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result(s) for
"Liang, Kaijie"
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Bridging mechanism and clinic: unlocking the full potential of oncolytic virus-based immunotherapy
by
Tang, Hengyi
,
Liang, Kaijie
,
Zhang, Xiaotian
in
Animals
,
Biomedical and Life Sciences
,
Biomedicine
2026
Oncolytic viruses (OVs) have emerged as a distinctive class of cancer therapeutics capable of coupling direct tumor cell lysis with broad immune activation, thereby reshaping antitumor immunity beyond the capacities of conventional modalities. Despite substantial progress, the clinical translation of OVs remains constrained by challenges such as inefficient delivery, restricted tumor selectivity, premature immune clearance and safety concerns, all of which collectively limit therapeutic efficacy. Recent advances in genetic engineering, viral retargeting and high-dimensional profiling technologies have begun to clarify the molecular and microenvironmental determinants of OV tropism and activity, providing new opportunities to optimize OV design.
In this review, we synthesize current OV classifications, mechanisms of action and clinical developments, and highlight emerging innovations spanning synthetic engineering, targeted delivery platforms and combination therapy strategies—including those integrating OVs with immunotherapies, targeted agents and conventional modalities—to amplify therapeutic potency and overcome resistance. Together, these perspectives provide an integrated framework for understanding OV biology, underscore the need to address persistent barriers to safe and effective clinical deployment, and outline key priorities for advancing OVs toward their potential as a foundational component of next-generation, personalized cancer immunotherapy.
Journal Article
Research on Temperature-Rise Characteristics of Motor Based on Simplified Lumped-Parameter Thermal Network Model
2024
The thermal management of a driving motor is related to the performance and economy of the vehicle. The lumped-parameter thermal network (LPTN) method can provide a model basis for motor temperature-rise control and effectively shorten the development cycle of motor thermal performance design. In this study, an 80 kw water-cooled permanent magnet synchronous motor was used and the accurate thermal model of a motor was built using the LPTN. On the basis of the accurate thermal model, the simplified thermal model of a motor was obtained by reducing the complexity of the model. The temperature-rise test of the end winding and magnetic steel of the motor was carried out under some working conditions. The test conditions were selected according to continuous external characteristics and operating characteristics of the motor. Compared with the experimental results, the temperature-rise error of the two thermal models was less than 5%. The temperature-rise error of the simplified thermal model was less than 3% compared with the accurate thermal model. Therefore, the simplified thermal model can be used to quickly predict the temperature rise of the motor.
Journal Article
Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer
by
Zhang, Xin
,
Yang, Xueyi
,
Liu, Baorui
in
Antigen (tumor-associated)
,
Antigens
,
Antitumor activity
2023
Despite the successful application of chimeric antigen receptor (CAR)‐T cell therapy in hematological malignancies, the treatment efficacy in solid tumors remains unsatisfactory, largely due to the highly immunosuppressive tumor microenvironment and low density of specific tumor antigens. Natural killer group 2 member D (NKG2D) CAR‐T cells have shown promising treatment effects on several cancers such as lymphoma and multiple myeloma. However, the application and efficacy of NKG2D‐CAR‐T cells in gastric cancer (GC) still needs further exploration. This study identified a novel combination immunotherapy strategy with Dickkopf‐1 (DKK1) inhibition and NKG2D‐CAR‐T cells, exerting synergistic and superior antitumor effect in GC. We show that the baseline expression of NKG2D ligands (NKG2DLs) is at low levels in GC tissues from The Cancer Genome Atlas and multiple GC cell lines including NCI‐N87, MGC803, HGC27, MKN45, SGC7901, NUGC4, and AGS. In addition, DKK1 inhibition by WAY‐262611 reverses the suppressive tumor immune microenvironment (TIME) and upregulates NKG2DL expression levels in both GC cell lines and GC tissues from a xenograft NCG mouse model. DKK1 inhibition in GC cells markedly improves the immune‐activating and tumor‐killing ability of NKG2D‐CAR‐T cells as shown by cytotoxicity assays in vitro. Moreover, the combination therapy of NKG2D‐CAR‐T and WAY‐262611 triggers superior antitumor effects in vivo in a xenograft NCG mouse model. In sum, our study reveals the role of DKK1 in remodeling GC TIME and regulating the expression levels of NKG2DLs in GC. We also provide a promising treatment strategy of combining DKK1 inhibition with NKG2D‐CAR‐T cell therapy, which could bring new breakthroughs for GC immunotherapy. Our study reveals the role of Dickkopf‐1 (DKK1) in remodeling gastric cancer (GC) tumor immune microenvironment and regulating the expression levels of natural killer group 2 member D (NKG2D) ligands in GC. We also provide a promising treatment strategy of combining DKK1 inhibition with NKG2D‐ chimeric antigen receptor‐T cell therapy, which could bring new breakthroughs for GC immunotherapy.
