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BACKGROUND: Chronic pain was associated with a higher risk of mental disorders (e.g., depression and anxiety). However, the role of 24-h movement behaviors in the association remains unclear. METHODS: A total of 72,800 participants with accelerometer data and free of mental disorders from the UK Biobank were analyzed. The compositional mediation model and isotemporal substitution model were used to explore the associations between chronic pain, 24-h movement behaviors, and the incidence of overall mental disorders, depression, and anxiety. RESULTS: With a median follow-up of 13.36 years, participants with chronic pain had a higher rate of incident overall mental disorders (hazard ratio (HR): 1.281, 95% confidence interval (CI): 1.219 to 1.344), anxiety (HR: 1.391, 95% CI: 1.280 to 1.536), and depression (HR: 1.703, 95% CI: 1.551 to 1.871). Increased sedentary behavior (SB) and reduced moderate-to-vigorous physical activity (MVPA) caused by chronic pain both increased the risk of mental disorders. Twenty-four-hour movement behaviors explained the relationship between chronic pain and overall mental disorders, depression, and anxiety by 10.77%, 5.70%, and 6.86%, respectively. Interaction effects were found between MVPA and chronic pain when predicting the incidence of depression and between MVPA, sleep (SLP), and chronic pain when predicting the incidence of mental disorders. People with chronic pain would recommend at least 0.5 h per day of MVPA and 7 h per day of SLP and restricting SB below 11.5 h per day. CONCLUSIONS: Twenty-four-hour movement behaviors played a significant mediating role in the association between chronic pain and mental disorders. Individuals with chronic pain should engage in more MVPA, less sedentary behavior, and have 7-h sleep per day.

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The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization. However, the in vivo distribution and release of siRNA still cannot be effectively monitored. In this study, based on the fluorescence resonance energy transfer (FRET) principle, a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds (Au-DR-siRNA), which were then wrapped with lipid nanoparticles (LNPs) for monitoring the release behaviour of siRNA in vivo. The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells, the fluorescence of Cy5 would change from quenched state to activated state, showing the location and time of siRNA release. Besides, the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds. Therefore, this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA, but also a siRNA delivery system for treating and diagnosing tumors.

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Chimeric receptor T cells (CAR-T) can effectively cure leukemia; however, there are two limitations: a complicated preparation process ex vivo and cytokine release syndrome (CRS). In this study, we constructed a lipid nanoparticle system modified by CD3 antibody on the surface, loading with the plasmid containing the combination gene of interleukin 6 short hairpin RNA (IL-6 shRNA) and CD19-CAR (AntiCD3-LNP/CAR19 + shIL6). The system targeted T cells by the mediation of CD3 antibody and stably transfected T cells to transform them into CAR-T cells with IL-6 knockdown, thus killing CD19-highly expressed leukemia tumor cells and reducing CRS caused by IL-6. In vivo experiments showed that AntiCD3-LNP/CAR19 + shIL6 could stably transfect T cells and produce CAR-T within 90 days to kill the tumor. This significantly prolonged the survival time of leukemia model mice and demonstrated the prepared LNP exhibited the same anti-tumor effect as the traditional CAR-T cells prepared ex vivo. In this study, CAR-T cells were directly produced in vivo after intravenous injection of the lipid nanoparticles, without the need of using the current complex process ex vivo. Additionally, IL-6 expression was silenced, which would be helpful to reduce the CRS and improve the safety of CAR-T therapy. This method improves the convenience of using CAR-T technology and is helpful in further promoting the clinical application of CAR-T.

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With the rapid development of multimedia and Internet technology, English news text summary technology has received widespread attention as a way to quickly obtain English news text content. The existing method of English news text summarization based on graph model usually takes English news text as the vertices of the graph, and the relationship between the two vertices is represented by the edge. Although it has achieved good results, it cannot quickly sort out the English Complex relationships between news texts. In order to solve this problem, this paper uses the hypergraph model to model the relationship between English news text, and conducts in-depth research on the application of the hypergraph model in the field of English news text summarization. The high popularity of the Internet has brought about earth-shaking changes to the news industry, which makes the news on the Internet a great way for netizens to get news. However, the public cannot pick out satisfactory events from a large amount of news. In order to solve this problem, news event discovery technology that can help users quickly discover and understand hot news is produced. In addition, user personalized recommendation technology will rely on customer operation habits to provide customers with hot events of interest. The personalized news recommendation method adopted in this article has the advantages of integrating discovery and personalized news recommendation, and provides users with a better experience. Compared with the traditional hierarchical clustering algorithm, the algorithm proposed in this paper significantly improves the accuracy.

