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Monoclonal antibody-based targeted therapies have greatly improved treatment options for patients by binding to the innate immune system. However, the long-term efficacy of such antibodies is limited by mechanisms of drug resistance. Over the last 50 years, with advances in protein engineering technology, more and more bispecific antibody (bsAb) platforms have been engineered to meet diverse clinical needs. Bispecific NK cell engagers (BiKEs) or tri-specific NK cell engagers (TriKEs) allow for direct targeting of immune cells to tumors, and therefore resistance and serious adverse effects are greatly reduced. Many preclinical and clinical trials are currently underway, depicting the promise of antibody-based natural killer cell engager therapeutics. In this review, we compile worldwide efforts to explore the involvement of NK cells in bispecific antibodies. With a particular emphasis on lessons learned, we focus on preclinical and clinical studies in malignancies and discuss the reasons for the limited success of NK-cell engagers against solid tumors, offering plausible new ideas for curing some advanced cancers shortly.

C21H26FNO, orthorhombic, Pna21 (no. 33), a = 12.329(3) Å, b = 9.048(3) Å, c = 16.881(5) Å, β = 90°, V = 1883.2(9) Å3, Z = 4, R gt(F) = 0.0500, wR ref(F 2) = 0.1184, T = 273(2) K.

To promote scientific progress and optimize the utilization of natural plant resources that rich in selenium, the study selected selenium-rich Hibiscus manihot L. as the research object, using the HG-AFS to detect the selenium content in different plant organ samples, ultrasound assisted ethanol extraction of selenium containing organic active components from sunflower flowers, and obtaining the optimal extraction process by response surface methodology. At the same time, conducting antioxidant activity research on selenium containing extracts. The results showed that the total Se concentrations in different organs of Hibiscus manihot L., from highest to lowest were found in the leaves, fruits, flowers, roots, and stems, with concentrations of 21.99, 14.29, 12.93, 10.90, and 10.23 mg/kg, respectively. The RSM optimization results indicated that the ideal conditions for the extraction parameters were as follows: Extraction temperature of 40 °C, solid-liquid ratio of 1:60, extraction time of 40 minutes, ultrasonic power of 350 W, ethanol concentration of 50% (V/V), under one-time extraction. For the optimal conditions, the selenium extraction rate was 36.65%±0.65%. The DPPH antioxidant activity analysis showed a half-inhibitory concentration (IC50) value of 0.048 mg/mL (with a Se concentration of 0.79 μg/mL), the hydroxyl radical scavenging analysis showed that the maximum clearance rate was 97% when the extracts concentration was 8 mg/mL, and the IC50 was 0.56 mg/mL. The reducing power analysis showed that the reducing power of the extracts increases with the increase of the concentration, indicating that the extracts possess a good antioxidant capacity. The present study would provide empirical evidence to support the efficient use of selenium-rich Hibiscus manihot L. and the extraction of selenium-rich agricultural by-products. [ABSTRACT FROM AUTHOR]

Optoelectronic oscillators (OEOs), which have attracted extensive studies in the past decades, are high quality-factor optoelectronic feedback loops for generating various ultra-pure microwave signals. In essence, OEOs are also dissipative nonlinear systems with multiple timescale characteristics and abundant nonlinearities, which open the possibilities for exploring localized dissipative solitary waves. In this paper, we demonstrate a new-class temporal dissipative soliton, i.e., dissipative microwave photonic soliton molecule (DMPSM), in a dual-bandpass OEO. Both the numerical simulation and experiment are conducted to reveal the physical mechanism of DMPSM generation and to evaluate the characteristics of the generated DMPSM sequences. Unlike optical soliton molecules in mode-locked lasers, the formation of DMPSMs arises from the combined action of multiple timescale coupling, nonlinear bistability, and time-delayed feedback in the OEO cavity, where the soliton interval and number in a DMPSM can be well-controlled through varying the multiple timescale variables in the OEO cavity, and the repetition frequency of the DMPSMs can be tuned through changing that of the initially injected perturbation signal. Meanwhile, the generated DMPSM sequence performs with high stability and excellent coherence, which shows enormous application potentials in pulse radar detection, dense microwave comb generation, and neuromorphology. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is a traditional therapeutic regime that focuses on ionizing radiation, however, RT maintains largely palliative due to radioresistance. Factors such as hypoxia, the radiosensitivity of immune cells, and cancer stem cells (CSCs) all come into play in influencing the significant impact of radioresistance in the irradiated tumor microenvironment (TME). Due to the substantial advances in the treatment of malignant tumors, a promising approach is the genetically modified T cells with chimeric antigen receptors (CARs) to eliminate solid tumors. Moreover, CAR-T cells targeting CSC-related markers would eliminate radioresistant solid tumors. But solid tumors that support an immune deserted TME, are described as immunosuppressive and typically fail to respond to CAR-T cell therapy. And RT could overcome these immunosuppressive features; thus, growing evidence supports the combination of RT with CAR-T cell therapy. In this review, we provide a deep insight into the radioresistance mechanisms, advances, and barriers of CAR-T cells in response to solid tumors within TME. Therefore, we focus on how the combination strategy can be used to eliminate these barriers. Finally, we show the challenges of this therapeutic partnership.

