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Hybrid manufacturing, which integrates forging and directed energy deposition (DED), offers transformative potential for fabricating large, complex titanium alloy components. Despite its promise, the inherent disparity in microstructures between the wrought substrate and DED part introduces cross-regional mechanical heterogeneity, limiting structural reliability. This study established a model to investigate the mechanical response of hybrid-manufactured Ti6Al4V with flat and curved interfaces. The model incorporates anisotropic properties of the DED part and accounts for multi-scale microstructural variations across regions. A novel numerical simulation approach is employed to capture the transitional properties of the interface, which are often simplified in traditional models. Experimental validation and finite element analysis (FEA) are combined to explore the impact of interface geometry on stress distribution and load transfer mechanisms. The evolution of stress fields under tensile loading was compared for flat and curved interfaces, revealing that stress concentration factors remain below 1.05 even under large strain conditions. However, curved interfaces exacerbate stress concentration in the central wrought substrate, elevating stress peaks at the distal end of the interface. This effect, driven by altered load transfer pathways, increases strain gradients and the risk of premature failure in the substrate. While ultimate tensile strengths for flat and curved interface specimens are comparable, the elongation of curved interfaces is reduced by approximately 10%. The findings provide a framework for optimizing interface design to improve mechanical performance, offering insights for future advancements in additive manufacturing of components with inhomogeneous microstructure.

With China′s "dual carbon" goals continuously deepening, the wind power and photovoltaic industries are experiencing steady growth, with the new energy vehicle sector rapidly developing. Meanwhile, battery energy storage technology is nearing maturity. Recently, clean energy and new energy technologies have seen rapid development, with the application market continuing to expand. The new energy sector will soon be confronted with a large number of retired or scrapped products and equipment, posing significant challenges to achieving "zero-waste cities". These wastes have dual characteristics: They are both resources and environmental concerns, and are composed of complex, diverse materials. Recovering resources and controlling pollution from these wastes have become key research areas and challenges. This article reviews the latest research, industry practices, and challenges in recovering and utilizing renewable energy solid waste, comparing and analyzing the technological characteristics of recycling solar panels, wind turbine blades, and electric vehicle batteries. It identifies suitable technologies for different product recovery needs and outlines directions for developing resource recovery and pollution control technologies for renewable energy solid waste. The goal is to support the sustainable development of the renewable energy industry and help address the challenges of renewable energy waste management.

RNA abundance is controlled by rates of synthesis and degradation. Although mis-regulation of RNA turnover is linked to neurodevelopmental disorders, how it contributes to cortical development is largely unknown. Here, we discover the landscape of RNA stability regulation in the cerebral cortex and demonstrate that intact RNA decay machinery is essential for corticogenesis in vivo. We use SLAM-seq to measure RNA half-lives transcriptome-wide across multiple stages of cortical development. Leveraging these data, we discover cis-acting features associated with RNA stability and probe the relationship between RNA half-life and developmental expression changes. Notably, RNAs that are up-regulated across development tend to be more stable, while down-regulated RNAs are less stable. Using compound mouse genetics, we discover CNOT3, a core component of the CCR4-NOT deadenylase complex linked to neurodevelopmental disease, is essential for cortical development. Conditional knockout of Cnot3 in neural progenitors and their progeny in the developing mouse cortex leads to severe microcephaly due to altered cell fate and p53-dependent apoptosis. Finally, we define the molecular targets of CNOT3, revealing it controls expression of poorly expressed, non-optimal mRNAs in the cortex, including cell cycle-related transcripts. Collectively, our findings demonstrate that fine-tuned control of RNA turnover is crucial for brain development.

Single-phase CrCoNi-based medium-entropy alloys (MEAs) have garnered considerable attention as a promising class of metallic materials. However, despite this growing interest, the dynamic mechanical response of CrCoNi-based MEAs at high strain rate remains controversial. The dynamic shear mechanical behavior of CoCrNiSi0.3 was characterized through Hopkinson-bar experiment utilizing hat-shaped specimen. In this study, a damage model based on the maximum shear strain of each slip system was chosen to describe the damage initiation and evolution. Combined with this micro-scale damage and dislocation density-based crystal plasticity theory, two constitutive models were proposed to perform predictions of the dynamic shear behavior of CoCrNiSi0.3. The strain rate effect, adiabatic temperature rising, damage evolution, and twin volume fraction during dynamic shear deformation were tracked by investigating the influence of resolved shear stress, dislocation density, texture evolution, and twinning systems shear strain. The presented model effectively predicts the deformation state of specimen, the formation and evolution of Adiabatic Shear Bands (ASBs), and the variations in strain rate and temperature at different locations within the shear region. Adiabatic Shear Bands and texture evolution are caused by the local dislocation density rising and misorientation distributions.

Abstract Background Salvia miltiorrhiza (Danshen, DS) and Radix Paeoniae Rubra (Chishao, CS) herbal pair (DS-CS) is a famous traditional Chinese combination which has been used as antithrombotic formular for centuries. However, there is still lack of sufficient scientific evidence to illustrate its underlying mechanisms. The purpose of this study is to investigate the antithrombotic effects of DS-CS extract in zebrafish and explore its possible mechanism of action. Methods The quality of traditional Chinese medicines DS and CS granules was evaluated using High Performance Liquid Chromatography (HPLC). Subsequently, the therapeutic effect of the DS-CS combination and its components, Salvianolic Acid A (SAA) and Paeoniflorin (PF), in various concentrations on thrombosis was experimentally validated. Moreover, the interaction between DS-CS and the thrombosis disease targets was analyzed through network pharmacology, predicting the potential antithrombotic mechanism of DS-CS. Molecular docking and in vivo zebrafish experiments were conducted to validate the predicted targets, with qRT-PCR utilized for target validation. Results DS-CS exhibited anti-thrombotic effect in zebrafish with concentrations ranging from 25 to 300 μg/mL. The co-administration of PF and SAA at 25 μg/mL each revealed a synergistic antithrombotic effect exceeding that of individual components when contrasted with PHZ treatment. Protein–protein interaction (PPI) analysis identified key genes, including Albumin (ALB), Proto-oncogene tyro-sine-protein kinase Src (SRC), Matrix metalloproteinase-9 (MMP9), Caspase-3 (CASP3), Epidermal growth factor receptor (EGFR), Fibroblast growth factor 2 (FGF2), Vascular endothelial growth factor receptor 2 (KDR), Matrix metalloprotein-ase-2(MMP2), Thrombin (F2), and Coagulation factor Xa (F10), associated with the antithrombotic action of PF and SAA. Furthermore, KEGG pathway analysis indicated involvement of lipid metabolism and atherosclerosis pathways. Molecular docking revealed strong binding of PF and SAA to pivotal hub genes, such as SRC, EGFR, and F10. The experimental findings demonstrated that DS-CS could upregulate the mRNA expression levels of EGFR while inhibiting F10 and SRC mRNA levels, thereby ameliorating thrombotic conditions. Conclusion This research provided valuable insights into the potential mechanisms underlying the antithrombotic activity of DS-CS. Our findings suggested that PF and SAA could be the key active ingredients responsible for this activity. The antithrombotic effects of DS-CS appeared to be mediated through the regulation of mRNA expression of SRC, EGFR, and F10. These results enhanced our understanding of DS-CS's therapeutic potential and lay the groundwork for future studies to further elucidate its mechanisms of action.

