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Objective To investigate the efficacy of intravitreal injection of Ozurdex® in the treatment of refractory diabetic macular edema (DME) with different optical coherence tomography (OCT) patterns. Methods A total of 38 patients (41 eyes) who underwent fundus examination and were diagnosed with refractory DME in Department of Ophthalmology in our hospital from June 2018 to June 2020 were enrolled in this study, and according to the OCT pattern, they were divided into diffuse retinal thickening (DRT) group, cystoid macular edema (CME) group, and serous retinal detachment (SRD) group. Intravitreal injection of Ozurdex® was performed for all diseased eyes as needed, and best corrected visual acuity (BCVA) and OCT measurements were performed before treatment and at 1, 3, and 6 months after treatment. The three groups were compared in terms of BCVA, central foveal thickness (CFT), the integrity of external limiting membrane, ellipsoid zone integrity, and the number of hyperreflective dots (HRDs) before and after treatment. Results All three groups had a significant improvement in BCVA at 1, 3, and 6 months after treatment (Fintra-group=15.334-42.187,P0.05), and at 1, 3, and 6 months after treatment, there was a significant change in the proportion of diseased eyes with different numbers of HRDs (H=23.645-39.117,P

Objective: Reliably prediction models for coronary artery abnormalities (CAA) in children aged >5 years with Kawasaki disease (KD) are still lacking. This study aimed to develop a nomogram model for predicting CAA at 4 to 8 weeks of illness in children with KD older than 5 years. Methods: A total of 644 eligible children were randomly assigned to a training cohort (n = 450) and a validation cohort (n = 194). The least absolute shrinkage and selection operator (LASSO) analysis was used for optimal predictors selection, and multivariate logistic regression was used to develop a nomogram model based on the selected predictors. Area under the receiver operating characteristic curve (AUC), calibration curves, Hosmer-Lemeshow test, Brier score, and decision curve analysis (DCA) were used to assess model performance. Results: Neutrophil to lymphocyte ratio, intravenous immunoglobulin resistance, and maximum baseline z-score ≥ 2.5 were identified by LASSO as significant predictors. The model incorporating these variables showed good discrimination and calibration capacities in both training and validation cohorts. The AUC of the training cohort and validation cohort were 0.854 and 0.850, respectively. The DCA confirmed the clinical usefulness of the nomogram model. Conclusions: A novel nomogram model was established to accurately assess the risk of CAA at 4–8 weeks of onset among KD children older than 5 years, which may aid clinical decision-making.

Liver transplantation (LT) is the standard therapy for individuals afflicted with end-stage liver disease. Despite notable advancements in LT technology, the incidence of early allograft dysfunction (EAD) remains a critical concern, exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients. Unfortunately, the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD. Herein, we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients, with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages. Comparison of the 75 231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells, granzyme B+ (GZMB+) granzyme K+ (GZMK+) natural killer cells, and S100 calcium binding protein A12+ (S100A12+) neutrophils. Moreover, we verified this immune niche and its association with EAD occurrence in two independent cohorts. Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level, thus, offering valuable insights into EAD onset.

Abstract Background This case report documents a case of malignant pheochromocytoma manifested as vision changes with lung metastasis and recurrence. Case presentation A 10-year-old Han Chinese girl presented with vision changes and was eventually diagnosed with pheochromocytoma by contrast-enhanced computed tomography, urine vanillylmandelic acid. After medication for hypertension and surgery, clinical symptoms disappeared. Malignant pheochromocytoma with lung metastasis was confirmed histologically using the Pheochromocytoma of the Adrenal Gland Scaled Score scoring system and genetically with succinate dehydrogenase complex iron sulfur subunit B mutation, and 3 months later, unplanned surgery was performed because of the high risks and signs of recurrence. She is asymptomatic as of the writing of this case report. Our patient’s case highlights the importance of considering a diagnosis of malignant pheochromocytoma, and long-term follow-up for possible recurrence. Conclusion Although there are well-recognized classic clinical manifestations associated with pheochromocytoma, atypical presentation, such as vision changes in children, should be considered. In addition, malignant pheochromocytoma children with a high Pheochromocytoma of the Adrenal Gland Scaled Score and succinate dehydrogenase complex iron sulfur subunit B mutation require a long-term follow-up or even unplanned surgery because of the higher risk of recurrence.