Journal Article
971 Immature neutrophils inhibit anti-tumor immunity and impede checkpoint blockade therapy in bone metastases
2023
BackgroundDespite the important breakthroughs of immune checkpoint blockade (ICB) therapy in multiple primary cancers, responses of ICB therapy in bone metastases remain extremely poor, largely due to the highly immunosuppressive bone metastasis microenvironment. Tumor-associated neutrophils have recently been reported to have critical impact in the responses of cancer immunotherapies. However, the role of neutrophils within bone metastasis microenvironment is still unknown. Here, we aim to explore the impact of immature neutrophils druing bone metastasis progression, and assess immunotherapies targeting neutrophils to improve ICB therapy in bone metastases.MethodsRNA-seq and mass-spectrum data of bone metastasis samples from publicly available databases and our center were obtained. Mouse bone metastasis models from gastric, breast and lung cancer were established, and in vivo treatment efficacy of DKK1 and/or PD-1 blockade was evaluated by micro-computed tomography (CT), micro-magnetic resonance imaging (MRI) and immunohistochemistry (IHC) staining. Impacts of DKK1 on the bone-tumor microenvironment were explored via in vivo immune analysis. The impact of DKK1 on the maturation, function and phenotype of neutrophils was analyzed via in vitro co-culture models.ResultsThe proportion of neutrophils within bone metastasis microenvironment of breast cancer model was gradually increased, and neutrophils gradually became immature (Ly6Ghigh, CD101-, CXCR2-, CXCR4+) during bone metastasis progression, with immature neutrophils occupied the most proportion (80%) at day 14. Meanwhile, analysis of bone metastasis samples from patients identified that DKK1 expression was significantly up-regulated in both mRNA and protein levels. DKK1 directly induced neutrophils to become immature in vitro, and immature neutrophils induced by DKK1 exhibited strong immunosuppressive capacity to inhibit the tumor-killing ability of CD8+ T cells in vitro co-culture models. Next, using multiple bone metastasis mouse models, we observed that DKK1 blockade with murine DKK1 antibody (mDKN-01) significantly controlled the tumor burden of bone metastases and alleviated bone destruction. Results of flow cytometry and immunofluorescence staining on bone metastasis samples demonstrated immature neutrophils were effectively reversed, and both innate and adaptive anti-tumor immunity were improved after DKK1 blockade. Finally, reversion of immature neutrophils by DKK1 blockade remarkedly enhanced the efficacy of PD-1 blockade in bone metastases, and complete response (CR) was observed with combined blockade of DKK1 and PD-1.ConclusionsOur study provides novel insights into the critical impact of the immature neutrophils in the immunosuppressive bone metastasis microenvironment. DKK1 is a potential immunotherapeutic target for bone metastases, and dual blockade of DKK1 and PD-1 is a promising combination immunotherapy strategy for patients with bone metastasis.Ethics ApprovalCollection and analysis of tumor samples were approved by the Ethics Committee of Nanjing University Medical School Affiliated Drum Tower Hospital (2021–324-01). All animal experiments were approved by the Institutional Animal Care and Use Committee of Drum Tower Hospital (2020AE01064).ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Journal Article
940 Targeting DKK1 to reverse immunosuppressive macrophages and enhance PD-1 blockade therapy in gastric cancer
2021
BackgroundGastric cancer (GC) is a highly heterogeneous and immunosuppressive cancer type with poor prognosis. Current immunotherapies like immune checkpoint blockade (ICB) have very modest therapeutic effect in GC patients, reflecting urgent need for exploring new immunotherapeutic targets.MethodsIHC and mRNA analysis of 384 patients from Drum Tower Hospital Cohort and 1192 patients from other databases were performed to investigate Dickkopf-1 (DKK1) expression and local immune status. The MFC-challenged subcutaneous and abdominal dissemination GC models were established, and the impact of DKK1 blockade on gastric tumor immune microenvironment (TIME) and anti-tumor responses was explored by flow cytometry and RNA sequencing. In vivo immune cell-depletion GC models were constructed to further assess the function of DKK1 on different immune cell types. RAW264.7 and mouse bone marrow derived macrophages (BMDMs) were employed to analyze DKK1 modulation on macrophages in vitro by Cytometric Bead Array, flow cytometry and western bolt.ResultsIn present study, we found high DKK1 expression is associated with poor overall survival and worse immune status in GC patients. DKK1 blockade could improve gastric TIME, including increased accumulation and activation of CD8+ T cells and NK cells, and trigger an effective anti-tumor response both in subcutaneous and abdominal dissemination GC models. DKK1 directly induces macrophages towards an immunosuppressive phenotype, while the TIME improvement and tumor reduction depend on the reversion of immunosuppressive macrophages mediated by DKK1 blockade. Furthermore, combined inhibition of PD-1 and DKK1 could achieve superior anti-tumor effect on GC models.ConclusionsThus, our work identifies a new role of DKK1 to induce immunosuppressive TIME through macrophage modulation, and reveals DKK1 to be a novel and promising immunotherapeutic target for GC.Ethics ApprovalThe collection and analysis of tumor tissue sections were approved by the Ethics Committee of Nanjing University Medical School Affiliated Drum Tower Hospital (2021-324-01). All animal experiments were approved by the Institutional Animal Care and Use Committee of Drum Tower Hospital (approval number: 2020AE01064).
