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Summary: The delivery of bispecific antibodies (BsAbs) targeting B‐cell maturation antigen (BCMA) and CD3 using the gene therapy approach is a promising alternative for BsAb administration in patients with multiple myeloma (MM). In the present study, we evaluated the efficacy of this approach using a xenograft model. Tumour growth was significantly delayed in mice treated with single electroporation‐enhanced intramuscular injection of plasmid DNA encoding BCMA/CD3 BsAb in contrast to the vehicle control‐treated group. Limited toxicity was observed following treatment. This study demonstrates that the gene therapy‐based approach for the delivery of BCMA/CD3 BsAb is effective and safe for the treatment of MM. [ABSTRACT FROM AUTHOR]

Wind power generation is the major approach to wind energy utilization. However, due to the volatility, intermittent, and controllability of wind power, it is difficult to control and scheduling of wind power, which brings challenges to the grid-connected operation and dispatch of wind power. Therefore, accurate power prediction of the wind power generation system is worthy of in-depth study. And this paper proposes a wind power prediction model based on logistic chaos atom search optimization (LCASO) optimized back-propagation (BP) neural network, aiming to achieve accurate and efficient power prediction. Moreover, this work utilizes data preprocessing to obtain more precise prediction results and related prediction evaluation indexes to quantificationally compare the effect of the proposed one with other prediction models based on GA-BP neural network and PSO-BP neural network. In contrast with the BP neural network, GA-BP neural network, and PSO-BP neural network, the simulation tests verify the comprehensive prediction performance and wider applicability of LCASO-BP neural network-based power prediction model. [ABSTRACT FROM AUTHOR]

Background: Diffuse myocardial interstitial fibrosis (DMIF) is a key factor for heart failure (HF) in diabetic cardiomyopathy. MRI T1‐mapping technique can quantitatively evaluate DMIF. Purpose: To evaluate of early DMIF in a type 1 diabetes mellitus (T1DM) mouse model through 7.0 T MRI T1 mapping. Study Type: Prospective. Animal Model: A total of 50 8‐week‐old C57Bl/6J male mice were divided into control (n = 20) and T1DM (n = 30) groups. Field Strength/Sequence: A 7.0 T small animal MRI; gradient echo Look–Locker inversion recovery T1‐mapping sequence; cine MRI. Scans were acquired in control and T1DM mice every 4 weeks until 24 weeks. Assessment: End‐diastolic volume (EDV), end‐systolic volume (ESV), ejection fraction (EF), left ventricle (LV) mass, fractional shortening (FS), and E/A ratio. They were evaluated through echocardiography and cine MRI. The extracellular volume fraction (ECV) was calculated. Sirius Red staining was performed and calculated collagen volume fraction (CVF). Statistical Tests: Differences in ECV and CVF between two groups were analyzed using one‐way analysis of variance. The correlation between ECV and CVF was assessed using Pearson's correlations. Results: Compared with the control group, a progressive decrease in FS, EF, and E/A ratio was observed in the T1DM group. Both ECV and CVF values gradually increased during diabetes progression. A significant increase in ECV and CVF values was observed at 12 weeks (ECV: 32.5% ± 1.6% vs. 28.1% ± 1.8%; CVF: 6.9% ± 1.8% vs. 3.3% ± 1.1%). ECV showed a strong correlation with CVF (r = 0.856). Data Conclusion: ECV is an accurate and feasible imaging marker that can be used to quantitatively assess DMIF changes over time in T1DM mice. ECV has potential to accurately detect DMIF in the early stage and may be a useful imaging tool to assess the need for early intervention in T1DM mice. Evidence Level: 1 Technical Efficacy: Stage 3. [ABSTRACT FROM AUTHOR]