Hybrid multibend achromat (MBA) lattice with a pair of dispersion bumps separated by −I transformation is used in some diffraction-limited storage ring (DLSR) designs, which can obtain relatively large dynamic apertures. However, the −I transformation also largely restricts the horizontal tune of the lattice cell. In this paper, an MBA lattice with four dispersion bumps is proposed, which has relatively good flexibility in adjusting the number of bends in the lattice cell and the lattice cell tunes, while also achieving the effective sextupole cancellation within the lattice arc section. The new lattice can have a larger horizontal cell tune than the hybrid MBA lattice with the same number of bends, which is beneficial for reducing the emittance. In the new lattice, −I transformation is not necessary for the sextupole cancellation between paired bumps, and a general relation of sextupole cancellation is used. Following this lattice concept, a 7BA lattice is preliminarily designed for a 1.5 GeV DLSR. This lattice concept can also be extended to the case of MBA lattice with more bumps.

In this study, the surface flame retardancy of polycarbonate (PC) was improved and the impact of flame retardants on the substrate were minimized by pre-mixing Al _2 O _3 particles with dichloromethane, an infiltration promoter, to form a suspension, and then treating PC with the suspension to form an Al _2 O _3 infiltration layer. For this layer, its structure and composition were characterized, its flame retardancy was evaluated, and its flame retardancy mechanism was investigated. The characterization results confirmed that an Al _2 O _3 infiltration layer was successfully prepared on the PC surface under the aid of dichloromethane and that the involvement of dichloromethane induced certain microscopic pores and voids in the PC, with some dichloromethane remaining within the surface infiltration layer. The surface Al _2 O _3 infiltration layer mainly served as a condensed-phase flame retardant. The infiltration layer prepared using a suspension with a dichloromethane-to-Al _2 O _3 mass ratio of 24:1 not only exhibited a good overall performance but also achieved the best improvement in the PC flame retardancy, such as an increase in the vertical burning rating from HB to V-0, as well as the LOI increased from 24 to 31.3, and a 35% reduction in the peak heat release rate compared to those of pure PC.

Automatic modulation recognition (AMR) is widely employed in communication systems. However, under conditions of low signal-to-noise ratio (SNR), recent studies reveal limitations in achieving high AMR accuracy. In this work, we introduce a novel network architecture that leverages a transformer-inspired approach tailored for AMR, called Feature-Enhanced Transformer with skip-attention (FE-SKViT). This innovative design adeptly harnesses the advantages of translation variant convolution and the Transformer framework, handling intra-signal variance and small cross-signal variance to achieve enhanced recognition accuracy. Experimental results on RadioML2016.10a, RadioML2016.10b, and RML22 datasets demonstrate that the Feature-Enhanced Transformer with skip-attention (FE-SKViT) excels over other methods, particularly under low SNR conditions ranging from −4 to 6 dB.

Abstract The expression level of SLC35A3 is associated with the prognosis of many cancers, but its role in colorectal cancer (CRC) is unclear. The purpose of our study was to elucidate the role of SLC35A3 in CRC. The expression levels of SLC35A3 in CRC were evaluated through tumor immune resource assessment (TIMER), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), Human Protein Atlas (HPA), qRT-PCR, and immunohistochemical evaluation. TCGA, GEO, and ICGC databases were used to analyze the diagnostic and prognostic value of SLC35A3 in CRC. A overall survival (OS) model was constructed and validated based on the expression level of SLC35A3 and multivariable analysis results. The cBioPortal tool was used to analyze SLC35A3 mutation in CRC. The UALCAN tool was used to analyze the promoter methylation level of SLC35A3 in colorectal cancer. In addition, the role of SLC35A3 in CRC was determined through GO analysis, KEGG analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and immune checkpoint correlation analysis. In vitro experiments validated the function of SLC35A3 in colorectal cancer cells. Compared with adjacent normal tissues and colonic epithelial cells, the expression of SLC35A3 was decreased in CRC tissues and CRC cell lines. Low expression of SLC35A3 was associated with N stage, pathological stage, and lymphatic infiltration, and it was unfavorable for OS, disease-specific survival (DSS), recurrence-free survival (RFS), and post-progression survival (PPS). According to the Receiver Operating Characteristic (ROC) analysis, SLC35A3 is a potential important diagnostic biomarker for CRC patients. The nomograph based on the expression level of SLC35A3 showed a better predictive model for OS than single prognostic factors and TNM staging. SLC35A3 has multiple types of mutations in CRC, and its promoter methylation level is significantly decreased. GO and KEGG analysis indicated that SLC35A3 may be involved in transmembrane transport protein activity, cell communication, and interaction with neurotransmitter receptors. GSEA revealed that SLC35A3 may be involved in energy metabolism, DNA repair, and cancer pathways. In addition, SLC35A3 was closely related to immune cell infiltration and immune checkpoint expression. Immunohistochemistry confirmed the positive correlation between SLC35A3 and helper T cell infiltration. In vitro experiments showed that overexpression of SLC35A3 inhibited the proliferation and invasion capability of colorectal cancer cells and promoted apoptosis. The results of this study indicate that decreased expression of SLC35A3 is closely associated with poor prognosis and immune cell infiltration in colorectal cancer, and it can serve as a promising independent prognostic biomarker and potential therapeutic target.