Objective Glaucoma is an optic neuropathy and the leading cause of irreversible blindness worldwide. However, the early detection of glaucoma remains challenging, as chronic forms of glaucoma remain largely asymptomatic until considerable irreversible visual field deficits have ensued. Thus, biomarkers that facilitate early diagnosis and treatment for glaucoma patients with a high risk of progression are pressing.Methods and analysis Human disease–biomarker interactions network and human disease–target–drug interactions network were first constructed based on multiomics data. The greedy search algorithm was used to search for the hub biomarkers and drug targets for glaucoma. Genome-wide association studies and epidemiological data from the UK Biobank were used to verify our results. Biological network and functional analysis was conducted to find common network features and pathways.Results We identified 10 hub biomarkers/drug targets for the diagnosis, treatment and prognosis for glaucoma. These results were verified by text mining and genomic/epidemiology data. We also predicted the new application of BMP1 and MMP9 to diagnose glaucoma and confirm the theory of hub biomarkers with multiple clinical applications. Further, relevant pivotal pathways for these hub biomolecules were discovered, which may serve as foundations for future biomarker and drug target prediction for glaucoma.Conclusion We have used a network-based approach to identify hub diagnostic and therapeutic biomarkers for glaucoma and detected relationships between glaucoma and associated diseases. Several hub biomarkers were identified and verified, which may play more important roles in the diagnosis and treatment of glaucoma.

In recent years, the Permian Maokou Formation of the Sichuan Basin shifted focus. Previously, targeting high points and exploring along the long axis were common. Now, the strategy emphasizes finding shoal grainstone reservoirs with pores, leading to significant breakthroughs and making the Maokou Formation a hotspot for exploration. This change requires strong support from sedimentary evolution studies. The eastern and northern Sichuan regions are notable for distinct tectonic and sedimentary features within the Maokou Formation, suggesting promising exploration potential. Analysis of the logging data from 386 wells was conducted and sedimentary facies analysis was carried out using field profiles and drilling cores. Combining the logging curves with sedimentary facies, the sedimentary evolution of the Maokou Formation in the study area was analyzed. Findings reveal a gentle carbonate slope from the first member to the lower submember of the second member. The stratigraphic thickness and sedimentary facies are generally influenced by the ancient Central Sichuan Palaeouplift, with low-energy shoals developing locally. A transition to a rimmed carbonate platform occurs from the upper submember of the second member to the third member, with stratigraphic thickness and sedimentary facies showing a northwest to southeast orientation. The platform develops sequentially from platform facies to platform margin, slope, and shelf facies from west to east, with high-energy shoals developing in the platform margin. Sedimentation history indicates two distinct rise to fall processes of the relative sea level during the Maokou Formation sedimentary period, corresponding to the first member to the lower submember of the second member, and the upper submember of the second member to the third member. The formation of shoal grainstone reservoirs with karst and dolomitization in the gentle slope during the first period was controlled by regional sea level changes, tectonic activities, and the type of carbonate platform. Potential hydrocarbon source rocks developed in submarine troughs during the second period. The region holds promise for unconventional oil and gas exploration, particularly on the west side of the trough with high-energy shoals on platform margins.

The transition to sustainable energy storage solutions has driven significant interest in supercapacitors, which offer high power density, rapid charge–discharge capabilities, and exceptional cycle stability. Biomass-derived carbon nanomaterials have emerged as compelling candidates for supercapacitor electrodes due to their renewable origins, environmental compatibility, and cost-effectiveness. This study explores recent advancements in tailoring structural properties, for example in preparation methods and activation, which are essential for efficient charge storage and rapid ion transport. Attention is given to the dimensional configurations—spanning 0D to 3D structures—and their impact on electrochemical behaviors. This review outlines the challenges faced in scaling up and optimizing these materials for practical applications, alongside an outlook on future research directions. By bridging the gap between material design and application demands, this work contributes to advancing sustainable supercapacitor technologies for a greener energy future.

Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

The cordierite–belite core-shell lightweight aggregate (CSLWA) effectively improves the performance of the interfacial transition zone (ITZ) in lightweight aggregate concrete; however, the underlying fracture behavior still needs to be revealed. This study characterized the reinforced mechanical properties of ITZ by CSLWA through nanoindentation and interfacial fracture tests and the reinforcement mechanism was further explained using finite element analysis. The results showed that the continuous hydration of the belite shell of CSLWA enhanced the yield stress and improved the failure strain during fracture. Energy dissipation was observed during the fracture of CSLWA concrete, improving the brittleness of the lightweight aggregate concrete. Finite element analysis showed that the core strength of CSLWA changed the energy dissipation model and affected the toughness of CSLWA concrete, and a suitable composition of 6:4 was proposed for the “cordierite–anorthite” core constitution in CSLWA depending on the strength order between the cement matrix and core of the CSLWA.

Addressing the privacy protection and data sharing issues in Chinese medical texts, this paper introduces a federated learning approach named FLCMC for Chinese medical text classification. The paper first discusses the data heterogeneity issue in federated language modeling. Then, it proposes two perturbed federated learning algorithms, FedPA and FedPAP, based on the self-attention mechanism. In these algorithms, the self-attention mechanism is incorporated within the model aggregation module, while a perturbation term, which measures the differences between the client and the server, is added to the local update module along with a customized PAdam optimizer. Secondly, to enable a fair comparison of algorithms’ performance, existing federated algorithms are improved by integrating a customized Adam optimizer. Through experiments, this paper first conducts experimental analyses on hyperparameters, data heterogeneity, and validity on synthetic datasets, which proves that the proposed federated learning algorithm has significant advantages in classification performance and convergence stability when dealing with heterogeneous data. Then, the algorithm is applied to Chinese medical text datasets to verify its effectiveness on real datasets. The comparative analysis of algorithm performance and communication efficiency shows that the algorithm exhibits strong generalization ability on deep learning models for Chinese medical texts. As for the synthetic dataset, upon comparing with comparison algorithms FedAvg, FedProx, FedAtt, and their improved versions, the experimental results show that for data with general heterogeneity, both FedPA and FedPAP show significantly more accurate and stable convergence behavior. On the real Chinese medical dataset of doctor–patient conversations, IMCS-V2, with logistic regression and long short-term memory network as training models, the experiment results show that in comparison to the above three comparison algorithms and their improved versions, FedPA and FedPAP both possess the best accuracy performance and display significantly more stable and accurate convergence behavior, proving that the method in this paper has better classification effects for Chinese medical texts.

