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BackgroundSevere acute pancreatitis (SAP) is characterized by inflammation, with inflammatory immune cells playing a pivotal role in disease progression. This study aims to understand variations in specific immune cell subtypes in SAP, uncover their mechanisms of action, and identify potential biological markers for predicting Acute Pancreatitis (AP) severity.MethodsWe collected peripheral blood from 7 untreated SAP patients and employed single-cell RNA sequencing for the first time to construct a transcriptome atlas of peripheral blood mononuclear cells (PBMCs) in SAP. Integrating SAP transcriptomic data with 6 healthy controls from the GEO database facilitated the analysis of immune cell roles in SAP. We obtained comprehensive transcriptomic datasets from AP samples in the GEO database and identified potential biomarkers associated with AP severity using the “Scissor” tool in single-cell transcriptomic data.ResultsThis study presents the inaugural construction of a peripheral blood single-cell atlas for SAP patients, identifying 20 cell subtypes. Notably, there was a significant decrease in effector T cell subsets and a noteworthy increase in monocytes compared to healthy controls. Moreover, we identified a novel monocyte subpopulation expressing high levels of PPBP and PF4 which was significantly elevated in SAP. The proportion of monocyte subpopulations with high CCL3 expression was also markedly increased compared to healthy controls, as verified by flow cytometry. Additionally, cell communication analysis revealed insights into immune and inflammation-related signaling pathways in SAP patient monocytes. Finally, our findings suggest that the subpopulation with high CCL3 expression, along with upregulated pro-inflammatory genes such as S100A12, IL1B, and CCL3, holds promise as biomarkers for predicting AP severity.ConclusionThis study reveals monocytes’ crucial role in SAP initiation and progression, characterized by distinct pro-inflammatory features intricately linked to AP severity. A monocyte subpopulation with elevated PPBP and CCL3 levels emerges as a potential biomarker and therapeutic target.

Abstract Recent studies have shown that the high incidence and low cure rate of hepatocellular carcinoma (HCC) have not improved significantly. Surgery and liver transplantation are the mainstays of prolonging the survival of HCC patients. However, the surgical resection rate of HCC patients is very low, and even after radical surgical resection, the recurrence rate at 5 years postoperatively remains high and the prognosis is very poor, so more treatment options are urgently needed. Increasing evidence suggests that cellular senescence is not only related to cancer development but may also be one of its primary driving factors. We aimed to establish a prognostic signature of senescence-associated genes to predict the prognosis and therapeutic response of HCC patients. The aim of this study was to develop a risk model associated with cellular senescence and to search for potential strategies to treat HCC. We divided HCC patients into two clusters and identified differentially expressed genes (DEGs) between clusters. In this study, low-risk patients had a better prognosis, higher levels of immune cell infiltration, and better efficacy to fluorouracil, Paclitaxel and Cytarabine chemotherapy compared to high-risk patients. To further identify potential biomarkers for HCC, we further validated the expression levels of the four signature genes in HCC and neighbouring normal tissues by in vitro experiments. In conclusion, we identified and constructed a relevant prognostic signature, which performed well in predicting the survival and treatment response of HCC patients. This helps to differentiate between low-score and high-risk HCC, and the results may contribute to precise treatment protocols in clinical practice.

Hot embossing is a manufacturing technique used to create microchannels on polymer substrates. In recent years, microchannel fabrication technology based on hot embossing has attracted considerable attention due to its convenience and low cost. A new evaluation method of microchannels, as well as an approach to obtaining optimal hot embossing conditions based on the Taguchi method, is proposed in this paper to fabricate precise microchannels for a flexible proton-exchange membrane fuel cell (PEMFC). Our self-made hot embossing system can be used to fabricate assorted types of micro-channel structures on polymer substrates according to various applications, whose bottom width, top width, height and cross-sectional area vary in the aims of different situations. In order to obtain a high effective filling ratio, a new evaluation method is presented based on the four parameters of channel structures, and the Taguchi method is utilized to arrange three main factors (temperature, force and time) affecting the hot embossing in orthogonal arrays, quickly finding the optimal condition for the embossing process. The evaluation method for microchannels proposed in this paper, compared to traditional evaluation methods, incorporates the area factor, providing a more comprehensive assessment of the fabrication completeness of the microchannels. Additionally, it allows for the quick and simple identification of optimal conditions. The experimental results indicate that after determining the optimal embossing temperature, pressure and time using the Taguchi method, the effective filling rate remains above 95%, thereby enhancing the power density. Through variance analysis, it was found that temperature is the most significant factor affecting the hot embossing of microchannels. The high filling rate makes the process suitable for PEMFCs. The results demonstrate that under optimized process conditions, a self-made hot embossing system can effectively fabricate columnar structure microchannels for PEMFCs.