Abstract Background Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that predominantly affects children, and no specific diagnostic biomarkers for KD are available. Platelet-derived growth factor CC (PDGF-CC) is a peptide with angiogenic properties that has been amply demonstrated to play a critical role in the cardiovascular system. This study aimed to investigate the serum expression of PDGF-CC in children with KD and to evaluate the ability of PDGF-CC to diagnose KD. Methods A total of 96 subjects, including 59 KD patients, 17 febrile controls (FC), and 20 healthy controls (HC), were enrolled. Serum levels of PDGF-CC were measured via enzyme-linked immunosorbent assay. The associations between PDGF-CC and clinical laboratory parameters were investigated by correlation analysis. The diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis. Results Serum PDGF-CC levels in the KD group were significantly higher than in the FC and HC groups. Serum PDGF-CC levels in the KD group were positively correlated with white blood cell counts, percentage of neutrophils, IL-2, IL-12p70, TNF-α, and IL-1β levels, and negatively correlated with the percentage of lymphocytes. In the analysis of ROC curves, the area under the curve was 0.796 (95% confidence interval 0.688–0.880; P

The Mediterranean diet (MD) had a protective effect on cancer prevention. However, there has not been a systematic evaluation of the diet's comprehensive effects on metabolic indices and quality of life in cancer patients. The present meta-analysis summarizes for the first time the effects of MD on metabolic indices and quality of life in cancer patients. We conducted a randomized controlled trial (RCT) search on PubMed, Embase, and Cochrane Library, which recruited cancer patients receiving the MD intervention. In this meta-analysis, nine RCTs were included. Two authors independently extracted the data and checked the accuracy of the results. Compared with the control group, MD reduced the body weight (p

Abstract Background Immune checkpoint inhibitors (ICIs) have altered the clinical management of non-small cell lung cancer (NSCLC). However, the low response rate, severe immune-related adverse events (irAEs), and hyperprogressive disease following ICIs monotherapy require attention. Combination therapy may overcome these limitations and traditional Chinese medicine with immunomodulatory effects provides a promising approach. Shenmai injection (SMI) is a clinically effective adjuvant treatment for cancer with chemotherapy and radiotherapy. Therefore, the combined effects and mechanisms of SMI and programmed death-1 (PD-1) inhibitor against NSCLC was focused on this study. Methods A Lewis lung carcinoma mouse model and a lung squamous cell carcinoma humanized mouse model were used to investigate the combined efficacy and safety of SMI and PD-1 inhibitor. The synergistic mechanisms of the combination therapy against NSCLC were explored using single-cell RNA sequencing. Validation experiments were performed using immunofluorescence analysis, in vitro experiment, and bulk transcriptomic datasets. Results In both models, combination therapy alleviated tumor growth and prolonged survival without increasing irAEs. The GZMA high and XCL1 high natural killer (NK) cell subclusters with cytotoxic and chemokine signatures increased in the combination therapy, while malignant cells from combination therapy were mainly in the apoptotic state, suggesting that mediating tumor cell apoptosis through NK cells is the main synergistic mechanisms of combination therapy. In vitro experiment confirmed that combination therapy increased secretion of Granzyme A by NK cells. Moreover, we discovered that PD-1 inhibitor and SMI combination blocked inhibitory receptors on NK and T cells and restores their antitumoral activity in NSCLC better than PD-1 inhibitor monotherapy, and immune and stromal cells exhibited a decrease of angiogenic features and attenuated cancer metabolism reprogramming in microenvironment of combination therapy. Conclusions This study demonstrated that SMI reprograms tumor immune microenvironment mainly by inducing NK cells infiltration and synergizes with PD-1 inhibitor against NSCLC, suggested that targeting NK cells may be an important strategy for combining with ICIs. Video Abstract