Mast cells (MCs), central players in allergy and parasitic infections, play key roles in inflammation and fibrosis. Here, the impact of MCs on the progression of Coxsackievirus B3 (CVB3)‐induced viral myocarditis (VMC) and fibrosis was investigated using MC‐deficient KitW‐sh mice. Viral titres, cellular infiltrates and heart pathologies were evaluated and compared with wild‐type (WT) mice during acute CVB3 infection of C57BL/6 mice. CVB3 infection induced an increased accumulation and degranulation of MCs in the hearts of mice during acute infection. MC‐deficient KitW‐sh mice had slightly higher viral titres, decreased VMC and cardiac fibrosis and improved cardiac dysfunction compared to WT mice via decreasing cardiac influx of Ly6Chigh monocytes/macrophages (Mo/Mφ). While bone marrow‐derived MC reconstitution decreased viral titre and worsened improved survival and VMC severity in Wsh mice. MC‐fibroblasts co‐culture revealed a cardiac MC‐fibroblasts crosstalk during early infection: fibroblasts trigger MC degranulation and secretion of CCL2 and tumour necrosis factor alpha (TNF‐α) via producing early stem cell factor (SCF); while MCs‐fibrogenic mediators (TNF‐α) stimulate fibroblasts to increase CCL2, α‐smooth muscle actin (SMA), collagen and transforming growth factor beta（TGFβ) expression, thus aggravating cardiac fibrosis. MCs and fibroblast‐derived CCL2s are both essential for cardiac Ly6Chigh Mo/Mφ influx. Administration of recombinant mouse SCF to CVB3‐infected mice aggravates VMC via accelerating MCs accumulation and cardiac influx of Ly6Chi Mo/Mφ. Collectively, our data highlight an early MC‐fibroblast crosstalk and SCF/MC/CCL2/Mo/Mφ axis as important mechanisms required for triggering VMC and myocardial fibrosis. This finding indicates critical roles of MCs in initiating and modulating cardiac innate response to CVB3 and has an implication in developing new and more effective treatments for VMC. [ABSTRACT FROM AUTHOR]

Background: Myelodysplastic syndrome (MDS) is a clonal disease of hematopoietic cells, characterized by hematopoietic cell hematopoiesis and a high risk of transformation into acute myeloid leukemia (AML). Although the underlying mechanism is unclear, MDS is often associated with immune system disorders, especially cellular immune abnormalities. We analyzed the number of lymphocyte subsets by flow cytometry assay and explored the alteration of lymphocyte subsets in MDS. Methods: Healthy controls, inpatients with primary MDS and patients with AML diagnosed from January 2017 to July 2021 were included. Flow cytometry assays were used to study lymphocyte subsets obtained from the bone marrow of the participants as well as changes in natural killer (NK) cell function. One-way analysis of variance and Student's t-test were used to analyze the data. Results: We found a reduction in the number and function of NK cells in patients with MDS. By further measuring the activating and inhibitory receptors on the surface of NK cells, we found that the T cell immunoglobulin and ITIM domain (TIGIT) was the highest expressed marker on NK cells. Additionally, the expression of CD155, which is the ligand of TIGIT, was significantly higher than expressions of CD112 and CD113 on bone marrow mesenchymal stem cells (BMSCs). Conclusions: The co-culture results of BMSCs and NK cells demonstrated that BMSCs regulate NK cells through the TIGIT/CD155 interaction, indicating that NK cells play a vital role in MDS progression. BMSCs regulate the function of NK cells via TIGIT/CD155. EvM_ycHj6U8mjawjepZzLz Video Abstract [ABSTRACT FROM AUTHOR]