Abstract Background Extramedullary disease usually implies a dismal outcome in relapsed/refractory multiple myeloma patients, and requires novel treatment approaches. We designed a trial using Selinexor, a nuclear export protein 1 inhibitor, together with anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell product CT103A to treat these patients, and describe the first two cases in this report. Methods Selinexor was administered with a novel two-step schedule in bridging therapy and in maintenance. The clinical responses and adverse events were recorded after CAR-T infusion and Selinexor administration. In vitro analysis of the influence of Selinexor on CAR-T cell function was performed using myeloma cell lines. Results After infusion, both patients achieved stringent complete remission (sCR), and were maintained in sCR at data-cutoff, with survival over 13 and 10 months, respectively. Neither immune effector cell-associated neurotoxicity syndrome nor over grade 2 cytokine release syndrome was observed. Meanwhile, the patients showed good tolerance to the combination. In addition, we demonstrated that low dose of Selinexor could upregulate the expression of BCMA on plasma cell lines and subsequently enhance the function of CAR-T cell in vitro. Conclusions The combination of Selinexor and CT103A exerts preliminary synergistic effect, and can be developed as a promising strategy for relapsed/refractory extramedullary myeloma.

Abstract Background The clinical applications of dispensing granules (DG) have increased dramatically. However, it is controversial whether the DG has the same quality and efficacy compared with traditional decoction (TD). In this study, the contents of main compounds, hypoglycemic effects, and potential mechanism of Coptidis Rhizoma (CR) and Scutellaria–coptis (SC), constituted of a 1:1 mixture of CR and Scutellariae Radix (SR), in the forms of TD and DG were compared. Methods The quantitative analysis was performed on an UPLC-PDA method. The 6-weeks-old male db/db mice were used as Type 2 Diabetes Mellitus (T2DM) mouse modle to investigate the antidiabetic effects of CR and SC in TD form (CR TD and SC TD), as well as CR and SC in DG form (CR DG and SC DG). Results The total content of five alkaloids in CR TD ranged from 71.00 to 78.62 mg, whereas in CR DG it ranged from 38.77 to 53.68 mg in CR DG per 1 g of decoction pieces. Compared to CR TD, CR DG exhibited a 36% reduction on average. For SC samples, the precipitation occurred in the processing of TD but not in the DG, and the relative ratio of alkaloids to flavonoids was determined to be 1:1 in TD and 1:2 in DG. Furthermore, the animal experiments showed that the CR DG (equivalent to 3 g decoction pieces/kg) had almost the same hypoglycemic effect as CR TD when they were administered for 6 weeks. Compared with SC DG (equivalent to 6 g decoction pieces/kg), SC TD showed a better trend in ameliorating T2DM via ameliorating pancreatic structure and function, and activating Akt/AMPK/GLUT4 signaling pathways. Conclusion This study indicated that the contents of main compounds were generally higher in CR TD than CR DG originated from the same raw materials. Additionally, changes in the contents of the primary components validated that the compound interactions are exclusive to SC TD during co-decoction, rather than SC DG. The disparate prossing of SC DG and SC TD caused differences both in chemical composition and hypoglycemic effect, suggesting that the substitutability of DG and TD requires further research.

Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remain largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. PRMT5 was identified as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. PRMT5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that PRMT5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, mice were treated with middle cerebral artery occlusion with the PRMT5 inhibitor EPZ015666 and found that PRMT5 inhibition sustains protection against neuronal death in vivo. Together, these findings revealed a novel epigenetic mechanism of PRMT5 in cerebral ischemia and uncovered a potential target for neuroprotection.

Abstract The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

Summary: Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC.

IntroductionPulmonary fibrosis is a terminal lung disease characterized by fibroblast proliferation, extracellular matrix accumulation, inflammatory damage, and tissue structure destruction. The pathogenesis of this disease, particularly idiopathic pulmonary fibrosis (IPF), remains unknown. Macrophages play major roles in organ fibrosis diseases, including pulmonary fibrosis. The phenotype and polarization of macrophages are closely associated with pulmonary fibrosis. A new direction in research on anti-pulmonary fibrosis is focused on developing drugs that maintain the stability of the pulmonary microenvironment.MethodsWe obtained gene sequencing data and clinical information for patients with IPF from the GEO datasets GSE110147, GSE15197, GSE24988, GSE31934, GSE32537, GSE35145, GSE53845, GSE49072, GSE70864, and GSE90010. We performed GO, KEGG enrichment analysis and GSEA analysis, and conducted weighted gene co-expression network analysis. In addition, we performed proteomic analysis of mouse lung tissue. To verify the results of bioinformatics analysis and proteomic analysis, mice were induced by intratracheal instillation of bleomycin (BLM), and gavaged for 14 days after modeling. Respiratory function of mice in different groups was measured. Lung tissues were retained for histopathological examination, Western Blot and real-time quantitative PCR, etc. In addition, lipopolysaccharide, interferon-γ and interleukin-4 were used to induce RAW264.7 cells for 12h in vitro to establish macrophage inflammation and polarization model. At the same time, HG2 intervention was given. The phenotype transformation and cytokine secretion of macrophages were investigated by Western Blot, RT-qPCR and flow cytometry, etc.ResultsThrough bioinformatics analysis and experiments involving bleomycin-induced pulmonary fibrosis in mice, we confirmed the importance of macrophage polarization in IPF. The analysis revealed that macrophage polarization in IPF involves a change in the phenotypic spectrum. Furthermore, experiments demonstrated high expression of M2-type macrophage-associated biomarkers and inducible nitric oxide synthase, thus indicating an imbalance in M1/M2 polarization of pulmonary macrophages in mice with pulmonary fibrosis.DiscussionOur investigation revealed that the ethyl acetate extract (HG2) obtained from the roots of Prismatomeris connata Y. Z. Ruan exhibits therapeutic efficacy against bleomycin-induced pulmonary fibrosis. HG2 modulates macrophage polarization, alterations in the TGF-β/Smad pathway, and downstream protein expression in the context of pulmonary fibrosis. On the basis of our findings, we believe that HG2 has potential as a novel traditional Chinese medicine component for treating pulmonary fibrosis.