The effect of the modification treatment on the refinement of primary carbides and wear resistance of 35% Cr-4.0% C hypereutectic high chromium cast iron (HHCCI) was investigated using the first-principles calculations, XRD, SEM, TEM, hardness tests, and wear tests. The addition of N elements to HHCCI refined the size of the M7C3 primary carbide from 13.25 ± 0.72 μm to 11.67 ± 0.33 μm under the effect of adsorption refinement. When the compound modification elements (N + Ti + V + RE-Mg) were added, the combination of adsorption refinement and heterogeneous nucleation refinement significantly reduced the carbide size to 5.35 ± 0.15 μm. The refinement of the M7C3 primary carbide can be attributed to two components: 1) the refinement of the heterogeneous nucleation of TiC and VC. 2) the combination of N, Ti, and V with the M7C3 preferred growth surface (0001) resulting in the refinement by adsorption and reduce the size of the primary carbide. The hypereutectic high chromium cast iron after the compound modification exhibited excellent wear resistance. Under dry sliding wear condition, Compared with the unmodified sample, the wear resistance increased by 75%. Under corrosive wear conditions, the wear resistance is increased by 98.1%.

Introduction Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease with limited therapeutic options and high lethality, related to alveolar type II epithelial (ATII) cell dysregulation, the abnormal repair of alveolar epithelial cells and activation of fibroblasts promote the development of pulmonary fibrosis. Fatty acid binding protein 1 (FABP1) was significantly downregulated in the fibrotic state by proteomics screening in our previous date, and the ATII cell dysregulation can be mediated by FABP1 via regulating fatty acid metabolism and intracellular transport. The aim of this study was to evaluate the role and potential mechanism of FABP1 in the development of pulmonary fibrosis.Methods Proteomics screening was used to detect changes of the protein profiles in two different types (induced by bleomycin and silica, respectively) of pulmonary fibrosis models. The localisation of FABP1 in mouse lung was detected by Immunofluorescence and immunohistochemistry. Experimental methods such as lung pathology, micro-CT, western blotting, small animal imaging in vivo, EdU, etc were used to verify the role of FABP1 in pulmonary fibrosis.Results The expression of FABP1 in the mouse lung was significantly reduced in the model of pulmonary fibrosis from our proteomic analysis and immunological methods, the double immunofluorescence staining showed that FABP1 was mainly localised in type II alveolar epithelial cells. Additionally, the expression of FABP1 was negatively correlated with the progression of pulmonary fibrosis. Further in vivo and in vitro experiments showed that overexpression of FABP1 alleviated pulmonary fibrosis by protecting alveolar epithelium from injury and promoting cell survival.Conclusion Our findings provide a proof-of-principle that FABP1 may represent an effective treatment for pulmonary fibrosis by regulating alveolar epithelial regeneration, which may be associated with the fatty acid metabolism in ATII cells.

Panax ginseng (PG) and Panax notoginseng (PN) are highly valuable Chinese medicines (CM). Although both CMs have similar active constituents, their clinical applications are clearly different. Over the past decade, RNA sequencing (RNA-seq) analysis has been employed to investigate the molecular mechanisms of extracts or monomers. However, owing to the limited number of samples in standard RNA-seq, few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level. Here, we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq (TCM-seq), a high-throughput, low-cost workflow to molecularly evaluate CM perturbations. A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq. Transcriptomes from repeated samples were used to verify the robustness of TCM-seq. We then focused on the primary active components, Panax notoginseng saponins (PNS) and Panax ginseng saponins (PGS) extracted from PN and PG, respectively. We also characterized the transcriptome changes of 10 cell lines, treated with four different doses of PNS and PGS, using TCM-seq to compare the differences in their perturbing effects on genes, functional pathways, gene modules, and molecular networks. The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct. PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease, whereas PNS resulted in a greater coagulation effect on vascular endothelial cells. This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Abstract Tissues are highly complicated with spatial heterogeneity in gene expression. However, the cutting-edge single-cell RNA-seq technology eliminates the spatial information of individual cells, which contributes to the characterization of cell identities. Herein, we propose single-cell spatial position associated co-embeddings (scSpace), an integrative method to identify spatially variable cell subpopulations by reconstructing cells onto a pseudo-space with spatial transcriptome references (Visium, STARmap, Slide-seq, etc.). We benchmark scSpace with both simulated and biological datasets, and demonstrate that scSpace can accurately and robustly identify spatially variated cell subpopulations. When employed to reconstruct the spatial architectures of complex tissue such as the brain cortex, the small intestinal villus, the liver lobule, the kidney, the embryonic heart, and others, scSpace shows promising performance on revealing the pairwise cellular spatial association within single-cell data. The application of scSpace in melanoma and COVID-19 exhibits a broad prospect in the discovery of spatial therapeutic markers.

ObjectiveBazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC.MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD’s active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an “herb-ingredient-target” network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer.ResultsBZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the “herb-ingredient-target” network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles.ConclusionBZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations.

