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Some challenges still exist with single-target B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapies due to variable or negative BCMA expression, although they have yielded remarkable efficacy in relapsed or refractory multiple myeloma. We developed anti-BCMA/GPRC5D bispecific CARs to mitigate the limitations and potentiate the functions of CAR T cells.

To describe the selection, development, and implementation of quality measures (QMs) for juvenile idiopathic arthritis (JIA) by the Pediatric Rheumatology Care and Outcomes Improvement Network (PR‐COIN), a multihospital learning health network using quality improvement methods and leveraging QMs to drive improved outcomes across a JIA population since 2011. An American College of Rheumatology–endorsed multistakeholder process previously selected initial process QMs. Clinicians in PR‐COIN and parents of children with JIA collaboratively selected outcome QMs. A committee of rheumatologists and data analysts developed operational definitions. QMs were programmed and validated using patient data. Measures are populated by registry data, and performance is displayed on automated statistical process control charts. PR‐COIN centers use rapid‐cycle quality improvement approaches to improve performance metrics. The QMs are revised for usefulness, to reflect best practices, and to support network initiatives. The initial QM set included 13 process measures concerning standardized measurement of disease activity, collection of patient‐reported outcome assessments, and clinical performance measures. Initial outcome measures were clinical inactive disease, low pain score, and optimal physical functioning. The revised QM set has 20 measures and includes additional measures of disease activity, data quality, and a balancing measure. PR‐COIN has developed and tested JIA QMs to assess clinical performance and patient outcomes. The implementation of robust QMs is important to improve quality of care. PR‐COIN's set of JIA QMs is the first comprehensive set of QMs used at the point‐of‐care for a large cohort of JIA patients in a variety of pediatric rheumatology practice settings.

This paper uses the new polymer material N-glycyrrhetinic acid (GA)-polyethylene glycol (PEG)-chitosan (NGPC) as the carrier material, and uses the ion cross-linking method to prepare Brucine-loaded chitosan nanoparticles (Brucine/NGPC-NPs). The uptake of Brucine solution and Brucine/NGPC-NPs by hepatocellular carcinoma cells is both time- and concentration-dependent. The uptake of NGPC-NPs is significantly stronger than that of solution. It has significant active transport characteristics, and the intake follows the order of exogenous licorice. The addition of acid decreases, and its uptake pathway mainly depends on clathrin-mediated endocytosis and then internalisation by the cell. Therefore, we can conclude that NGPC-NPs can be used as a carrier for liver cell targeting, significantly increasing the amount of drugs entering liver cancer cells, and achieving the purpose of reducing toxicity and increasing efficiency.

As children mature, bike products for children in the market develop at the same time, and the conditions are frequently updated. Certain problems occur when using a bike, such as cycle overlapping, repeating function, and short life cycle, which go against the principles of energy conservation and the environmental protection intensive design concept. In this paper, a rational multi-function method of design through functional superposition, transformation, and technical implementation is proposed. An organic combination of frog-style scooter and children’s tricycle is developed using the multi-function method. From the ergonomic perspective, the paper elaborates on the body size of children aged 5 to 12 and effectively extracts data for a multi-function children’s bike, which can be used for gliding and riding. By inverting the body, parts can be interchanged between the handles and the pedals of the bike. Finally, the paper provides a detailed analysis of the components and structural design, body material, and processing technology of the bike. The study of Industrial Product Innovation Design provides an effective design method to solve the bicycle problems, extends the function problems, improves the product market situation, and enhances the energy saving feature while implementing intensive product development effectively at the same time.