Abstract Background The IQ-SPECT system is equipped with multifocal collimators and uses ordered-subset conjugate gradient minimization (OSCGM) as its reconstruction algorithm, achieving a shorter acquisition time than conventional SPECT. Left ventricular ejection fraction (LVEF) is overestimated by conventional SPECT in patients with small heart size. In this study, we compared IQ-SPECT with conventional SPECT and cardiovascular magnetic resonance (CMR) for the estimation of LVEF in patients with small hearts (males: EDV ≤ 60 ml, ESV ≤ 25 ml; females: EDV ≤ 45 ml, ESV ≤ 20 ml). Methods The study consisted of 49 consecutive patients (20 normal and 29 with small heart size) undergoing gated myocardial perfusion imaging (GMPI) with a 99mTc-labelled agent during stress or rest to assess the risk of coronary artery disease (CAD). The data were reconstructed using filtered back-projection (FBP) for conventional SPECT and OSCGM for IQ-SPECT. ESV, EDV, and LVEF were calculated using quantitative gated SPECT (QGS). To determine the optimal ordered-subset reconstruction parameters, we compared the LVEF from SPECT to the corresponding measurement from CMR. Results EDV, ESV, and LVEF values obtained from IQ-SPECT and conventional SPECT showed that the results of these two forms of SPECT were significantly correlated, although the EDV and ESV obtained by IQ-SPECT were higher than those obtained by conventional SPECT. IQ-SPECT yielded lower LVEF measurements than conventional SPECT (normal heart size: 50.6 ± 4.3% vs. 73.4 ± 8.4%, P = 0.002; small heart size: 62.1 ± 7.8% vs. 75.0 ± 11.4%, P 0.05; small heart size: 62.1 ± 7.8% vs. 64.6 ± 8.8%, P > 0.05). Five subsets (S) and 12 iterations (I) did not differ significantly in LVEF between CMR and IQ-SPECT for patients with small hearts (64.6 ± 8.8% vs. 62.1 ± 7.8%, P = 0.120), while 3 S and 10 I were the best parameters for patients with normal heart size (50.6 ± 4.3% vs. 53.1 ± 5.8%, P = 0.117). Conclusion With CMR as the standard, IQ-SPECT yields more reliable LVEF values than conventional SPECT for populations with small heart size. The best reconstruction parameters from IQ-SPECT were 5 S and 12 I for patients with small hearts.

Abstract Background Gastric cancer (GC) is a major cancer burden throughout the world with a high mortality rate. The performance of current predictive and prognostic factors is still limited. Integrated analysis is required for accurate cancer progression predictive biomarker and prognostic biomarkers that help to guide therapy. Methods An AI-assisted bioinformatics method that combines transcriptomic data and microRNA regulations were used to identify a key miRNA-mediated network module in GC progression. To reveal the module’s function, we performed the gene expression analysis in 20 clinical samples by qRT-PCR, prognosis analysis by multi-variable Cox regression model, progression prediction by support vector machine, and in vitro studies to elaborate the roles in GC cells migration and invasion. Results A robust microRNA regulated network module was identified to characterize GC progression, which consisted of seven miR-200/183 family members, five mRNAs and two long non-coding RNAs H19 and CLLU1. Their expression patterns and expression correlation patterns were consistent in public dataset and our cohort. Our findings suggest a two-fold biological potential of the module: GC patients with high-risk score exhibited a poor prognosis (p-value

The dynamic loading of CoCrNiSi0.3 medium-entropy alloys was performed by using Split Hopkinson Pressure Bar. The compression properties at different strain rates were investigated, and found to be sensitive to strain rates and have obvious strain rate strengthening effect. Under quasi-static compression (strain rate 10-4 s-1), the strain rate sensitivity m is 0.13, while under dynamic compression (strain rate 5 150 s-1) m 0.25. The shear properties of the alloy were studied through hat shaped shear test. The results show that the quasi-static shear yield strength is 330 MPa and the dynamic shear yield strength is 630 MPa. With the increase of the width of the reserved shear region, the peak stress decreases, but the shear failure strain increases obviously. When the width of the reserved shear region is 50 μm, the shear strain is as high as 12.8. Through the shear “freezing” experiment, the effect of increasing shear deformation on the grain microstructure and texture evolution of the material was studied. The results show that the geometric dislocation density in the grain increases with the increase of deformation, and the deformation texture evolves to A and P type texture, while the Cu type texture decreases gradually. Before the formation of adiabatic shear band, the temperature rise calculated by power-heat conversion lacks accuracy, which proves that the formation of adiabatic shear band is not caused by thermal softening.

Abstract Background Iris lactea var. chinensis, a perennial herbaceous species, is widely distributed and has good drought tolerance traits. However, there is little information in public databases concerning this herb, so it is difficult to understand the mechanism underlying its drought tolerance. Results In this study, we used Illumina sequencing technology to conduct an RNA sequencing (RNA-seq) analysis of I. lactea var. chinensis plants under water-stressed conditions and rehydration to explore the potential mechanisms involved in plant drought tolerance. The resulting de novo assembled transcriptome revealed 126,979 unigenes, of which 44,247 were successfully annotated. Among these, 1187 differentially expressed genes (DEGs) were identified from a comparison of the water-stressed treatment and the control (CK) treatment (T/CK); there were 481 upregulated genes and 706 downregulated genes. Additionally, 275 DEGs were identified in the comparison of the rehydration treatment and the water-stressed treatment (R/T). Based on Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) analysis, the expression levels of eight randomly selected unigenes were consistent with the transcriptomic data under water-stressed and rehydration treatment, as well as in the CK. According to Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, proline metabolism-related DEGs, including those involved in the ‘proline catabolic process’, the ‘proline metabolic process’, and ‘arginine and proline metabolism’, may play important roles in plant drought tolerance. Additionally, these DEGs encoded 43 transcription factors (TFs), 46 transporters, and 22 reactive oxygen species (ROS)-scavenging system-related proteins. Biochemical analysis and histochemical detection showed that proline and ROS were accumulated under water-stressed conditions, which is consistent with the result of the transcriptomic analysis. Conclusions In summary, our transcriptomic data revealed that the drought tolerance of I. lactea var. chinensis depends on proline metabolism, the action of TFs and transporters, and a strong ROS-scavenging system. The related genes found in this study could help us understand the mechanisms underlying the drought tolerance of I. lactea var. chinensis.