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The rapid evolution of cell-based theranostics has attracted extensive attention due to their unique advantages in biomedical applications. However, the inherent functions of cells alone cannot meet the needs of malignant tumor treatment. Thus endowing original cells with new characteristics to generate multifunctional living cells may hold a tremendous promise. Here, the nanoengineering method is used to combine customized liposomes with neutrophils, generating oxygen-carrying sonosensitizer cells with acoustic functions, which are called Acouscyte/O2 , for the visual diagnosis and treatment of cancer. Specifically, oxygen-carried perfluorocarbon and temoporfin are encapsulated into cRGD peptide modified multilayer liposomes (C-ML/HPT/O2 ), which are then loaded into live neutrophils to obtain Acouscyte/O2 . Acouscyte/O2 can not only carry a large amount of oxygen but also exhibits the ability of long circulation, inflammation-triggered recruitment, and decomposition. Importantly, Acouscyte/O2 can be selectively accumulated in tumors, effectively enhancing tumor oxygen levels, and triggering anticancer sonodynamics in response to ultrasound stimulation, leading to complete obliteration of tumors and efficient extension of the survival time of tumor-bearing mice with minimal systemic adverse effects. Meanwhile, the tumors can be monitored in real time by temoporfin-mediated fluorescence imaging and perfluorocarbon (PFC)-microbubble-enhanced ultrasound imaging. Therefore, the nanoengineered neutrophils, i.e., Acouscyte/O2 , are a new type of multifunctional cellular drug, which provides a new platform for the diagnosis and sonodynamic therapy of solid malignant tumors.

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Diacids are important monomers in the polymer industry to construct valuable materials. Dicarboxylation of unsaturated bonds, such as alkenes and alkynes, with CO2 has been demonstrated as a promising synthetic method. However, dicarboxylation of C─C single bonds with CO2 has rarely been investigated. Herein we report a novel electrochemical ring-opening dicarboxylation of C─C single bonds in strained rings with CO2. Structurally diverse glutaric acid and adipic acid derivatives were synthesized from substituted cyclopropanes and cyclobutanes in moderate to high yields. In contrast to oxidative ring openings, this is also the first realization of an electroreductive ring-opening reaction of strained rings, including commercialized ones. Control experiments suggested that radical anions and carbanions might be the key intermediates in this reaction. Moreover, this process features high step and atom economy, mild reaction conditions (1 atm, room temperature), good chemoselectivity and functional group tolerance, low electrolyte concentration, and easy derivatization of the products. Furthermore, we conducted polymerization of the corresponding diesters with diols to obtain a potential UV-shielding material with a self-healing function and a fluorine-containing polyester, whose performance tests showed promising applications.

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Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic and efficient way to construct complex skeletons, which is dominated by transition-metal catalysis via two electron transfer. Herein, we report a strategy of visible-light photoredox-catalyzed successive single electron transfer, realizing dearomative arylcarboxylation of indoles with CO2. This strategy avoids common side reactions in transition-metal catalysis, including ipso-carboxylation of aryl halides and ß-hydride elimination. This visible-light photoredox catalysis shows high chemoselectivity, low loading of photocatalyst, mild reaction conditions (room temperature, 1 atm) and good functional group tolerance, providing great potential for the synthesis of valuable but difficultly accessible indoline-3-carboxylic acids. Mechanistic studies indicate that the benzylic radicals and anions might be generated as the key intermediates, thus providing a direction for reductive couplings with other electrophiles, including D2O and aldehyde.

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Over the past decades, organometallic complexes with precious elements, such as ruthenium and iridium, are widely used as visible-light photoredox catalysts. Recently, more and more complexes based on earth-abundant and inexpensive elements have been used as sensitizers in photochemistry. Although the photoexcited state lifetimes of iron complexes are typically shorter than those of traditional photosensitizers, the utilization of iron catalysts in photochemistry has sprung up owing to their abundance, low price, nontoxicity, and novel properties, including exhibiting ligand to metal charge transfer states. This concept focuses on recent advances in light-driven iron catalysis in organic transformations, including iron/photoredox dual catalysis, light-induced iron photoredox catalysis and light-induced generation of active iron catalysts. The prospect for the future of this field is also discussed.

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A novel synthesis of five-membered cyclic nitrones has been developed based on the Lewis acid-catalysed [3+2]-annulation reaction of D-A cyclopropanes with 1,4,2-dioxazoles. Broad substrate scope and generally good yield make this reaction useful in the preparation of nitrones. When a suitable 1,4,2-dioxazole was used, nitrone and tetrahydrofuran could be prepared in one pot with high atom economy.

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A Lewis acid catalyzed [3+4]-annulation reaction between cyclopropane 1,1-diesters and anthranils has been developed. This annulation consists of a reaction sequence involving ring-opening/aromatization/nucleophilic addition. Thereinto, aromatization is the driving force for this annulation. Using this reaction, a series of 8-oxa-1-azabicyclo[3.2.1]octanes can be prepared conveniently with excellent diastereoselectivity.