Current methods to reanalyze bulk RNA-seq at spatially resolved single-cell resolution have limitations. Here, the authors develop Bulk2Space, a spatial deconvolution algorithm using single-cell and spatial transcriptomics as references, providing new insights into spatial heterogeneity within bulk tissue.

Abstract Aim of the study We aimed to explore how weipiling (WPL) decoction WPL alleviates gastric precancerous lesions (GPLs) and uncover its anti-inflammatory roles in GPL treatment. Materials and methods The anti-GPL action mechanisms of WPL were analysed using a network pharmacological method. The WPL extract was prepared in a traditional way and evaluated for its major components using high-performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS). BALB/c mice were exposed to N-methyl-N-nitro-N-nitrosoguanidine (MNNG) (150 μg/mL) for 6 weeks to induce GPLs. GPL mice were administered WPL (3.75 g/kg/day and 15 g/kg/day) for an additional 8 weeks. Haematoxylin and eosin (H&E) staining was used to investigate histological alterations in gastric tissues. Expression of the T helper 1 (Th1) cell markers CD4+ and interferon-gamma (INF-γ) were tested using immunohistochemistry (IHC). Inflammatory protein and mRNA levels in the nuclear factor kappa B (NF-κB) pathway were detected using western blotting and a quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively. Results We identified and selected 110 active compounds and 146 targets from public databases and references. Four representative components of WPL were established and quantified by HPLC–MS/MS analysis. WPL attenuated MNNG-induced GPLs, including epithelial shedding, cavity fusion, basement membranes with asymmetrical thickness, intestinal metaplasia, dysplasia, pro-inflammatory Th1-cell infiltration, and INF-γ production, indicating that WPL prevents inflammation in the gastric mucosa. Furthermore, WPL reversed MNNG-induced activation of the IκB/NF-κB signalling pathway and subsequently attenuated the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase (NOX)) family members NOX2 and NOX4. Conclusion WPL attenuated GPLs by controlling the generation of pro-inflammatory elements and inhibiting the NF-κB signalling pathway in vivo.

Cell-cell communication is a vital feature involving numerous biological processes. Here, the authors develop SpaTalk, a cell-cell communication inference method using knowledge graph for spatially resolved transcriptomic data, providing valuable insights into spatial intercellular tissue dynamics.

This paper examines the influence of modification methods and the content of attapulgite (ATP) on the flame retardancy of polybutylene terephthalate (PBT). Different samples of ATP with varying modification methods and contents were blended with PBT to create composites. The composition, stability, flame retardancy, and mechanical properties of the composites were analyzed. The effect mechanism of ATP modification methods and content on the flame retardancy of PBT was analyzed. The results indicate that the addition of ATP enhanced the carbonization and flame retardancy of PBT. The addition of ATP reduced the impact strength of PBT. The inclusion of ball milled modified attapulgite (mp-ATP) resulted in an increase in the tensile strength of PBT. Furthermore, the inclusion of mp-ATP led to a mitigated decrease in the impact strength. The composites with 11%mp-ATP/PBT had the best comprehensive performance. Compared with pure PBT, the peak value of thermal release rate decreased by 70.2%, the total heat release decreased by 27.3%, and the tensile strength increased by 2.9%.

The hybrid multibend achromat (HMBA) lattice concept is adopted in some diffraction-limited storage ring designs, which can permit relatively large on-momentum dynamic aperture and relatively weak sextupoles. In a typical HMBA lattice, the main arc section is constrained by the transverse phase advances making −I transformation for sextupole cancellation. In this paper, a new HMBA lattice concept with sextupole cancellation across a straight section is proposed, where −I is made between adjacent dispersion bumps of two lattice cells. This makes the main arc section free of the phase advance constraint, and as a result, the number of bending magnets (bends) in the lattice cell and the cell tunes can be easily changed, thus providing more choices for lattice design. To achieve the large phase advances required for −I in this new concept, the split bend is used as the matching bend, which is a bend split into two pieces with a quadrupole in between. The split bend also serves to reduce the emittance, and the large phase advances also give low beta functions in the straight section enhancing the insertion device brightness. Besides, for a given emittance goal, this new HMBA lattice can have fewer bends than the typical HMBA lattice due to stronger focusing in bend unit cells, which is beneficial for saving space and suppressing intrabeam scattering effect. Two lattices are given as examples to demonstrate this new concept and show its linear and nonlinear properties and further extension is also discussed.