In the human genome, 98% of genes can be transcribed into non-coding RNAs (ncRNAs), among which lncRNAs and their encoded peptides play important roles in regulating various aspects of cellular processes and may serve as crucial factors in modulating the biological effects induced by ionizing radiation and microgravity. Unfortunately, there are few reports in space radiation biology on lncRNA-encoded peptides below 10kD due to limitations in detection techniques. To fill this gap, we integrated a variety of methods based on genomics and peptidomics, and discovered 22 lncRNA-encoded small peptides that are sensitive to space radiation and microgravity, which have never been reported before. We concurrently validated the transmembrane helix, subcellular localization, and biological function of these small peptides using bioinformatics and molecular biology techniques. More importantly, we found that these small peptides function independently of the lncRNAs that encode them. Our findings have uncovered a previously unknown human proteome encoded by 'non-coding' genes in response to space conditions and elucidated their involvement in biological processes, providing valuable strategies for individual protection mechanisms for astronauts who carry out deep space exploration missions in space radiation environments.

Macroscopic mechanical response and microstructure evolution of 7075-T6 aluminum alloy during dynamic compression were investigated by experiments and crystal plastic finite element method (CPFEM). The dynamic compression experiment of 7075-T6 aluminum alloy with a strain rate of 2 000 s-1 was carried out with a split Hopkinson pressure bar (SHPB). The microstructure of aluminum before and after dynamic compression was characterized by electron backscattering diffraction technique (EBSD). The internal state variables of dislocation density were introduced into the CPFEM model by modifying the strengthening model and the flow criterion. The effects of friction coefficient, dislocation multiplication coefficient, and dislocation annihilation coefficient on the macro mechanical properties of the specimens were investigated. The results show that the increase of dislocation multiplication coefficient aggravates the hardening behavior and increases the ultimate strength of the material, and the increase of dislocation annihilation coefficient reduces the ultimate strength of the material while weakens its hardening behavior. Through the comparison of experimental and simulation results, it could be seen that CPFEM accurately predicts the variation trend of the texture during dynamic compression, as more brass {110} texture and Goss {110} texture are generated.

BackgroundAnaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment.Case presentationThe adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023.ConclusionTaken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment.Trial registration numberNCT04767308.

BackgroundIdentification of new clinical markers contributes to a better understanding of the pathogenesis of asthma. Considering the crucial role of LIGHT in asthma, it may become a potential target for asthma. The aim of current study was to determine if circulating microRNAs (miRNAs) targeting LIGHT may be used as diagnostic biomarkers to distinguish asthma.MethodsBlood serum from a cohort of 60 subjects, including 20 cases with mild asthma, 20 cases with moderate-to-severe asthma, and 20 healthy controls were included. Serum was analyzed for circulating miRNAs profiles through miRNAs microarray. Real Time PCR was conducted to verify the results of miRNA microarray. Correlations between circulating miRNAs targeting LIGHT and clinical characteristics were investigated.ResultsA total of 365 miRNAs were differentially expressed in asthma patients. Among them, miR-107 and miR-140-5p were found to target LIGHT, and varied in asthmatics. Additionally, miR-107 and miR-140-5p expressions were positively correlated with the absolute value of peripheral eosinophils. Finally, miR-140-5p and miR-107 were demonstrated to have good diagnostic efficacy for asthma (AUC= 0.8667 and 0.9400) with good sensitivity (0.8000 and 0.8667,respectively) and specificity (0.8667 and 0.867). Thus, circulating miRNAs expressed differentially between healthy control and asthma patients.ConclusionPlasma miR-140-5p and miR-107 can be used as diagnostic biomarkers to distinguish patients with asthma from healthy control, and may take part in asthma pathogenesis by negatively regulating LIGHT. Further research was needed to evaluate their roles as potential biomarkers in the diagnosis of asthma.

Zinc oxide (ZnO) is an attractive material for gas sensors, and various ZnO-based sensors have been developed to detect gas pollution. In this work, a series of SiC/ZnO composites were fabricated by incorporating silicon carbide nanocrystals (SiC NCs) into ZnO microspheres by a grinding method. The SiC/ZnO composite exhibited a significantly enhanced gas sensitivity response toward NO gas in comparison to ZnO. The test revealed that the response of the composite was 251.1 for 100 ppm of nitrogen monoxide (NO), and the detection limit was as low as 100 ppb. Through spectral and comparative analyses, it has been indicated that the active functional groups of the SiC NCs have a substantial impact on the detection of NO, and the corresponding mechanism is studied and discussed. This work offers a simple strategy for the fabrication of SiC/ZnO material with enhanced sensitivity in sensing applications.

In the present study, the performance of a creative poly-generation plant generating electricity and freshwater was energetically, exegetically, economically, and environmentally analyzed. The system consists of a gas turbine as the prime mover and Kalina and humidification-dehumidification desalination units for waste heat recovery purposes. A sensitivity analysis was conducted to evaluate the influence of design parameters variation on the proposed system performance. The construction feasibility of the proposed system was assessed by utilizing Net Present Value and the payback period. According to the obtained data from the base simulation conditions, the total gained output ratio, exergetic efficiency, the total cost of products, Levelized total emission, and freshwater production capacity were obtained 0.9574, 43.05%, 20.22$/GJ, 63679kg/kW, and 10.77kg/s. The combustion chamber has the highest exergy destruction rate by 16382kW. Moreover, the sensitivity analysis revealed that an increase in the combustion temperature reduces pollutant emission and enhances the power generation rate and exergy efficiency. Regarding 2.5$/GJ and 0.085$/kWh as the fuel cost and electricity price, a total profit of 18.93$M at the end of economic book life can be obtained, with a payback time of 6.39years, demonstrating the feasibility of the plant for establishment.

