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The enhancement of pesticide utilization efficiency for improved biological activity, while promoting crop growth to enhance disease resistance, holds significant importance in agricultural production. In this study, we developed an enzyme-responsive azoxystrobin (AZOX) delivery system using iron-based mesoporous materials as porous carriers and pectin (Pec) as an encapsulation agent to manage rice sheath blight. The resultant AZOX-AFS-Pec nanoparticles (NPs) exhibit high loading capacity and could intelligently release AZOX in acidic conditions in the presence of pectinase. Notably, AZOX-AFS-Pec NPs demonstrated improved wetting and adhesion properties on rice blades, thereby augmenting AZOX utilization. Furthermore, AZOX-AFS-Pec NPs enhanced fungicidal activity against rice sheath blight, with pot experiments revealing comparable control efficacy on rice sheath blight to AZOX suspension concentration (SC). Specifically, AZOX-AFS-Pec NPs exhibited superior prevention and prolonged protection against rice sheath blight compared to AZOX SC. Additionally, continuous release of Fe2+ and Fe3+ by AZOX-AFS-Pec NPs increased chlorophyll content and promoted rice growth. Moreover, these NPs increased salicylic acid (SA) levels in rice plants, fortifying disease resistance. Importantly, AZOX-AFS-Pec NPs demonstrated over a 2-fold reduction in acute toxicity to earthworms compared to AZOX SC. Therefore, stimuli-responsive AZOX-AFS-Pec NPs show great promise for enhancing pesticide effectiveness against pathogens, improving crop traits, and fortifying disease resistance. [ABSTRACT FROM AUTHOR]

Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106–4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL. [ABSTRACT FROM AUTHOR]

Background: Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients. Methods: From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models. Results: Age, creatinine, neutrophil-to-lymphocyte ratio, and Child–Turcotte–Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633–0.738) and better clinical utility compared with other conventional prognostic models. Conclusions: The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals. [ABSTRACT FROM AUTHOR]

In this paper, a microheater that can absorb thermal stress and has a large heating area is demonstrated by optimizing the structure and process of the microheater. Four symmetrically distributed elongated support beam structures were machined around the microheater via deep silicon etching. This design efficiently mitigates the deformation of the heated region caused by thermal expansion and enhances the structural stability of the microheater. The updated microheater no longer converts the work area into a thin film; instead, it creates a stable heating platform that can uniformly heat a work area measuring 10 × 10 mm2. The microheater is verified to have high temperature uniformity and structural stability in finite element simulation. Finally, thorough investigations of electrical–thermal–structural characterization were conducted. The test findings show that the new microheater can achieve 350 °C with a power consumption of 6 W and a thermal reaction time of 22 s. A scan of its whole plane reveals that the surface of the working area of the new microheater is flat and does not distort in response to variations in temperature, offering good structural stability. [ABSTRACT FROM AUTHOR]

Purpose: To construct and validate a precise and personalized predictive model for non-alcoholic fatty liver disease (NAFLD) to enhance NAFLD screening and healthcare administration.Patients and Methods: A total of 730 participants' clinical information and outcome measurements were gathered and randomly divided into training and validation sets in a ratio of 3:7. Using the least absolute shrinkage and selection operator (LASSO) regression and multiple logistic regression, a nomogram was established to select risk predictor variables. The NAFLD prediction model was validated through the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA).Results: After random grouping, the cohort comprised 517 in the training set and 213 in the validation set. The prediction model employed nine of the 20 selected variables, namely gender, hypertension, waist circumference, body mass index, blood platelet, triglycerides, high-density lipoprotein cholesterol, plasma glucose, and alanine aminotransferase. ROC curve analysis yielded an area under the curve values of 0.877 (95% Confidence Interval [CI]: 0.848– 0.907) for the training set and 0.871 (95% CI: 0.825– 0.917) for the validation set. Optimal critical values were determined as 0.472 (0.786, 0.825) in the training set and 0.457 (0.743, 0.839) in the validation set. Calibration curves for both sets showed proximity to the ideal diagonal, with P-values of 0.972 and 0.370 for the training and validation sets, respectively (P > 0.05). DCA indicated favorable clinical applicability of the model.Conclusion: We constructed a nomogram model that could complement traditional NAFLD detection methods, aiding in individualized risk assessment for NAFLD. [ABSTRACT FROM AUTHOR]

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs)., Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems., Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38 + tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38 + /CD47 + tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice., Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo . As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile., Competing Interests: WT and SL hold ownership interest including patents in ImmuneOnco Biopharmaceuticals Shanghai Inc. Authors SoL, DC, YY, HG, DL, NS, XB, KW, TL, GL, CY, WZ, LZ, GZ, LP, SiL, XT, RZ, and WT were employed by the company ImmuneOnco Biopharmaceuticals Shanghai Inc. The authors declare that this study was funded in its entirety by Immuneonco Biopharmaceuticals (Shanghai) Inc. The funder had the following involvement in the study: study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication., (Copyright © 2024 Li, Chen, Yang, Guo, Liu, Sun, Bai, Wang, Li, Li, Yang, Zhang, Zhang, Zhao, Peng, Liu, Tu, Zhang and Tian.)

Objective: National health is essential for economic and social development. The aim of this article is to examine the relationship, heterogeneity effects and influential mechanisms between National Forest Cities and the residents' health., Methods: The article matches the China Family Panel Studies data in 2018 (CFPS2018) with the 2016-2018 National Forest Cities Construction List, resulting in a final sample of 20,041. Oprobit, Ologit, Instrumental Variable technique (2SLS) and interaction term analysis were used as the main research methods in this article., Results: The findings indicate that: (1) The construction of National Forest Cities significantly improves the residents' health in terms of both physical and mental health, and this conclusion is still valid after a series of robustness tests. (2) On the one hand, National Forest Cities promote residents' health by reducing air pollutants such as SO 2 and soot to reduce residents' health risk exposure; On the other hand, it promotes residents' health by positively guiding them to engage in healthy behaviors. (3) National Forest Cities have a greater effect on the health of urban residents, older adult and lower-income group, suggesting that National Forest Cities are a public benefit., Conclusions: The construction of National Forest Cities is a public welfare that promotes residents' health, and it is an important revelation for accelerating the realization of the Healthy China Strategy. The article provides new empirical evidence for understanding the welfare effects of forest cities and offers new practical paths for improving residents' health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xie, Yang and Tan.)

Here, we report a draft genome sequence of endophytic fungus Phoma sp . strain YAFEF320, isolated from the roots of Gerbera jamesonii . The genome size of Phoma sp. YAFEF320 was 32,542,820 bp with 52.08% GC content. The genome resource will support future research into potential secondary metabolite diversity of this fungus., Competing Interests: The authors declare no conflict of interest.