The rise of Na‐storage devices has put forward higher requirements for Na‐storage anode materials with large capacity, long service life, and fast rate capability. Mesoporous carbons, either as active materials or as hosts for guest active nanoparticles, are considered as promising electrode materials. However, addressing the issues of their short lifespan resulting from volume variation and the low coulombic efficiency caused by large surface area via a facile porous structure design still remains a challenge. Herein, a versatile phosphorus‐doped mesoporous carbon (PMC) armed is developed by graphene aerogel (GA) (GA@PMC) for hosting Na‐storage active nanoparticles. As a case study, FeSe2 nanoparticles are selectively supported onto this GA@PMC matrix, creating the FeSe2/GA@PMC composite. When employed in typical Na‐storage devices, such as Na‐ion batteries, Na‐ion hybrid capacitors, and Na‐ion based dual‐ion batteries, the FeSe2/GA@PMC electrode consistently demonstrates superior electrochemical performance. In such GA@PMC, the conformal GA can improve the entire conductivity while decreasing the specific surface area that is directly contacting with electrolyte. The interconnected macroporous structure can not only promote the diffusion of Na+ but also buffers the volume change of the guest active nanoparticles. This bespoke carbon platform synergistically endows the electrode material with enhanced rate capability, cyclic stability, and coulombic efficiency, which are being expected in advanced Na‐storage devices. [ABSTRACT FROM AUTHOR]

Tomato is a popular vegetable worldwide; its production is highly threatened by infection with the potato spindle tuber viroid (PSTVd). We obtained the full‐length genome sequence of previously conserved PSTVd and inoculated it on four genotypes of semi‐cultivated tomatoes selected from a local tomato germplasm resource. SC‐5, which is a PSTVd‐resistant genotype, and SC‐96, which is a PSTVd‐sensitive genotype, were identified by detecting the fruit yield, plant growth, biomass accumulation, physiological indices, and PSTVd genome titer after PSTVd inoculation. A non‐target metabolomics study was conducted on PSTVd‐infected and control SC‐5 to identify potential anti‐PSTVd metabolites. The platform of liquid chromatography‐mass spectrometry detected 158 or 123 differential regulated metabolites in modes of positive ion or negative ion. Principal component analysis revealed a clear separation of the global metabolite profile between PSTVd‐infected leaves and control regardless of the detection mode. The potential anti‐PSTVd compounds, xanthohumol, oxalicine B, indole‐3‐carbinol, and rosmarinic acid were significantly upregulated in positive ion mode, whereas echinocystic acid, chlorogenic acid, and 5‐acetylsalicylic acid were upregulated in negative ion mode. Xanthohumol and echinocystic acid were detected as the most upregulated metabolites and were exogenously applied on PSTVd‐diseased SC‐96 seedlings. Both xanthohumol and echinocystic acid had instant and long‐term inhibition effect on PSTVd titer. The highest reduction of disease symptom was induced by 2.6 mg/L of xanthohumol and 2.0 mg/L of echinocystic acid after 10 days of leaf spraying, respectively. A superior effect was seen on echinocystic acid than on xanthohumol. Our study provides a statistical basis for breeding anti‐viroid tomato genotypes and creating plant‐originating chemical preparations to prevent viroid disease. [ABSTRACT FROM AUTHOR]

Aims: To determine the contributions of different kinds of symptoms to the quality of life and mediating effect of psychological and physical symptoms between heart failure symptoms and quality of life. Design: A multi‐centre cross‐sectional study. Methods: 2006 chronic heart failure patients from four cities were recruited in China from January 2021 to December 2022. Patients' symptoms and quality of life were self‐reported, and data were analysed using correlation analysis, dominance analysis and mediating effects analysis. Results: The dominance analysis revealed that the overall mean contributions of heart failure, psychological and physical symptoms were.083,.085 and.111; 29.5%, 30.2% and 39.5% of the known variance. And heart failure symptoms could negatively affect quality of life through psychological and physical symptoms, accounting for 28.39% and 22.95% of the total effect. Heart failure symptoms could also affect quality of life through the chain‐mediated effect of physical and psychological symptoms, accounting for 16.74%. Conclusions: Physiological symptoms had the strongest effect on quality of life and heart failure symptoms had the weakest. Most of the effect for heart failure symptoms on quality of life in chronic heart failure patients was mediated by psychological and physiological symptoms. Relevance to Clinical Practice: It is important to design non‐pharmacological intervention plans for the enhancement of physical and psychological symptoms' management skills, to reduce the adverse impact of heart failure symptoms on quality of life. Reporting Method: Study methods and results reported in adherence to the STROBE checklist. No Patient or Public Contribution: No patients or members of the public were involved in the study. [ABSTRACT FROM AUTHOR]