Abstract Purpose We aimed to investigate the effect and significance of the rotation method with variable-angle anterior probe corrected for the depth of two kidneys on the determination of glomerular filtration rate (GFR) in total and single kidneys by the renal dynamic imaging Gates method. Methods Seventy-two patients who underwent dynamic renal imaging by the rotation method and abdominal CT in our hospital were collected in the present study. CT scanning, rotation method, Tonnesen's formula, and Li-Qian's formula were compared in terms of the depth of two kidneys, the depth difference between the two kidneys, and the total renal and single GFR obtained by substituting the renal depth values into Gates' formula. Results ①The depth of kidneys and GFR: Compared to CT, Tonnesen's formula significantly underestimated the depth of both kidneys and the total and single renal GFR (P 0.05), with a strong agreement and with the least bias in the values measured by the rotation method. ②Renal depth difference: Compared to CT, Tonnesen's formula and Li-Qian's formula underestimated the difference in depth between the two kidneys (P 0.05). The depth difference was positively correlated with the resulting changes in single renal function (|R(CT)-R(Li-Qian)|) and (|R(Rotation)-R(Li-Qian)|) (r = 0.881, 0.641, P

Summary: WNK1 is an important regulator in many physiological functions, yet its role in male reproduction is unexplored. In the male germline, WNK1 is upregulated in preleptotene spermatocytes indicating possible function(s) in spermatogenic meiosis. Indeed, deletion of Wnk1 in mid-pachytene spermatocytes using the Wnt7a-Cre mouse led to male sterility which resembled non-obstructive azoospermia in humans, where germ cells failed to complete spermatogenesis and produced no sperm. Mechanistically, we found elevated MTOR expression and signaling in the Wnk1-depleted spermatocytes. As MTOR is a central mediator of translation, we speculated that translation may be accelerated in these spermatocytes. Supporting this, we found the acrosome protein, ACRBP to be prematurely expressed in the spermatocytes with Wnk1 deletion. Our study uncovered an MTOR-regulating factor in the male germline with potential implications in translation, and future studies will aim to understand how WNK1 regulates MTOR activity and impact translation on a broader spectrum.

Summary: Current biochemical approaches have only identified the most well-characterized kinases for a tiny fraction of the phosphoproteome, and the functional assignments of phosphosites are almost negligible. Herein, we analyze the substrate preference catalyzed by a specific kinase and present a novel integrated deep neural network model named FuncPhos-SEQ for functional assignment of human proteome-level phosphosites. FuncPhos-SEQ incorporates phosphosite motif information from a protein sequence using multiple convolutional neural network (CNN) channels and network features from protein-protein interactions (PPIs) using network embedding and deep neural network (DNN) channels. These concatenated features are jointly fed into a heterogeneous feature network to prioritize functional phosphosites. Combined with a series of in vitro and cellular biochemical assays, we confirm that NADK-S48/50 phosphorylation could activate its enzymatic activity. In addition, ERK1/2 are discovered as the primary kinases responsible for NADK-S48/50 phosphorylation. Moreover, FuncPhos-SEQ is developed as an online server.

Abstract Mouse embryonic stem cells (mESCs) cycle in and out of a transient 2-cell (2C)-like totipotent state, driven by a complex genetic circuit involves both the coding and repetitive sections of the genome. While a vast array of regulators, including the multi-functional protein Rif1, has been reported to influence the switch of fate potential, how they act in concert to achieve this cellular plasticity remains elusive. Here, by modularizing the known totipotency regulatory factors, we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repressive complex PRC1.6. Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs. The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6, bolstering the intactness of the PRC1.6 complex. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state. Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352, but also derepresses a group of the endogenous retroviral element MERVL, a key marker for totipotency. Collectively, our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential, shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.

ABSTRACTVitrimer is a new type of material that combine the advantages of thermoplastic and thermoset materials. The rapid dynamic exchange reactions at high temperature allow the topology of cross-linked networks to change and rearrange while keeping material structures and properties intact. The concept of vitrimer has emerged to provide a viable strategy for the recycling of high-performance polymer materials, and lots of research works have been carried out for the development of various types of vitrimers. In addition, the recycling strategies for vitrimers are particularly important to determine the performance and potential applications of the recovered materials. Therefore, it is an innovative and valuable perspective to discuss vitrimer materials according to their different recycling strategies. In this review, we start with a brief overview of vitrimers, and then, focus on recycling strategies for vitrimers. Specifically, we highlight the advantages and disadvantages of the two different recycling strategies: physical and chemical recycling methods, and then explore the feasibility of upcycling vitrimers using 3D printing technology. Finally, the impact of recycling strategies on vitrimer materials and the prospects for maximizing the use of vitrimer materials are discussed.

Nucleic acid therapeutics, which involve transferring exogenous genes inside target cells, are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level. Ideally, this kind of treatment modality will not lead to an unwanted immune response. Compared with traditional treatment methods, nucleic acid therapeutics can achieve prolonged and stable curative effects. As an emerging treatment method, nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions, including infectious diseases, cancer, immune-related diseases, and monogenetic diseases. To date, a large number of clinical trials have been conducted, and more than 30 nucleic acid drugs have been approved, highlighting the strong potential of this approach in clinical practice. Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately. However, some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver. Therefore, biosafety assessment of delivery systems before their application in clinical settings is critical. In this review, we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies, with particular focus on the carriers themselves, drug administration method, and overall treatment of the disease.

The relationship between paleogeographic pattern and sedimentary differentiation of evaporite-carbonate symbiotic system is examined based on logging, core and thin section data, by taking the sixth sub-member of fifth member of Ordovician Majiagou Formation (M56) in the central-eastern Ordos Basin as an example. (1) Seven sub-geomorphic units (Taolimiao west low, Taolimiao underwater high, Taolimiao east low, Hengshan high, East salt low, North slope and Southwest slope) developed in the study area. (2) The “three lows” from west to east developed dolomitic restricted lagoon, evaporite evaporative lagoon and salt evaporative lagoon sedimentary facies respectively, the “two highs” developed high-energy grain beach and microbial mound, and the north and south slopes developed dolomitic flats around land. (3) The paleogeographic pattern caused natural differentiation of replenishment seawater from the northwest Qilian sea, leading to the eccentric sedimentary differentiation of dolomite, evaporite and salt rock symbiotic system from west to east, which is different from the classic “bull's eye” and “tear drop” distribution patterns. (4) As the Middle Qilian block subducted and collided into the North China Plate, the far-end compression stress transferred, giving rise to the alternate highland and lowland in near north to south direction during the sedimentary period of M56 sub-member. (5) Taolimiao underwater high and Hengshan high developed favorable zones of microbial mounds and grain shoals in south to north strike in M56 sub-member, making them favorable exploration areas with great exploration potential in the future.