Elucidating the specific interaction between graphene with various structures and asphalt is essential to promote the wide adoption of graphene modified asphalt for high-performance pavement engineering. Herein, the enhancement of modified asphalts with nano-sized graphene (NG) and micro-sized graphene (MG) were systematically investigated by using dynamic shear rheometer (DSR), atomic force microscopy (AFM) and molecular dynamics (MD) simulation at multi-scale levels. The results demonstrate that MG can significantly enhance the deformation resistance and low-temperature crack resistance of modified asphalt, compare with NG, and AFM confirm that MG can obviously affect the rearrangement of four components in asphalt to form a micellar structure with higher modulus and lower energy dissipation. MD simulation further verifies that the higher mechanical strength of large-sized graphene modified asphalt is attributed to the reduced slide movement of cavitation structures in asphalt, since the larger graphene not only has stronger π-π interaction with asphaltene and resin, but also induces one more specific interaction of hydrogen bonds (O-H···S) between these polar components. The coupling interaction facilitates the formation of more compact micelles, resulting in the improved mechanical properties of asphalt. The elucidation of graphene size effect on asphalt provides encouragement for understanding the enhancement of graphene modified asphalt.

To improve the utilization rate of cable lines while retaining sufficient security, the accurate thermal assessment of cable is significant for cable operation condition evaluation. The thermal rating for a cable joint, which is regarded as a hot spot of cable lines, is not covered by the scope of IEC 60287. While the existing publications for cable joint thermal evaluation also have some limitations. In this paper, the quasi-three-dimensional thermal model of the cable joint was established and the iterative solution method for the model is presented. Based on the model, an improved thermal rating method for the cable joint was proposed, which was implemented with monitored surface temperature and load data. The improved method was verified by the finite element method and the results showed an error of less than 5%. The superiority of the improved method was conducted by the comparison between the previously published method and the improved method. The improved method showed a better accuracy than the previously published method. The proposed method in this paper can be complementary to the IEC method, and is easy to use for the operating evaluation of cable joints in the field with the on-line condition monitoring technology.

Abstract Background Immunotherapy‐antiangiogenesis combination therapy has achieved excellent survival outcomes in hepatocellular carcinoma (HCC) in clinical trials. However, the combination therapy for HCC outside clinical trials is not well studied, and predictive factors are lacking. Here, we retrospectively analyzed the efficacy and safety of immunotherapy‐antiangiogenesis combination therapy in unresectable HCC patients in a real‐world setting. Methods We conducted a four‐center, retrospective study of unresectable HCC patients who received the combination of programmed death 1 (PD‐1) inhibitor and antiangiogenic agent between April 2018 and July 2021 in China. Results In total, 136 patients were enrolled in the cohort. The objective response rate (ORR) and disease control rate (DCR) were 38.0% and 81.8%, respectively. The median time to progression (TTP), progression‐free survival (PFS), and overall survival (OS) were 7.2, 7.3, and 19.6 months, respectively. The multivariate analysis indicated that ECOG performance status score (PS) 2 was a significantly independent negative factor of ORR. Moreover, ECOG PS 2, peritoneum metastasis and previous immunotherapy were found to be independent negative predictors of PFS. A shorter OS was associated with ECOG PS 2, peritoneum metastasis, the presence of previous immunotherapy, Child‐Pugh stage B, and high alpha‐fetoprotein (AFP) concentration. One hundred and twenty‐five patients (91.9%) reported adverse events (AEs) with any grade. Conclusion We elucidated the efficacy and safety of immunotherapy‐antiangiogenesis combination therapy and identified potential predictors for response and survival in a real‐world cohort of patients with unresectable HCC.