Journal Article
The effect of porous media on the thermal storage performance of salinity-gradient solar pond
2023
A solar pond is a system that uses a salt concentration gradient to store heat. The application of the system is conducive to solving the problems of long production cycles, low brine temperature, and salt algae in the solar pond lithium extraction process and the solar pond potassium enrichment process. Based on this, our research group laid porous media at the bottom of the solar pond and utilized the heat storage and adsorption capacity of porous media to improve the thermal storage performance of the solar pond. The experimental results show that foam ceramics have good thermal storage performance and the ability to reduce turbidity. Laying foam ceramics on the bottom of the solar pond can not only increase the thermal storage performance of LCZ but also help reduce the turbidity of the pool water. After adding porous media, the heat extraction position of the solar pool moves from the junction of LCZ and NCZ to the bottom of LCZ. In addition, adding transparent film on the upper surface of the solar pond is also conducive to improving the thermal storage performance of the solar pond and reducing the turbidity of the solar pond.
Journal Article
Improvement of Engine Combustion and Emission Characteristics by Fuel Property Modulation
by
Jiang, Zhipeng
,
Shao, Zhengri
,
Liang, Kaijie
in
Air pollution
,
Air quality management
,
Analysis
2024
The sustainability of diesel engines has come to the forefront of research with the growing global interest in reducing greenhouse gas emissions and improving energy efficiency. The aim of this paper is to support the goal of sustainable development by improving the volatile properties of diesel fuel to promote cleaner combustion in engines. In order to study the effect of diesel fuel volatility on spraying, combustion, and emission, the tests were carried out with the help of the constant volume chamber (CVC) test rig and an engine test rig, respectively. CVC test: A high-speed video camera recorded the spray characteristics of different volatile fuels in a constant-volume combustion bomb. The effects of different rail pressures and ambient back pressures on the spray characteristics were investigated. Engine test: The combustion and emission characteristics of different volatile diesel fuels under different load conditions (25%, 50%, 75%) were investigated in a four-stroke direct-injection diesel engine with the engine speed fixed at 2000 rpm. The test results show that as the rail pressure increases and the ambient pressure decreases, the spray characteristics of the fuels tend to increase; for the more volatile fuels, although reducing the spray tip penetration, the spray projected area and spray cone angle increase, which is conducive to improving the homogeneity of the fuel and air mixing in the cylinder. The improvement of fuel volatility can form more and better-quality mixtures within the ignition delay time (ID), resulting in a 1–2% increase in peak cylinder pressure and a 2–4% increase in peak heat release. For different loads, pre-injection heat release is generated to redefine the ID and combustion duration (CD). Improved fuel volatility effectively reduces carbon monoxide (CO) emissions by about 8–10% and hydrocarbon (HC) emissions by about 13–16%, but it increases nitrogen oxide (NOx) emissions by about 8–11%. Analyzing from the perspective of particulate matter (PM), combined with the aromatic content of volatile fuels, it is recommended to use fuels with moderate volatility and aromatic content under low load conditions, and at medium to large loads, the volatility of the fuel has less weight on particulates and more weight on aromatics, so it is desirable to use the fuel with the lowest volatility and lowest aromatic content of the fuel selected.