Abstract Stem cell-based embryo models present new opportunities to study early embryonic development. In a recent study, Kagawa et al. identified an approach to create human pluripotent stem cell-based blastoids that resemble the human blastocysts. These blastoids efficiently generated analogs of the EPI, TE, PrE lineages with transcriptomes highly similar to those found in vivo. Furthermore, the formation of these lineages followed the same sequence and pace of blastocyst development, and was also dependent on the same pathways required for lineage specification. Finally, the blastoids were capable of attaching to stimulated endometrial cells to mimic the process of implantation. While more comprehensive analysis is needed to confirm its validity and usefulness, this new blastoid system presents the latest development in the attempt to model early human embryogenesis in vitro.

Background Tea plantations support regional sustainable development and have the potential to support more biodiversity than urban open spaces. Numerous studies have shown the value of low-intensity agroecosystems for preserving biodiversity, however tea plantations have received less attention. The relationship between tea plantations and the diversity of macro-organisms, such as birds, is still not fully understood. Methods We investigated the bird diversity and vegetation conditions and calculated landscape metrics in 30 tea plantations in Anji County, Zhejiang Province, China. At these 30 sampling sites, we recorded 262 individuals belonging to 37 species, which were classified into two guilds: nature- and urban-dependent birds. We used cluster analysis to group the sampling sites based on the abundance of the birds. Then we evaluated the effects of associated plant diversity in tea plantations and the surrounding landscape composition on these bird guilds using species association computation and a generalized linear model. Results The results show that the maintenance of bird diversity by tea plantations benefits both nature- and urban-dependent birds. We found that landscape-scale factors surrounding the tea plantations mainly affected the bird richness due to their habitat selection. Landscape agglomeration and habitat quality were the dominant landscape-scale metrics. Patch-scale factors of tea plantations, especially the vegetation structure, had a strong influence on the abundance of the birds. Nature-dependent birds preferred to occur in tea plantations with perennial herbs, while urban-dependent birds were attracted by the general distributed plants, as annual herbs. Therefore, we concluded that tea plantations play an important role as a transitional zone between natural habitats and urban areas, thus reducing the impact of urbanization and maintaining bird diversity in low-quality habitats.

In the marine engineering industry, turbocharged diesel engines are often used to generate electricity, and hot oil can be extracted after generating electricity. However, marine diesel engine heat recovery can be distinguished from gas heat recovery for turbocharged and nonturbocharged diesel engine systems. The ideal air model Brayton cycle is used to evaluate the feasibility of turbocharged/nonturbocharged cogeneration retrofits in turbocharged diesel engine systems, and the paper is designed to evaluate the effect of pressure and temperature and cooling ratio of exergy efficiency. The results show that the performance of turbocharged and nonturbocharged work increases with increasing pressure ratio until it reaches a maximum value and decreases with increasing pressure ratio at a constant temperature. If an electric generator is selected first, the heat recovery after the turbocharger can be used to improve the contract for heating and electricity needs. While the exergy efficiency is selected priorly, cogeneration retrofit for heating and electricity demands can be used for heat recovery without the turbocharger system.

Although pressure pipelines serve as a secure and energy-efficient means of transporting oil, gas, and chemicals, they are susceptible to fatigue cracks over extended periods of cyclic loading due to the challenging operational conditions. Their quality and efficiency directly affect the safe operation of the project. Therefore, a thorough and precise characterization approach towards pressure pipelines can proactively mitigate safety risks and yield substantial economic and societal benefits. At present, the current mainstream 2D ultrasound imaging technology faces challenges in fully visualizing the internal defects and topography of pressure pipelines. Reverse time migration (RTM), widely employed in geophysical exploration, has the capability to visualize intricate geological structures. In this paper, we introduced the RTM into the realm of ultrasonic non-destructive testing, and proposed a 3D ultrasonic RTM imaging method for internal defects and sensor settings of pressure pipelines. To accurately simulate the extrapolation of wave field in 3D pressure pipelines, we set the absorbing boundary and double free boundary in cylindrical coordinates. Subsequently, using the 3D ultrasonic RTM approach, we attained higher-precision 3D imaging of internal defects in the pressure pipelines through suppressing imaging artifacts. By comparing and analyzing the imaging results of different sensor settings, the design of the observation system is optimized to provide a basis for the imaging and interpretation of actual data. Both simulations and actual field data demonstrate that our approach delivers top-notch 3D imaging of pipeline defects (with an imaging range accuracy up to 97.85%). This method takes into consideration the complexities of multiple scattering and mode conversions occurring at the base of the defects as well as the optimal sensor settings.

To address the problem that the energy response of the plastic scintillator detector is very low in the low energy range, this paper proposes a method to optimize the energy response characteristics by combining the CaWO4 energy compensation layer and the genetic algorithm. First, the energy deposition of X/γ rays in a plastic scintillator with a CaWO4 energy compensation layer is modeled and simulated using MCNP software; then, the thickness and hollow radius of the compensation layer are optimized by using genetic algorithm to run this simulation program. The results show that after adding a CaWO4 compensation layer with a thickness of 45 µm and a hollow radius of 1 cm at the front of the plastic scintillator, its energy response characteristics are consistent in the range of 50 keV to 1.5 MeV, which meets the requirement of IEC 61584:2001 for the energy response coefficient less than ±30%. The maximum deviation of the energy response coefficient at the energy point of 0.662 MeV is reduced from 44% to 13%.

BackgroundThe CAR T-cell therapy is a promising approach to treating hematologic malignancies. However, the application in solid tumors still has many tough challenges, including heterogenicity in antigen expressions and immunosuppressive tumor microenvironment (TME). As a new cancer treatment modality, oncolytic virotherapy can be engineered to circumvent these obstacles for CAR T cell therapy in solid tumors.MethodsIn this study, an oHSV T7011 is engineered to drive ectopic expression of dual-antigens, extracellular domains of CD19 and BCMA, on the solid tumor cell surface to be targeted by approved CAR T cells. In addition, multiple immunomodulators, CCL5, IL-12, and anti-PD-1 antibody are also included to modulate the TME. The antitumor activities of T7011 in combination with CD19 or BCMA CAR T-cell were evaluated in vitro and in vivo.ResultsThe expression of CD19 or BMCA on the tumor cell surface could be detected after T7011 infection. The level of CCL5 in TME was also increased. Efficacy studies demonstrated that combination with T7011 and CAR-TCD19 or CAR-TBCMA cells showed significant synergistic anti-tumor responses in several solid tumor models.ConclusionThese studies indicated that the new generation of oHSV T7011 can be a promising combinational therapy with CD19 or BCMA-specific CAR T cells for the treatment of a broad range of solid tumors.