Styrene-butadiene-styrene (SBS)/crumb rubber (CR) blend-modified asphalt is a desirable binder for pavement engineering with both environmental and economic benefits. However, the inherent incompatibility of SBS and CR in asphalt is still a critical issue. Herein, 3D porous graphene (3DPG) with high surface area and rich micropores as reinforced additive was investigated in SBS/CR blend-modified asphalt for the first time. The experimental results demonstrate that incorporating 3DPG can effectively improve the compatibility of SBS and CR in asphalt and thus significantly enhance the high and low temperature performance and fatigue resistance of the modified asphalt, compared with that without 3DPG. Theoretical calculations further reveal that the nanopores in graphene can endow graphene with electrophilic property, providing a capability of absorbing nonpolar molecules in asphalt while the non-pore part in graphene can interact with polar molecules by conventional π − π stacking. The two forces within graphene can break the original colloidal structures of asphalt, which is conductive to the homogenous formation of SBS network and swelling of CR in asphalt, significantly promoting the pavement performance of the modified asphalt. This work presents the great potential of 3DPG as new additive to solve the inherent incompatibility of SBS/CR blend-modified asphalt for high-grade pavement engineering.

Abstract Background Sepsis is a life-threatening syndrome eliciting highly heterogeneous host responses. Current prognostic evaluation methods used in clinical practice are characterized by an inadequate effectiveness in predicting sepsis mortality. Rapid identification of patients with high mortality risk is urgently needed. The phenotyping of patients will assistant invaluably in tailoring treatments. Methods Machine learning and deep learning technology are used to characterize the patients’ phenotype and determine the sepsis severity. The database used in this study is MIMIC-III and MIMIC-IV (‘Medical information Mart for intensive care’) which is a large, public, and freely available database. The K-means clustering is used to classify the sepsis phenotype. Convolutional neural network (CNN) was used to predict the 28-day survival rate based on 35 blood test variables of the sepsis patients, whereas a double coefficient quadratic multivariate fitting function (DCQMFF) is utilized to predict the 28-day survival rate with only 11 features of sepsis patients. Results The patients were grouped into four clusters with a clear survival nomogram. The first cluster (C_1) was characterized by low white blood cell count, low neutrophil, and the highest lymphocyte proportion. C_2 obtained the lowest Sequential Organ Failure Assessment (SOFA) score and the highest survival rate. C_3 was characterized by significantly prolonged PTT, high SIC, and a higher proportion of patients using heparin than the patients in other clusters. The early mortality rate of patients in C_3 was high but with a better long-term survival rate than that in C_4. C_4 contained septic coagulation patients with the worst prognosis, characterized by slightly prolonged partial thromboplastin time (PTT), significantly prolonged prothrombin time (PT), and high septic coagulation disease score (SIC). The survival rate prediction accuracy of CNN and DCQMFF models reached 92% and 82%, respectively. The models were tested on an external dataset (MIMIC-IV) and achieved good performance. A DCQMFF-based application platform was established for fast prediction of the 28-day survival rate. Conclusion CNN and DCQMFF accurately predicted the sepsis patients’ survival, while K-means successfully identified the phenotype groups. The distinct phenotypes associated with survival, and significant features correlated with mortality were identified. The findings suggest that sepsis patients with abnormal coagulation had poor outcomes, abnormal coagulation increase mortality during sepsis. The anticoagulation effects of appropriate heparin sodium treatment may improve extensive micro thrombosis-caused organ failure.

The opening and closing of a vacuum circuit breaker in the selected phase of the system voltage and the associated electrical equipment plug in or disconnect the electrical system with minimal impact on itself and the system. To realize this and ensure the control precision and stability of its action process, this study designs the drive motor and controller of a vacuum circuit breaker actuator. Additionally, a new function-switching pseudo-differential control (FPD) strategy is based on the feedback element principle. The control strategy avoids the direct differentiation of the controlled variables and has the ability of a fast dynamic response and anti-interference. At the same time, according to the moving process of the circuit breaker contacts, the control parameters are directly assigned to the system in stages, which reduces the amount of calculation and enhances the response speed of the control system. According to the research on the motor actuator movement process, the motor actuator and its control system of a 40.5 kV vacuum circuit breaker are developed and verified by closing operation in the selected phase, and the experimental results show the effectiveness of the proposed control strategy.

