cells, and rats with cranial defects. Logical experiments were implemented to research the effect of the prepared hydrogel on osteogenesis and angiogenesis of cells in vitro, and on bone regeneration in rats with cranial defects. Results: Cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes showed good biocompatibility and self-healing property. It promoted osteogenic differentiation of bone marrow mesenchymal stem cells and angiogenesis of human umbilical vein endothelial cells, and facilitated osteogenic differentiation, angiogenesis and bone regeneration in rats with cranial defects. Conclusion: Cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes facilitated osteogenesis, angiogenesis and bone regeneration in rats with cranial defects. It might be an effective strategy for inducing bone regeneration in individuals with cranial defects.

Background: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. Method: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. Result: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 ( I 2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 ( I 2 = 65%, 95% CI: 0.62-0.93; P

Abstract Background Single-cell multiplex imaging data have provided new insights into disease subtypes and prognoses recently. However, quantitative models that explicitly capture single-cell resolution cell-cell interaction features to predict patient survival at a population scale are currently missing. Methods We quantified hundreds of single-cell resolution cell-cell interaction features through neighborhood calculation, in addition to cellular phenotypes. We applied these features to a neural-network-based Cox-nnet survival model to identify survival-associated features. We used non-negative matrix factorization (NMF) to identify patient survival subtypes. We identified atypical subpopulations of triple-negative breast cancer (TNBC) patients with moderate prognosis and Luminal A patients with poor prognosis and validated these subpopulations by label transferring using the UNION-COM method. Results The neural-network-based Cox-nnet survival model using all cellular phenotype and cell-cell interaction features is highly predictive of patient survival in the test data (Concordance Index > 0.8). We identify seven survival subtypes using the top survival features, presenting distinct profiles of epithelial, immune, and fibroblast cells and their interactions. We reveal atypical subpopulations of TNBC patients with moderate prognosis (marked by GATA3 over-expression) and Luminal A patients with poor prognosis (marked by KRT6 and ACTA2 over-expression and CDH1 under-expression). These atypical subpopulations are validated in TCGA-BRCA and METABRIC datasets. Conclusions This work provides an approach to bridge single-cell level information toward population-level survival prediction.

Abstract Introduction Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, blocks cytokine signaling involved in psoriasis pathogenesis. This ethnic-bridging study evaluated deucravacitinib pharmacokinetics, tolerability, and safety in healthy Chinese subjects. Methods This phase I, double-blind, single-/multiple-dose study randomized healthy Chinese subjects 4:1 to a single dose of deucravacitinib 6 mg or placebo (group 1) or deucravacitinib 12 mg or placebo (group 2) on day 1; groups 1 and 2 received deucravacitinib 6 mg and 12 mg once daily, respectively, or placebo on days 5–19. Blood samples were collected on days 1–5 (0 predose–96 h postdose), day 5 (0–24 h postdose), days 9 and 12 (0 h), and day 19 (0–24 h postdose). Deucravacitinib and metabolite (BMT-153261, BMT-158170) concentrations were determined using liquid chromatography/mass spectrometry; pharmacokinetic parameters were calculated using noncompartmental analysis. Urine was collected on days 1–4 (4 h predose–96 h postdose). Safety was monitored throughout. Results Forty healthy Chinese subjects (groups 1 and 2: deucravacitinib, n = 32; placebo, n = 8) were enrolled. Deucravacitinib was rapidly absorbed after single-/multiple-dose administration, with median time to maximal plasma concentration of 1.5–2.3 h. Systemic exposure after single or multiple doses increased approximately twofold with twofold dose increase. Modest deucravacitinib accumulation was observed after multiple-dose administration (1.3- to 1.4-fold increase in area under the curve [AUC] under one dosing interval). Metabolite-to-parent ratios for maximal plasma concentration and AUC remained consistent in each dose group. Mean urinary percent recovery and renal clearance were similar between dose groups. Most adverse events (AEs) were mild/moderate, with no serious treatment-related AEs, deaths, or discontinuations due to AEs. Conclusion Deucravacitinib was safe and well tolerated in healthy Chinese subjects. Deucravacitinib exhibited rapid absorption, dose-related increases in exposure, comparable half-life, and no evidence of time-dependent pharmacokinetics, suggesting minimal effect of Chinese ethnicity on deucravacitinib pharmacokinetics. Clinical Trial Registration NCT03956953.