Abstract Background Research shows that nano-bioceramics can modulate the differentiation of dental stem cells. The novel ready-to-use calcium-silicate-based root-canal sealer iRoot SP is widely used in root filling. Accordingly, the aim of this study was to evaluate the effects of iRoot SP on proliferation and osteogenic differentiation in human stem cells from the apical papilla (hSCAPs). Methods hSCAPs were isolated and characterized in vitro, then cultured with various concentrations of iRoot SP extract. Cell proliferation was assessed by CCK-8 assay, and scratch-wound-healing assays were performed to evaluate cell-migration capacity. hSCAPs were then cultured in osteogenic medium supplemented with iRoot SP extracts. Alkaline phosphatase (ALP) activity assay was used to evaluate ALP enzyme levels. Alizarin red staining and cetylpyridinium chloride (CPC) assays were performed to assess calcified-nodule formation and matrix-calcium accumulation of hSCAPs. The mRNA and protein expression levels of the osteogenic markers OCN, OSX, Runx2, and DSPP were determined by qRT-PCR and Western blotting. The data were analyzed using one-way ANOVA and LSD-t tests. Results iRoot SP at low concentrations (2, 0.2, and 0.02 mg/mL) is nontoxic to hSCAPs. iRoot SP at concentrations of 0.02 and 0.2 mg/mL significantly increases cell-migration capacity. In terms of osteogenic differentiation, 0.2 mg/mL iRoot SP promotes intracellular ALP activity and the formation of mineralized nodules. Moreover, the expression of osteogenic markers at the mRNA and protein levels are upregulated by iRoot SP. Conclusion iRoot SP is an effective filling material for periapical bone regeneration.

Accurate prediction of urban residential rents is of great importance for landlords, tenants, and investors. However, existing rents prediction models face challenges in meeting practical demands due to their limited perspectives and inadequate prediction performance. The existing individual prediction models often lack satisfactory accuracy, while ensemble learning models that combine multiple individual models to improve prediction results often overlook the impact of spatial heterogeneity on residential rents. To address these issues, this paper proposes a novel prediction model called GERPM, which stands for Geographically Weighted Stacking Ensemble Learning-Based Urban Residential Rents Prediction Model. GERPM comprehensively analyzes the influencing factors of residential rents from multiple perspectives and leverages a geographically weighted stacking ensemble learning approach. The model combines multiple machine learning and deep learning models, optimizes parameters to achieve optimal predictions, and incorporates the geographically weighted regression (GWR) model to consider spatial heterogeneity. By combining the strengths of deep learning and machine learning models and taking into account geographical factors, GERPM aims to improve prediction accuracy and provide robust predictions for urban residential rents. The model is evaluated using housing data from Nanjing, a major city in China, and compared with representative individual prediction models, the equal weight combination model, and the ensemble learning model. The experimental results demonstrate that GERPM outperforms other models in terms of prediction performance. Furthermore, the model’s effectiveness and robustness are validated by applying it to other major cities in China, such as Shanghai and Hangzhou. Overall, GERPM shows promising potential in accurately predicting urban residential rents and contributing to the advancement of the rental market.

Benefiting from the advantages like large surface area, flexible constitution, and diverse structure, metal-organic frameworks (MOFs) have been one of the most ideal candidates for nanozymes. In this study, a nitro-functionalized MOF, namely NO2-MIL-53(Cu), was synthesized. Multi-enzyme mimetic activities were discovered on this MOF, including peroxidase-like, oxidase-like, and laccase-like activity. Compared to the non-functional counterpart (MIL-53(Cu)), NO2-MIL-53(Cu) displayed superior enzyme mimetic activities, indicating a positive role of the nitro group in the MOF. Subsequently, the effects of reaction conditions on enzyme mimetic activities were investigated. Remarkably, NO2-MIL-53(Cu) exhibited excellent peroxidase-like activity even at neutral pH. Based on this finding, a simple colorimetric sensing platform was developed for the detection of H2O2 and glucose, respectively. The detection liner range for H2O2 is 1–800 μM with a detection limit of 0.69 μM. The detection liner range for glucose is linear range 0.5–300 μM with a detection limit of 2.6 μM. Therefore, this work not only provides an applicable colorimetric platform for glucose detection in a physiological environment, but also offers guidance for the rational design of efficient nanozymes with multi-enzyme mimetic activities.

Two-phase flow, especially gas-liquid two-phase flow, has a wide application in industrial field. The diagnosis of two-phase flow parameters, which directly determine the flow and heat transfer characteristics, plays an important role in providing the design reference and ensuring the security of online operation of two-phase flow system. Computer tomography (CT) is a good way to diagnose such parameters with imaging method. This paper has proposed a novel image reconstruction method for thermal neutron CT of two-phase flow with improved simulated annealing (ISA) algorithm, which makes full use of the prior information of two-phase flow and the advantage of stochastic searching algorithm. The reconstruction results demonstrate that its reconstruction accuracy is much higher than that of the reconstruction algorithm based on weighted total difference minimization with soft-threshold filtering (WTDM-STF). The proposed method can also be applied to other types of two-phase flow CT modalities (such as X(γ)-ray, capacitance, resistance and ultrasound).

Cellular energy metabolism plays a crucial role in the regulation of macrophage polarization and in the execution of immune functions. A recent study showed that Slc6a8-mediated creatine uptake from exogenous supplementation modulates macrophage polarization, yet little is known about the role of the de novo creatine de novobiosynthesis pathway in macrophage polarization. Here, we observed that glycine amidinotransferase (GATM), the rate-limiting enzyme for creatine synthesis, was upregulated in alternative (M2) polarized macrophages, and was dependent on the transcriptional factor STAT6, whereas GATM expression was suppressed in the classical polarized (M1) macrophage. Next, we revealed that exogenous creatine supplementation enhanced IL-4-induced M2 polarization, confirming recent work. Furthermore, we revealed that genetic ablation of GATM did not affect expression of M1 marker genes (Nos2, IL1b, IL12b) or the production of nitric oxide in both peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs). By contrast, expression levels of M2 markers (Arg1, Mrc1, Ccl17 and Retnla) were lower following GATM deletion. Moreover, we found that deletion of GATM in resident alveolar macrophages (AMs) significantly blocked M2 polarization but with no obvious effect on the number of cells in knockout mice. Lastly, an upregulation of GATM was found in lung tissue and bronchoalveolar lavage fluid macrophages from HDM-induced asthmatic mice. Our study uncovers a previously uncharacterized role for the de novo creatine biosynthesis enzyme GATM in M2 macrophage polarization, which may be involved in the pathogenesis of related inflammatory diseases such as an T helper 2 (Th2)-associated allergic asthma.