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR)‐based genetic screening has been demonstrated as a powerful approach for unbiased functional genomics research. Single‐cell CRISPR screening (scCRISPR) techniques, which result from the combination of single‐cell toolkits and CRISPR screening, allow dissecting regulatory networks in complex biological systems at unprecedented resolution. These methods allow cells to be perturbed en masse using a pooled CRISPR library, followed by high‐content phenotyping. This is technically accomplished by annotating cells with sgRNA‐specific barcodes or directly detectable sgRNAs. According to the integration of distinct single‐cell technologies, these methods principally fall into four categories: scCRISPR with RNA‐seq, scCRISPR with ATAC‐seq, scCRISPR with proteome probing, and imaging‐based scCRISPR. scCRISPR has deciphered genotype–phenotype relationships, genetic regulations, tumor biological issues, and neuropathological mechanisms. This review provides insight into the technical breakthrough of scCRISPR by systematically summarizing the advancements of various scCRISPR methodologies and analyzing their merits and limitations. In addition, an application‐oriented approach guide is offered to meet researchers’ individualized demands.

mRNA cancer vaccines show therapeutic potential for malignant tumors, including hepatocellular carcinoma (HCC). We optimized and synthesized stable mRNA encoding costimulator Oxford 40 ligand (OX40L). For systemic delivery, OX40L mRNAs were loaded into lipid nanoparticles (LNPs). The expression and costimulatory effects of OX40L were investigated in vitro. OX40L was expressed on the cell surface and costimulated T cells. In vivo, intratumoral injection of LNPs encapsulating OX40L mRNAs significantly reduced tumor growth and increased the survival of mice bearing H22 tumors. Importantly, CD4+ and CD8+ T cells were significantly increased in the OX40L mRNA group in vivo. Taken together, our findings provide a promising clinical strategy for immunotherapy for HCC using mRNA vaccines.

Infectious diseases have always threatened human life, but with the development of vaccines, effective strategies for preventing and controlling these diseases have become available. The global outbreak of COVID-19 ushered in the advent of mRNA vaccine technologies, which quickly led to the introduction of mRNA vaccines effective against SARS-CoV-2. The success of this approach has stimulated research into the use of mRNA vaccines in the fight against other emerging as well as remerging infectious diseases. This review examines the constructive strategies and delivery systems used in mRNA vaccines and provides an overview of current clinical trials of those vaccines in the prevention of infectious diseases. The underlying mechanisms of mRNA vaccines are also discussed, including the double-edged sword of the innate immune response. Finally, the challenges but also the potential of mRNA vaccines are considered.

Oil sludge is one of the major industrial solid wastes from petroleum production and refining. Implementing the harmless and resource treatment of oily sludge is an urgent problem to be solved. In this paper, TiO2/bentonite was prepared by sol-gel method, which was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (FT-IR), and then used in the pyrolysis process of oily sludge. The addition of TiO2/bentonite give the best quality of pyrolysis oil; maximum oil recovery was achieved when setting the pyrolysis condition at 420°C for final pyrolysis temperature, 3 h for reaction time, 10°C/min for heating rate, 100 mL/min for nitrogen flow rate and 1% for catalyst dosage. Compared with the non-catalyst, oil recovery rate can be increased from 76.06% to 84.16%, the oil content of the residue decreased from 2.23% to 1.36%. The pyrolysis recovery oil was analysed by GC-MC, and the fractions of pyrolysis oil C6-C15 were increased by 27.84%. This shows that the addition of TiO2/bentonite decreased the carbon residue, increased oil recovery and improved product quality.

Background: Surgical resection remains the primary treatment for gastrointestinal (GI) cancer, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to improve the prognosis of patients undergoing gastrointestinal tumor surgery. This meta-analysis aims to explore the efficacy of n-3 PUFAs on GI cancer patients undergoing surgery. Methods: A systematic search of PubMed, Cochrane Library databases, EMBASE (until December 2021) was conducted. PRISMA checklist was followed. The data were analyzed by RevMan v5.3.0. Results: A total of ten RCTs articles including 663 patients were studied. The analysis demonstrated that the n-3 PUFAs group significantly reduced levels of interleukin-6 (IL-6) (P = 0.001), C-reactive protein (CRP) (P

mRNA therapy is a novel anticancer strategy based on in vitro transcription (IVT), which has potential for the treatment of malignant tumors. The outbreak of the COVID-19 pandemic in the early 21st century has promoted the application of mRNA technologies in SARS-CoV-2 vaccines, and there has been a great deal of interest in the research and development of mRNA cancer vaccines. There has been progress in a number of key technologies, including mRNA production strategies, delivery systems, antitumor immune strategies, etc. These technologies have accelerated the progress and clinical applications of mRNA therapy, overcoming problems encountered in the past, such as instability, inefficient delivery, and weak immunogenicity of mRNA vaccines. This review provides a detailed overview of the production, delivery systems, immunological mechanisms, and antitumor immune response strategies for mRNA cancer vaccines. We list some mRNA cancer vaccines that are candidates for cancer treatment and discuss clinical trials in the field of tumor immunotherapy. In addition, we discuss the immunological mechanism of action by which mRNA vaccines destroy tumors as well as challenges and prospects for the future.