Abstract Osteosarcoma is an aggressive malignant bone sarcoma worldwide. A causal gene network with specific functions underlying both the development and progression of OS was still unclear. Here we firstly identified the differentially expressed genes (DEGs) between control and OS samples, and then defined the hub genes and top clusters in the protein–protein interaction (PPI) network of these DEGs. By focusing on the hub gene TYROBP in the top 1 cluster, a conserved TYROBP co-expression network was identified. Then the effect of the network on OS overall survival was analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Set Enrichment Analysis (GSEA) were used to explore the functions of the network. XCell platform and ssGSEA algorithm were conducted to estimate the status of immune infiltration. ChEA3 platform, GSEA enrichment analysis, and Drug Pair Seeker (DPS) were used to predict the key transcription factor and its upstream signal. We identified the downregulated SPI1-TYROBP-FCER1G network in OS, which were significantly enriched in immune-related functions. We also defined a two-gene signature (SPI1/FCER1G) that can predict poorer OS overall survival and the attenuated immune infiltration when downregulated. The SPI1-TYROBP-FCER1G network were potentially initiated by transcription factor SPI1 and would lead to the upregulated CD86, MHC-II, CCL4/CXCL10/CX3CL1 and hence increased immune infiltrations. With this study, we could better explore the mechanism of OS oncogenesis and metastasis for developing new therapies.

BackgroundIn the past decade, considerable research efforts on gastric cancer (GC) have been expended, however, little advancement has been made owing to the lack of effective biomarkers and treatment options. Herein, we aimed to examine the levels of expression, mutations, and clinical relevance of HMGs in GC to provide sufficient scientific evidence for clinical decision-making and risk management.MethodsGC samples were obtained from The Cancer Genome Atlas (TCGA). University of California Santa Cruz (UCSC) XENA, Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, LinkedOmics, and DAVID databases were employed. The “ggplot2” package in the R software (×64 3.6.3) was used to thoroughly analyze the effects of HMGs. qRT-PCR was performed to assess HMG levels in GC cell lines.ResultsA total of 375 GC tissues and 32 paraneoplastic tissues were analyzed. The levels of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN1, HMGN2, and HMGN4 expression were increased in GC tissues relative to normal gastric tissues. HMGA1, HMGA2, HMGB1, HMGB2, and HMGB3 were highly expressed in GC cell lines. The OS was significantly different in the group showing low expressions of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN2, HMGN3, and HMGN5. There was a significant difference in RFS between the groups with low HMGA2, HMGB3, and high HMGN2 expression. The levels of HMGA2, HMGB3, and HMGN1 had a higher accuracy for prediction to distinguish GC from normal tissues (AUC value > 0.9). HMGs were tightly associated with immune infiltration and tumor immune escape and antitumor immunity most likely participates in HMG-mediated oncogenesis in GC. GO and KEGG enrichment analyses showed that HMGs played a vital role in the cell cycle pathway.ConclusionsOur results strongly suggest a vital role of HMGs in GC. HMGA2 and HMGB3 could be potential markers for prognostic prediction and treatment targets for GC by interrupting the cell cycle pathway. Our findings might provide renewed perspectives for the selection of prognostic biomarkers among HMGs in GC and may contribute to the determination of the optimal strategy for the treatment of these patients.

Abstract Vertical graphene (VG), possessing superior chemical, physical, and structural peculiarities, holds great promise as a building block for constructing a high‐energy density lithium‐sulfur (Li‐S) battery. Therefore, it is desirable to develop a new VG growth technique with a novel structure to enable wide applications. Herein, we devise a novel complex permittivity‐dependent plasma confinement‐assisted VG growth technique, via asymmetric growing a VG layer on one side of N‐doped carbon nanofibers for the first time, using a unique lab‐built high flux plasma‐enhanced chemical vapor deposition system, as a bifunctional nanofiber membrane to construct Li‐S batteries with low negative/positive (N/P) and electrolyte/sulfur (E/S) ratios. The unique nanofiber membrane could simultaneously protect the cathode and anode, enabling an excellent electrochemical performance with low N/P and E/S ratios in Li‐S batteries. Such a full cell delivers high gravimetric energy density and volumetric energy density of 340 Wh kg−1 and 547 Wh L−1, respectively, at low N/P (2:1) and E/S (4:1) ratios. Furthermore, a pouch cell achieves a high areal capacity of 7.1 mAh cm−2 at a sulfur loading of 6 mg cm−2. This work put forward a novel pathway for the design of high‐energy density Li‐S batteries.