Objective: To develop a quantitative Response Evaluation Criteria in Solid Tumors (qRECIST) for evaluating response to neoadjuvant therapy (nT) in ESCCs relying on multiparametric (mp) MRI.Methods: Patients with cT2-T4a/N0-N3/M0 ESCC undergoing pre-nT and post-nT esophageal mpMRI before radical resection were prospectively included. Images were reviewed by two experienced radiologists. qRECIST was redefined using four methods including conventional criterion (cRECIST) and three model-dependent RECIST relying on quantitative MRI measurements at pre-nT, post-nT, and delta pre-post nT, respectively. Pathological tumor regression grades (TRGs) were used as a reference standard. The rates of agreement between four qRECIST methods and TRGs were determined with a Cronbach's alpha test, area under the curve (AUC), and a diagnostic odds ratio meta-analysis.Results: Ninety-one patients were enrolled. All four methods revealed high inter-reader agreements between the two radiologists, with a Kappa coefficient of 0.96, 0.87, 0.88, and 0.97 for cRECIST, pre-nT RECIST, post-nT RECIST, and delta RECIST, respectively. Among them, delta RECIST achieved the highest overall agreement rate (67.0% [61/91]) with TRGs, followed by post-nT RECIST (63.8% [58/91]), cRECIST (61.5% [56/91]), and pre-nT RECIST (36.3% [33/91]). Especially, delta RECIST achieved the highest accuracy (97.8% [89/91]) in distinguishing responders from non-responders, with 97.3% (34/35) for responders and 98.2% (55/56) for non-responders. Post-nT RECIST achieved the highest accuracy (93.4% [85/91]) in distinguishing complete responders from non-pCRs, with 77.8% (11/18) for pCRs and 94.5% (69/73) for non-pCRs.Conclusion: The qRECIST with mpMRI can assess treatment-induced changes and may be used for early prediction of response to nT in ESCC patients.Key Points: • Quantitative mpMRI can reliably assess tumor response, and delta RECIST model had the best performance in evaluating response to nT in ESCCs, with an AUC of 0.98, 0.95, 0.80, and 0.82 for predicting TRG0, TRG1, TRG2, and TRG3, respectively. • In distinguishing responders from non-responders, the rate of agreement between delta RECIST and pathology was 97.3% (34/35) for responders and 98.2% (55/56) for non-responders, resulting in an overall agreement rate of 97.8% (89/91). • In distinguishing pCRs from non-pCR, the rate of agreement between MRI and pathology was 77.8% (11/18) for pCRs and 94.5% (69/73) for non- pCRs, resulting in an overall agreement rate of 91.2% (83/91). [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate an optimal model based on the 1-mm-isotropic-3D contrast-enhanced StarVIBE MRI sequence combined with clinical risk factors for predicting survival in patients with esophageal squamous cell carcinoma (ESCC).Methods: Patients with ESCC at our institution from 2015 to 2017 participated in this retrospective study based on prospectively acquired data, and were randomly assigned to training and validation groups at a ratio of 7:3. Random survival forest (RSF) and variable hunting methods were used to screen for radiomics features and LASSO-Cox regression analysis was used to build three models, including clinical only, radiomics only and combined clinical and radiomics models, which were evaluated by concordance index (CI) and calibration curve. Nomograms and decision curve analysis (DCA) were used to display intuitive prediction information.Results: Seven radiomics features were selected from 434 patients, combined with clinical features that were statistically significant to construct the predictive models of disease-free survival (DFS) and overall survival (OS). The combined model showed the highest performance in both training and validation groups for predicting DFS ([CI], 0.714, 0.729) and OS ([CI], 0.730, 0.712). DCA showed that the net benefit of the combined model and of the clinical model is significantly greater than that of the radiomics model alone at different threshold probabilities.Conclusions: We demonstrated that a combined predictive model based on MR Rad-S and clinical risk factors had better predictive efficacy than the radiomics models alone for patients with ESCC.Key Points: • Magnetic resonance-based radiomics features combined with clinical risk factors can predict survival in patients with ESCC. • The radiomics nomogram can be used clinically to predict patient recurrence, DFS, and OS. • Magnetic resonance imaging is highly reproducible in visualizing lesions and contouring the whole tumor. [ABSTRACT FROM AUTHOR]

• The radiative cooling gray paint (RCGP) with high solar reflectance for thermal management of electronic equipment. • The RCGP on a heat sink module of outdoor base station yields a distinctive temperature drop beyond 10 ℃. • The cooling potential of the RCGP were validated via the simulations and experiment. • The developing directions of colored radiative cooling were pointed out. Colored appearance is an ongoing pursue for the devising of radiative cooling paint (RCP), while the inevitable absorption of solar radiation remains a huge hurdle to meet the threshold of RCP under intense sunlight. Gray is one of the most common color for the equipment appearance in the industrial design, but rarely works have been made to explore the potential of gray radiative cooling paint integrated on the engineering equipment. Herein, we utilize the poly (vinylidene fluoridehexafluoropropylene)-acrylic (PVDF-HFP-PMMA) containing yttria particle and commercial dye to fabricate radiative cooling gray paint (RCGP). The porous structure in paint endows an effective light scattering of sunlight, and the high refractive index and wide bandgap of yttria further promote the reflection of visible light. As a result, the RCGP with a grayscale value of 237 exhibits a high reflectance beyond 0.89 in solar waveband and a high emittance over 0.96 in the atmospheric transparence window (ATW, 8–13 μm). We theoretically and experimentally explore the cooling potential of RCGP on a heat sink module of outdoor base station, yielding a distinctive temperature drop beyond 10 ℃. Our work provides a feasible strategy for minimizing the adverse effect from the color on the reflective property, and makes tentative and significant exploration of radiative cooling in engineering thermal management. [ABSTRACT FROM AUTHOR]

Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis. In this study, we evaluated chimeric antigen receptor (CAR) T cell therapy targeting CLL-1 in adults with R/R AML patients. Patients received conditioning chemotherapy with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days and an infusion of a dose of 1–2 × 106 CAR-T cells/kg. The incidence of dose-limiting toxicity was the primary endpoint. Ten patients were treated, and all developed cytokine release syndrome (CRS); 4 cases were low-grade, while the remaining 6 were considered high-grade CRS. No patient developed CAR-T cell-related encephalopathy syndrome (CRES). Severe pancytopenia occurred in all patients. Two patients died of severe infection due to chronic agranulocytosis. The complete response (CR)/CR with incomplete hematologic recovery (CRi) rate was 70% (n = 7/10). The median follow-up time was 173 days (15–488), and 6 patients were alive at the end of the last follow-up. CAR-T cells showed peak expansion within 2 weeks. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML. [ABSTRACT FROM AUTHOR]