Journal Article
Thermodynamic, Economic, and Environmental Analyses and Multi-Objective Optimization of Dual-Pressure Organic Rankine Cycle System with Dual-Stage Ejector
2024
A novel dual-pressure organic Rankine cycle system (DPORC) with a dual-stage ejector (DE-DPORC) is proposed. The system incorporates a dual-stage ejector that utilizes a small amount of extraction steam from the high-pressure expander to pressurize a large quantity of exhaust gas to perform work for the low-pressure expander. This innovative approach addresses condensing pressure limitations, reduces power consumption during pressurization, minimizes heat loss, and enhances the utilization efficiency of waste heat steam. A thermodynamic model is developed with net output work, thermal efficiency, and exergy efficiency (Wnet, ηt, ηex) as evaluation criteria, an economic model is established with levelized energy cost (LEC) as evaluation index, an environmental model is created with annual equivalent carbon dioxide emission reduction (AER) as evaluation parameter. A comprehensive analysis is conducted on the impact of heat source temperature (TS,in), evaporation temperature(T2), entrainment ratio (Er1, Er2), and working fluid pressure (P5, P6) on system performance. It compares the comprehensive performance of the DE-DPORC system with that of the DPORC system at TS,in of 433.15 K and T2 of 378.15 K. Furthermore, multi-objective optimization using the dragonfly algorithm is performed to determine optimal working conditions for the DE-DPORC system through the TOPSIS method. The findings indicate that the DE-DPORC system exhibits a 5.34% increase in Wnet and ηex, a 58.06% increase in ηt, a 5.61% increase in AER, and a reduction of 47.67% and 13.51% in the heat dissipation of the condenser and LEC, compared to the DPORC system, highlighting the advantages of this enhanced system. The optimal operating conditions are TS,in = 426.74 K, T2 = 389.37 K, Er1 = 1.33, Er2 = 3.17, P5 = 0.39 MPa, P6 = 1.32 MPa, which offer valuable technical support for engineering applications; however, they are approaching the peak thermodynamic and environmental performance while falling short of the highest economic performance.
Journal Article
PDRNet: A Novel Physical Feature-Driven Residual Network for Motor Vibration Signal Denoising
2025
Bearing signal denoising is a pivotal task in predictive maintenance and condition monitoring of industrial machinery. However, conventional denoising methods often face difficulties in simultaneously suppressing noise and preserving essential physical features. To address this challenge, we propose a novel denoising framework that incorporates physical feature priors derived from low-dimensional manifold-based simulated data. Specifically, a regression branch—constructed using convolutional and residual neural networks—is integrated into the main denoising model to exploit the intrinsic structure of bearing signals. By embedding manifold-informed priors, the regression branch enhances denoising performance and ensures the retention of critical physical features. Experimental results demonstrate that the proposed approach surpasses traditional methods in both signal denoising and bearing fault diagnosis. Notably, the incorporation of manifold-derived priors improves the model’s capability to capture the underlying physical characteristics of the signals, indicating that the network has learned their inherent features rather than simply minimizing the loss function. Overall, this study introduces a robust denoising paradigm for complex industrial environments where bearing signals exhibit significant variability.
Journal Article
Uncover the genetic basis of processing quality related traits in common wheat (Triticum aestivum L.) using genome-wide association mapping
2026
Improving wheat processing quality is one of the primary objectives in modern wheat breeding. Among various wheat quality parameters, SDS sedimentation volume (SSV), test weight (TW), and water absorption rate (WAR), significantly influence end-use flour quality. The Huang-Huai Winter Wheat Region (HHWWR) is the largest commercial wheat production region in China, making the breeding of high-quality wheat varieties adapted to this region particularly important.
In this study, genome-wide association study (GWAS) analysis for grain quality traits were conducted based on 310 wheat varieties collected from HHWWR. The SSV, TW, and WAR were evaluated at Anyang of Henan and Yangling of Shaanxi at the 2022-2023 and 2023-2024 cropping seasons.
Totally, three stable SSV related loci were detected on chromosomes 1A and 4A, explaining 7.2-9.2% of the phenotypic variation (PVE). Seven stable TW loci were distributed on chromosomes 1A, 1B, 4A, 5A, 6D, and 7B, with PVE ranging from 7.0% to 20.1%. In addition, 5 stable WAR-related loci were found on chromosomes 1A, 3B, 4B, and 4D, and accounting for 7.0-8.7% of PVE. Among these, 5 loci co-localized with known genes or loci, whereas the remaining 10 loci are potentially novel. We further identified several candidate genes involved in various biological pathways in plants, including growth and development, stress responses, metabolic regulation, and signal transduction. Moreover, five Kompetitive Allele-Specific PCR (KASP) markers,
,
,
,
, and
, were developed and validated in 123 common wheat accessions. This study provides stable loci and validated KASP markers, thereby paving the way for the molecular improvement of wheat quality through marker-assisted breeding.
Journal Article