Microgrid operation planning is crucial for ensuring the safe and efficient output of distributed energy resources (DERs) and stable operation of the microgrid power system. The integration of hydrogen fuel cells into microgrids can increase the absorption rate of renewable energy, while the incorporation of lithium batteries facilitates the adjustment of microgrid power supply voltage and frequency, ensuring the three-phase symmetry of the system. This paper proposes an economic scheduling method for a grid-connected microgrid that considers demand response and combines hydrogen and electricity. Based on the operating costs of renewable energy, maintenance and operation costs of nonrenewable energy, interaction costs between the microgrid and main grid, and pollution control costs, an optimization model for dispatching a hydrogen–electric hybrid microgrid under grid-connected mode is established. The primary objective is to minimize the operating cost, while the secondary objective is to minimize the impact on the user’s power consumption comfort. Therefore, an improved demand response strategy is introduced, and an enhanced sparrow search algorithm (ISSA) is proposed, which incorporates a nonlinear weighting factor and improves the global search capability based on the sparrow search algorithm (SSA). The ISSA is used to solve the optimal operation problem of the demand-response-integrated microgrid. After comparison with different algorithms, such as particle swarm optimization (PSO), whale optimization algorithm (WOA), sooty tern optimization algorithm (STOA), and dingo optimization algorithm (DOA), the results show that the proposed method using demand response and ISSA achieves the lowest comprehensive operating cost for the microgrid, making the microgrid’s operation safer and with minimum impact on user satisfaction. Therefore, the feasibility of the demand response strategy is demonstrated, and ISSA is proved to have better performance in solving optimal operation planning problems for hydrogen–electric hybrid microgrids.

Abstract Rechargeable zinc–air batteries (ZABs) have attracted great interests for emerging energy applications. Nevertheless, one of the major bottlenecks lies in the fabrication of bifunctional catalysts with high electrochemical activity, high stability, low cost, and free of precious and rare metals. Herein, a high‐performance metal‐free bifunctional catalyst is synthesized in a single step by regulating radicals within the recently invented high‐flux plasma enhanced chemical vapor deposition (HPECVD) system equipped with in situ plasma diagnostics. Thus‐derived (N, O)‐doped vertical few‐layer graphene film (VGNO) is of high areal population with perfect vertical orientation, tunable catalytic states, and configurations, thus enabling significantly enhanced electrochemical kinetic processes of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with reference to milestone achievements to date. Application of such VGNO to aqueous ZABs (A‐ZABs) and flexible solid‐state ZABs (S‐ZABs) exhibited high discharge power density and excellent cycling stability, which remarkably outperformed ZABs using benchmarked precious‐metal based catalysts. The current work provides a solid basis toward developing low‐cost, resource‐sustainable, and eco‐friendly ZABs without using any metals for outstanding OER and ORR catalysis.

The crucial role of CD4+ and CD8+ T cells in shaping and controlling immune responses during immune disease and cancer development has been well established and used to achieve marked clinical benefits. CD3+CD4-CD8- double-negative (DN) T cells, although constituting a rare subset of peripheral T cells, are gaining interest for their roles in inflammation, immune disease and cancer. Herein, we comprehensively review the origin, distribution and functions of this unique T cell subgroup. First, we focused on characterizing multifunctional DN T cells in various immune responses. DN regulatory T cells have the capacity to prevent graft-versus-host disease and have therapeutic value for autoimmune disease. T helper-like DN T cells protect against or promote inflammation and virus infection depending on the specific settings and promote certain autoimmune disease. Notably, we clarified the role of DN tumor-infiltrating lymphocytes and outlined the potential for malignant proliferation of DN T cells. Finally, we reviewed the recent advances in the applications of DN T cell-based therapy for cancer. In conclusion, a better understanding of the heterogeneity and functions of DN T cells may help to develop DN T cells as a potential therapeutic tool for inflammation, immune disorders and cancer.