Abstract Background Long-range interactions between promoters and cis-regulatory elements, such as enhancers, play critical roles in gene regulation. However, the role of three-dimensional (3D) chromatin structure in orchestrating changes in transcriptional regulation during direct cell reprogramming is not fully understood. Results Here, we performed integrated analyses of chromosomal architecture, epigenetics, and gene expression using Hi-C, promoter Capture Hi-C (PCHi-C), ChIP-seq, and RNA-seq during trans-differentiation of Pre-B cells into macrophages with a β-estradiol inducible C/EBPαER transgene. Within 1h of β-estradiol induction, C/EBPα translocated from the cytoplasm to the nucleus, binding to thousands of promoters and putative regulatory elements, resulting in the downregulation of Pre-B cell-specific genes and induction of macrophage-specific genes. Hi-C results were remarkably consistent throughout trans-differentiation, revealing only a small number of TAD boundary location changes, and A/B compartment switches despite significant changes in the expression of thousands of genes. PCHi-C revealed widespread changes in promoter-anchored loops with decreased interactions in parallel with decreased gene expression, and new and increased promoter-anchored interactions in parallel with increased expression of macrophage-specific genes. Conclusions Overall, our data demonstrate that C/EBPα-induced trans-differentiation involves few changes in genome architecture at the level of TADs and A/B compartments, in contrast with widespread reorganization of thousands of promoter-anchored loops in association with changes in gene expression and cell identity.

PM2.5 poses a serious threat to human life and health, so the accurate prediction of PM2.5 concentration is essential for controlling air pollution. However, previous studies lacked the generalization ability to predict high-dimensional PM2.5 concentration time series. Therefore, a new model for predicting PM2.5 concentration was proposed to address this in this paper. Firstly, the linear rectification function with leakage (LeakyRelu) was used to replace the activation function in the Temporal Convolutional Network (TCN) to better capture the dependence of feature data over long distances. Next, the residual structure, dilated rate, and feature-matching convolution position of the TCN were adjusted to improve the performance of the improved TCN (LR-TCN) and reduce the amount of computation. Finally, a new prediction model (GRU-LR-TCN) was established, which adaptively integrated the prediction of the fused Gated Recurrent Unit (GRU) and LR-TCN based on the inverse ratio of root mean square error (RMSE) weighting. The experimental results show that, for monitoring station #1001, LR-TCN increased the RMSE, mean absolute error (MAE), and determination coefficient (R2) by 12.9%, 11.3%, and 3.8%, respectively, compared with baselines. Compared with LR-TCN, GRU-LR-TCN improved the index symmetric mean absolute percentage error (SMAPE) by 7.1%. In addition, by comparing the estimation results with other models on other air quality datasets, all the indicators have advantages, and it is further demonstrated that the GRU-LR-TCN model exhibits superior generalization across various datasets, proving to be more efficient and applicable in predicting urban PM2.5 concentration. This can contribute to enhancing air quality and safeguarding public health.

During the process of flue-curing and processing, leaves from cash crops such as tea and tobacco frequently undergo a phenomenon of browning, leading to reduced quality and significant economic losses. Despite a variety of approaches developed to suppress browning, little is known about the role that flue-curing of postharvest leaves with stems plays in delaying browning. This study investigated the impact of leaf-with-stem (LWS) flue-curing on the browning of tobacco and its underlying mechanisms. Physiological results indicated that LWS flue-curing effectively delayed browning by enhancing antioxidant capacity and maintaining reactive oxygen species (ROS) levels during the yellowing stage. Comprehensive transcriptome and metabolome analyses showed that LWS flue-curing significantly influenced various metabolic pathways. Specifically, 196, 218, and 402 metabolites, and 65, 131, and 718 genes exhibited significant changes at the 38 °C, 40 °C, and 42 °C stages, respectively, inhibiting membrane lipid degradation and enhancing the supply of reducing hydrogen through the oxidative pentose-phosphate pathway. Additionally, hormone signaling pathways were found to be associated with LWS flue-curing. These findings highlight the complex interplay of metabolic pathways and signaling networks in attenuating browning, providing valuable insights for minimizing postharvest leaf browning during flue-curing and processing.

Digital technology, acting as an engine for industrial development, propels the rapid integration of data elements and the swift iteration of digital logistics technology, significantly enhancing logistic resilience. Exploring the impact of digital technology on the resilience of logistics helps strengthen the latter’s ability to withstand external shocks. Based on the correlation between digital technology and the resilience of the logistics industry, this study measured their levels in 275 Chinese prefecture-level cities from 2011 to 2020, showing that the former significantly improved the latter, a conclusion which remained valid after robustness tests. The mechanism analysis results showed that promoting industrial collaborative agglomeration was an important part of this process, while the threshold model analysis found that the impact on resilience had nonlinear characteristics. The heterogeneity test results showed that digital technology had a significant resilience-promoting effect in the eastern and northern coastal regions, as well as in the middle reaches of the Yellow and Yangtze Rivers. Accordingly, it is necessary to accelerate digital technology integration with the logistics industry and formulate differentiated development strategies. This study provides a theoretical foundation for exploring the relationship between digital technology and logistics resilience, as well as policy recommendations.