Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, a red blood cell membrane (mRBC)‐camouflaged hollow MnO2 (HMnO2) catalytic nanosystem ...embedded with lactate oxidase (LOX) and a glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion as well as synergistic metabolic therapy and immunotherapy of tumor. Benefiting from the long‐circulation property of the mRBC, the nanosystem can gradually accumulate in a tumor site through the enhanced permeability and retention (EPR) effect. The extracellular nanosystem consumes lactic acid in the TME by catalyzing its oxidation reaction via LOX. Meanwhile, the intracellular nanosystem releases the glycolysis inhibitor to cut off the source of lactic acid, as well as achieve antitumor metabolic therapy through the blockade of the adenosine triphosphate (ATP) supply. Both the extracellular and intracellular processes can be sensitized by O2, which can be produced during the decomposition of endogenous H2O2 catalyzed by the PMLR nanosystem. The results show that the PMLR nanosystem can ceaselessly remove lactic acid, and then lead to an immunocompetent TME. Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti‐PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.
A strategy based on intra/extracellular lactic acid exhaustion is reported to achieve synergistic metabolic therapy and immunotherapy of tumors. This strategy is performed by a cascade catalytic nanosystem (PMLR) that integrates a hollow MnO2 nanocarrier with lactate oxidase and a glycolysis inhibitor.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims
The objective of this study is to explore the various latent categories within the sleep quality of night shift nurses and to investigate whether shift‐related factors predispose nurses to ...higher levels of occupational stress and anxiety.
Design
This is a cross‐sectional study.
Methods
From November to December 2020, registered nurses from 18 tertiary hospitals and 16 secondary hospitals in Chongqing were selected through convenience sampling for this study. Latent class analysis was used to investigate the sleep quality of nurses working night shifts. Furthermore, univariate analysis and logistic multivariate analysis were utilized to identify the contributing factors to occupational stress and anxiety.
Results
The four latent categories of Pittsburgh Sleep Quality Index for night shift nurses were identified as ‘Low Sleep Disorder Group’ (56.34%), ‘Moderate Sleep Disorder Group’ (37.27%), ‘High Sleep Disorder Non‐Reliant on Sleeping medication Group’ (4.89%) and ‘High Sleep Disorder Reliant on Sleeping medication Group’ (1.50%). The results showed that having a night‐shift frequency of 3–4 times per month, night‐shift durations of 9–12 h, sleep time delay after night shift (≥2 h), total sleep time after night shift less than 4 h were shift‐related factors that increased the levels of occupational stress and anxiety.
Conclusion
The sleep quality of night shift nurses demonstrates heterogeneity and can be classified into four latent categories. Higher frequency of night shifts, extended work hours and insufficient rest time are all associated with increased levels of occupational stress and anxiety.
Impact
By identifying the four latent categories of sleep quality among night shift nurses, this study sheds light on the relationship between sleep patterns and levels of occupational stress and anxiety. These findings have important implications for healthcare institutions in the management of nurse well‐being and work schedules.
Patient or Public Contribution
No patient or public contribution.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in ...mammals, an aggressive man‐made RBC (AmmRBC) is created to combat the hypoxia‐mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme‐mimicking polydopamine, and polydopamine‐carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes. The mean corpuscular hemoglobin of AmmRBCs reaches about tenfold as high as that of natural RBCs. Owing to the same origin of outer membranes, AmmRBCs share excellent biocompatibility with parent RBCs. The introduced polydopamine plays the role of the antioxidative enzymes existing inside RBCs to effectively prevent the oxygen‐carrying hemoglobin from the oxidation damage during the circulation. This biomimetic engineering can accumulate in tumors, permit in situ efficient oxygen supply, and impose strong PDT efficacy toward the extremely hypoxic tumor with complete tumor elimination. The man‐made pseudo‐RBC shows potentials as a universal oxygen‐self‐supplied platform to sensitize hypoxia‐limited tumor treatment means, including but not limited to PDT. Meanwhile, this study offers ideas to the production of artificial substitutes of packed RBCs for clinical blood transfusion.
Aggressive man‐made pseudo‐red blood cells (AmmRBCs) are prepared for self‐oxygen‐supplied photodynamic therapy (PDT) toward tumors. AmmRBCs can accumulate in tumors and exhibit high efficacy to combat hypoxia‐induced resistance of tumors to PDT, leading to complete tumor elimination.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Surface modification of nanomaterials is essential for their biomedical applications owing to their passive immune clearance and damage to reticuloendothelial systems. Recently, a cell ...membrane‐coating technology has been proposed as an ideal approach to modify nanomaterials owing to its facile functionalized process and good biocompatibility for improving performances of synthetic nanomaterials. Here, recent advances of cell membrane‐coated nanomaterials are reviewed based on the main biological functions of the cell membrane in living cells. An overview of the cell membrane is introduced to understand its functions and potential applications. Then, the applications of cell membrane‐coated nanomaterials based on the functions of the cell membrane are summarized, including physical barrier with selective permeability and cellular communication via information transmission and reception processes. Finally, perspectives of biomedical applications and challenges about cell membrane‐coated nanomaterials are discussed.