Different processing methods significantly affect the content of bioactivities and the anti-oxidant activities in food sources, including black rice, one of the world's major food sources of black rice anthocyanin extract (BRAE). In this study, the effect of drum-drying and extrusion processes on lipopolysaccharide (LPS)-induced inflammatory responses by bioactive compounds and antioxidants from black rice extract was determined. This study identified the total phenolic, flavonoid, and anthocyanin contents and antioxidant activities in vitro. The phytochemical constituent analysis of three anthocyanin-enriched extracts from raw (BRAE), drum-dried (D-BRAE), and extruded black rice (E-BRAE) using UPLC-LTQ-Orbitrap-MS/MS tentatively identified nine compounds. Cyanidin-3-glucoside was the major anthocyanin in black rice extracts. In contrast, significant reduced levels of cyanidin-3-glucoside and peonidin-3-glucoside were found in D-BRAE and E-BRAE, and the content of protocatechuic acid was increased obviously in E-BRAE. The anti-inflammatory effects of differently processed rice extracts in LPS-stimulated RAW264.7 cells demonstrated that BRAE, D-BRAE, and E-BRAE (400 μg/mL) significantly inhibited NO and PGE2 secretion (p < 0.001) by down-regulating iNOS and COX-2 mRNA and protein expression levels. mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) were also decreased by BRAE, D-BRAE, and E-BRAE. Therefore, the anti-inflammatory activities of BRAE were not affected by drum-dried or extrusion process. Activation of MAPK and NF-κB pathways were inhibited by BRAE that influenced the regulation of the phosphorylation of JNK, ERK, p65, and IκBα. These pathways were not affected by the drum-dried process but were significantly enhanced by the extrusion process. This study will provide scientific and meaningful basics for the application of BRAE using different processing methods in anti-oxidant and anti-inflammation.

Objective: Extracellular vesicles (Evs) secreted from cells have been revealed to mediate signal transduction between cells. Nevertheless, the mechanisms through which molecules transported by EVs function remain to be elucidated. In the present study, the functional relevance of endothelial cells (ECs)-secreted Evs carrying microRNA-376c (miR-376c) in the biological activities of non-small cell lung cancer (NSCLC) cells was investigated, including the related mechanisms.Methods: Two cell lines with the highest YTH N6-methyladenosine (m6A) RNA binding protein 1 (YTHDF1) expression were selected for subsequent experiments. Cellular proliferation, migration, invasion and apoptosis were measured by EdU, wound healing, Transwell assays and flow cytometry, respectively. The binding relationship between miR-376c and YTHDF1 was analyzed by dual-luciferase reporter assays. The miR-376c, YTHDF1 and β-catenin expression was evaluated by qPCR assays and western blot assays.Results: The expression patterns of YTHDF1 were higher in NSCLC cells, whereas miR-376c was reduced versus the normal bronchial epithelial cells. Silencing of YTHDF1 repressed NSCLC cell proliferation, invasion and migration abilities, whereas enhanced apoptosis. miR-376c negatively modulated YTHDF1 expression. Under co-culture conditions, ECs transmitted miR-376c into NSCLC cells through Evs, and inhibited the intracellular YTHDF1 expression and the Wnt/β-catenin pathway activation. Rescue experiments revealed that YTHDF1 overexpression reversed the inhibitory role of miR-376c released by EC-Evs in NSCLC cells.Conclusion: EC-delivered Evs inhibit YTHDF1 expression and the Wnt/β-catenin pathway induction via miR-376c overexpression, thus inhibiting the malignant phenotypes of NSCLC cells.

Objective: Although microRNA-103a (miR-103a) dysfunction has been implicated in various cancers, its relevance to non-small cell lung cancer (NSCLC) has not been clarified. This study was conducted to examine the molecular mechanism underlying the regulatory role of miR-103a in NSCLC.Methods: Kaplan–Meier analysis was carried out to assess the relationship between overall survival of NSCLC patients and miR-103a expression. Reverse-transcription quantitative polymerase chain reaction and western blot analyses were applied to evaluate the expression of relevant genes in tissues and cells. Sphere formation, MTS, flow cytometry, and Transwell assays were performed to characterize stemness. Dual luciferase reporter gene assays were used to clarify the binding relationship between miR-103a and ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1). Finally, western blot analysis was used to assess the involvement of the Hippo pathway in NSCLC.Results: In NSCLC tissues and cells, miR-103a was expressed at low levels, whereas OTUB1 was expressed at high levels. Higher miR-103 expression levels were associated with a better prognosis for patients with NSCLC. When miR-103a was overexpressed, cell viability and stemness decreased, whereas apoptosis and cell cycle arrest were facilitated. The expression of phosphorylated YAP also decreased significantly. Opposite trends were observed after miR-103a silencing. OTUB1 expression and YAP phosphorylation decreased in the presence of miR-103a, and OTUB1 overexpression blocked the inhibitory effects of miR-103a on NSCLC cells.Conclusion: The miR-103a/OTUB1/Hippo axis may play a role in modulating the malignant behavior and stemness of cancer stem cells and thus could be a potential therapeutic target for the management of NSCLC.