The phase precipitation curves of carbidic ductile iron with Nb element were simulated by the thermodynamic module in JMatPro software. The lattice mismatch between NbC and M3C was analyzed using Bramfitt two-dimensional mismatch theory, and the bonding strength (adhesive work) and interface stability (interfacial energy) of M3C(100)/NbC(110) interface were calculated by using the first principles method. The microstructure of carbidic austempered ductile iron (CADI) was observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). The results show that NbC particles precipitate previously at 1420 °C, and the lattice mismatch of M3C(100)/NbC(110) is 3.75 %. Six interface models have been constructed according to different case and termination conditions, in which interface adhesive work of Case I/C interface is the largest (1.35 J/m2), interfacial energy of Case I/Fe interface is the smallest. The covalent bond has been formed on the interface, which proves that M3C(100) and NbC(110) can form a stable interface. The experimental results confirm the precipitation of NbC particles. In addition, M3C grows beside NbC particles and they are combined tightly, indicating that NbC can act as an effective heterogeneous nucleation site of M3C.

Oncolytic virotherapy belongs to a kind of active immunotherapy, which could trigger a potent antitumor immune response, showing great potential in clinical application. OVs could induce immune responses through the dual mechanisms of selective tumor killing without destroying normal tissues and induction of systemic antitumor immunity. In this study, we successfully rescued a chimeric oncolytic influenza virus carrying a human CTLA4 antibody in the background of the A/PR/8/34 (PR8) virus. The chimeric virus, called rFlu-huCTLA4, contained the heavy and light chains of the human CTLA4 antibody in the PB1 and PA segments of the PR8 virus, respectively. The first-generation hemagglutination (HA) titers of the rFlu-huCTLA4 virus ranged from 27 to 28, which could be passaged stably in specific pathogen-free (SPF) chicken embryos from P1 to P5. The morphology and size distribution of the chimeric virus were consistent with those of the wt influenza virus. The rFlu-huCTLA4 virus could effectively replicate in various cells in time- and dose-dependent manners. ELISA assay revealed that the secreted huCTLA4 antibody levels in chicken embryos increased gradually over time. Furthermore, MTS and crystal violet analysis showed that the selective cytotoxicity of the virus was higher in hepatocellular carcinoma cells (HepG2 and Huh7) than in normal liver cells (MIHA). In vivo experiments displayed that intratumoral injection with rFlu-huCTLA4 reduced tumor growth and increased the survival of mice compared with the PR8 group. More importantly, in the rFlu-huCTLA4 group, we found that CD4+ and CD8 +T cells were significantly increased in tumor-bearing BALB/c mice. Taken together, these findings demonstrated that the chimeric oncolytic virus rFlu-huCTLA4 could selectively destroy hepatocellular carcinoma cells in vitro and in vivo and may provide a promising clinical strategy for targeted immunotherapy of HCC with the oncolytic flu virus.

Abstract Background Deciphering intra‐ and inter‐tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) and its metastasis and identifying effective therapeutic targets. However, the characteristics of different organ‐tropism metastases of GC are largely unknown. Methods Ten fresh human tissue samples from six patients, including primary tumour and adjacent non‐tumoural samples and six metastases from different organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single‐cell RNA sequencing. Validation experiments were performed using histological assays and bulk transcriptomic datasets. Results Malignant epithelial subclusters associated with invasion features, intraperitoneal metastasis propensity, epithelial–mesenchymal transition‐induced tumour stem cell phenotypes, or dormancy‐like characteristics were discovered. High expression of the first three subcluster‐associated genes displayed worse overall survival than those with low expression in a GC cohort containing 407 samples. Immune and stromal cells exhibited cellular heterogeneity and created a pro‐tumoural and immunosuppressive microenvironment. Furthermore, a 20‐gene signature of lymph node‐derived exhausted CD8+ T cells was acquired to forecast lymph node metastasis and validated in GC cohorts. Additionally, although anti‐NKG2A (KLRC1) antibody have not been used to treat GC patients even in clinical trials, we uncovered not only malignant tumour cells but one endothelial subcluster, mucosal‐associated invariant T cells, T cell‐like B cells, plasmacytoid dendritic cells, macrophages, monocytes, and neutrophils may contribute to HLA‐E‐KLRC1/KLRC2 interaction with cytotoxic/exhausted CD8+ T cells and/or natural killer (NK) cells, suggesting novel clinical therapeutic opportunities in GC. Additionally, our findings suggested that PD‐1 expression in CD8+ T cells might predict clinical responses to PD‐1 blockade therapy in GC. Conclusions This study provided insights into heterogeneous microenvironment of GC primary tumours and organ‐specific metastases and provide support for precise diagnosis and treatment.