Recent advances of cell membrane‐coated nanomaterials are summarized here based on the main biological functions of the cell membrane, including physical barrier and cellular communication. Perspectives of biomedical applications and challenges of cell membrane‐coated nanomaterials are also discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and ...traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co‐stimulatory molecules for robust immunotherapy. FMs share the tumor's self‐targeting character with the parent cancer cells. In bilateral tumor‐bearing mouse models, the FM‐coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post‐nanophotosensitizer‐induced photodynamic therapy (PDT). The FM‐induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy‐caused regression of the irradiation‐free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor‐specific immunotherapy‐based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.
Using the cytomembranes of fused cells derived from tumor and dendritic cells, a tumor‐specific immunotherapeutic platform is engineered, which is capable of easy cooperation with other therapy means. The hybrid‐cytomembrane‐coated nanophotosensitizer demonstrates durable immunotherapy against primary tumors post‐photodynamic‐therapy (PDT) and PDT‐enhanced immunity toward irradiation‐free distant tumors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and ...advanced immunotherapy. Here, a multifunctional biomimetic core–shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH‐sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir. Murine melanoma cell membrane coating on the core provides tumor targeting ability and elicits an immune response due to abundance of antigens. It is demonstrated that this biomimetic core–shell nanoplatform with oxygen generation can be partial to accumulate in tumor and downregulate the expression of hypoxia‐inducible factor 1α, which can further enhance the therapeutic effects of chemotherapy and reduce the expression of programmed death ligand 1 (PD‐L1). Combined with immune checkpoints blockade therapy by programmed death 1 (PD‐1) antibody, the dual inhibition of the PD‐1/PD‐L1 axis elicits significant immune response and presents a robust effect in lengthening tumor recurrent time and inhibiting tumor metastasis. Consequently, the multifunctional nanoplatform provides a potential strategy of synergetic chemotherapy and immunotherapy.
This work demonstrates a multifunctional biomimetic nanoplatform for reduced tumor chemoresistance and dual inhibition of programmed death 1/programmed death ligand 1 axis by the means of downregulating the expression of hypoxia‐inducible factor 1α, which elicits a significant immune response and presents a robust effect in lengthening tumor recurrence time and inhibiting tumor metastasis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re‐educate immune cells to protect the host. However, the functions of NK cells are often limited in ...the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re‐education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H2O2). The generated H2O2 is also similar to cytokines and chemokines for recruiting immune cells and re‐educating survived macrophages to attack tumor cells. In addition, the oxygen‐carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.
Artificial natural killer (NK) cells are constructed with minor limitations of the immunosuppressive tumor microenvironment for specific tumor killing and renegade macrophage re‐education. The artificial NK cells exhibit efficient tumor inhibition and immune activation as a new sight to overcome tumors by simulating the functions of immune cells.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Increased crop yields are required to support rapid population growth worldwide. Grain weight is a key compo- nent of rice yield, but the underlying molecular mechanisms that control it remain ...elusive. Here, we report the clon- ing and characterization of a new quantitative trait locus （QTL） for the control of rice grain length, weight and yield. This locus, GL3.1, encodes a protein phosphatase kelch （PPKL） family -- Ser/Thr phosphatase. GL3.1 is a member of the large grain WY3 variety, which is associated with weaker dephosphorylation activity than the small grain FAZ1 variety. GL3.I-WY3 influences protein phosphorylation in the spikelet to accelerate cell division, thereby re- suiting in longer grains and higher yields. Further studies have shown that GL3.1 directly dephosphorylates its sub- strate, Cyclin-TI;3, which has only been rarely studied in plants. The downregulation of Cyclin-T1;3 in rice resulted in a shorter grain, which indicates a novel function for Cyclin-T in cell cycle regulation. Our findings suggest a new mechanism for the regulation of grain size and yield that is driven through a novel phosphatase-mediated process that affects the phosphorylation of Cyclin-T1;3 during cell cycle progression, and thus provide new insight into the mechanisms underlying crop seed development. We bred a new variety containing the natural GL3.1 allele that demonstrated increased grain yield, which indicates that GL3.1 is a powerful tool for breeding high-yield crops.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed ...cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.
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