Abstract Vertically aligned carbon nanotubes (VACNTs) present an exciting avenue for nanoelectronics due to their predetermined orientation and exceptional transport capabilities along the tube length, with the potential to be employed in a variety of optoelectronic applications. However, growth of VACNTs using conventional chemical vapor deposition (CVD) methods requires elevated temperatures (>720 °C) and therefore, the suitability of commonly used transparent conductive oxide (TCO) glasses, such as fluorine‐doped tin oxide (FTO) and indium‐tin oxide (ITO), as the substrates for nanotube growth are limited by their temperature‐sensitive nature. Here, the successful growth of multi‐walled VACNTs directly onto commonly used TCO glasses, FTO and ITO, using the photo‐thermal chemical vapor deposition (PTCVD) growth method is reported. The benefit of reflection, within the infrared region, of the TCO substrate and the effect of surface roughness on the growth of VACNTs is investigated. The application of VACNTs on ITO in inverted planar perovskite solar cells is investigated, which shows superior charge transfer, larger grain sizes in the perovskite film, and a champion device efficiency approaching 16%.

Using the data of 40 host countries during 2010 to 2017, we investigate whether the Belt and Road Initiative (BRI) has brought new opportunities to countries along the routes to participate in global value chains (GVCs). We employ a difference-in-differences (DID) method with propensity score matching (PSM) to solve the self-selection bias problem. The results indicate that BRI has a significant positive effect on promoting the countries along the routes to participate in GVCs, and the effect is lagging and fluctuant. Specifically, we find that the promotion effects are particularly significant in the second year of the BRI’s implementation. The heterogeneity analysis of Belt and Road (BR) countries shows that there remains a significant positive effect on developing BR countries as before, while the opposite is true for developed BR countries.

Background & Aims Endothelial precursor cell (EPC) dysfunction is one of the risk factors for diabetes mellitus (DM) which results in delayed wound healing. Rosiglitazone (RSG) is a frequently prescribed oral glucose-lowering drug. Previous studies have shown the positive effects of RSG on ameliorating EPC dysfunction in diabetic patients. Interestingly, knowledge about RSG with regard to the wound healing process caused by DM is scarce. Therefore, in this study, we investigated the possible actions of RSG on wound healing and the related mechanisms involved in db/db diabetic mice. Methods Db/db mice with spontaneous glucose metabolic disorder were used as a type 2 DM model. RSG (20 mg/kg/d, i.g.,) was administered for 4 weeks before wound creation and bone marrow derived EPC (BM-EPC) isolation. Wound closure was assessed by wound area and CD31 staining. Tubule formation and migration assays were used to judge the function of the BM-EPCs. The level of vascular endothelial growth factor (VEGF), stromal cell derived factor-1α (SDF-1α) and insulin signaling was determined by ELISA. Cell viability of the BM-EPCs was measured by CCK-8 assay. Results RSG significantly accelerated wound healing and improved angiogenesis in db/db mice. Bioactivities of tube formation and migration were decreased in db/db mice but were elevated by RSG. Level of both VEGF and SDF-1α was increased by RSG in the BM-EPCs of db/db mice. Insulin signaling was elevated by RSG reflected in the phosphorylated-to-total AKT in the BM-EPCs. In vitro, RSG improved impaired cell viability and tube formation of BM-EPCs induced by high glucose, but this was prevented by the VEGF inhibitor avastin. Conclusion Our data demonstrates that RSG has benefits for wound healing and angiogenesis in diabetic mice, and was partially associated with improvement of EPC function through activation of VEGF and stimulation of SDF-1α in db/db mice.

A projective synchronization scheme for a kind of n-dimensional discrete dynamical system is proposed by means of a linear feedback control technique. The scheme consists of master and slave discrete dynamical systems coupled by linear state error variables. A kind of novel 3-D chaotic discrete system is constructed, to which the test for chaos is applied. By using the stability principles of an upper or lower triangular matrix, two controllers for achieving projective synchronization are designed and illustrated with the novel systems. Lastly some numerical simulations are employed to validate the effectiveness of the proposed projective synchronization scheme.