Common bean blight (CBB), primarily caused by Xanthomonas axonopodis pv. phaseoli (Xap), is one of the most destructive diseases of common bean (Phaseolus vulgaris L.). The tepary bean genotype PI 319443 displays high resistance to Xap, and the common bean genotypes HR45 and Bilu display high resistance and susceptibility to Xap, respectively. To identify candidate genes related to Xap resistance, transcriptomic analysis was performed to compare gene expression levels with Xap inoculation at 0, 24, and 48 h post inoculation (hpi) among the three genotypes. A total of 1,146,009,876 high-quality clean reads were obtained. Differentially expressed gene (DEG) analysis showed that 1,688 DEGs responded to pathogen infection in the three genotypes. Weighted gene coexpression network analysis (WGCNA) was also performed to identify three modules highly correlated with Xap resistance, in which 334 DEGs were likely involved in Xap resistance. By combining differential expression analysis and WGCNA, 139 DEGs were identified as core resistance-responsive genes, including 18 genes encoding resistance (R) proteins, 19 genes belonging to transcription factor families, 63 genes encoding proteins with oxidoreductase activity, and 33 plant hormone signal transduction-related genes, which play important roles in the resistance to pathogen infection. The expression patterns of 20 DEGs were determined by quantitative real-time PCR (qRT-PCR) and confirmed the reliability of the RNA-seq results.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19) pandemic, represents a global crisis. Most patients developed mild/moderate symptoms, and the status of immune system varied in acute and regulatory stages. The crosstalk between immune cells and the dynamic changes of immune cell contact is rarely described. Here, we analyzed the features of immune response of paired peripheral blood mononuclear cell (PBMC) samples from the same patients during acute and regulatory stages. Consistent with previous reports, both myeloid and T cells turned less inflammatory and less activated at recovery phase. Additionally, the communication patterns of myeloid-T cell and T-B cell are obviously changed. The crosstalk analysis reveals that typical inflammatory cytokines and several chemokines are tightly correlated with the recovery of COVID-19. Intriguingly, the signal transduction of metabolic factor insulin-like growth factor 1 (IGF1) is altered at recovery phase. Furthermore, we confirmed that the serum levels of IGF1 and several inflammatory cytokines are apparently dampened after the negative conversion of SARS-CoV-2 RNA. Thus, these results reveal several potential detection and therapeutic targets that might be used for COVID-19 recovery.

Objectives: To evaluate the causes and risk factors of unplanned surgery after transcatheter closure of ventricular septal defect (VSD) in children.Methods: A total of 773 patients with VSD who had the devices transcatheter released between January 2013 and December 2018 in our institution were retrospectively reviewed. Univariate and multivariate analyses were used to identify the risk factors for unplanned surgery.Results: Twenty four patients (3.1%) underwent unplanned surgery after transcatheter closure of VSD. The most common cause for unplanned surgery was new-onset or worsening aortic regurgitation (14/24; 58.3%), followed by occluder migration (4/24; 16.7%), complete atrioventricular block (2/24; 8.3%), severe hemolysis (2/24; 8.3%), residual shunt (1/24; 4.2%), and occluder edge near the tricuspid valve chordae (1/24; 4.2%). Logistic regression analysis revealed that primary aortic valve prolapse (OR: 5.507, 95%CI: 1.673–18.123, P = 0.005); intracristal VSD (OR: 8.731, 95%CI: 2.274–33.527, P = 0.002); eccentric occluder (OR: 4.191, 95%CI: 1.233–14.246, P = 0.022); larger occluder size (OR: 1.645, 95%CI: 1.331–2.033, P < 0.001); and pulmonary artery systolic pressure ≥45 mmHg (OR: 4.003, 95%CI: 1.073–14.941, P = 0.039) were risk factors for unplanned surgery.Conclusions: New-onset or worsening aortic regurgitation was the primary cause for unplanned surgery after transcatheter closure of VSD in children. Primary aortic valve prolapse, intracristal VSD, eccentric occluder, larger occluder size, pulmonary artery systolic pressure ≥45 mmHg could increase the risk of unplanned surgery.