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Tumour heterogeneity remains a major challenge in cancer therapy owing to the different susceptibility of cells to chemotherapy within a solid tumour. Cancer stem-like cells (CSCs), which reside in hypoxic tumour regions, are characterized by high tumourigenicity and chemoresistance and are often responsible for tumour progression and recurrence. Here we report a nanotherapeutic strategy to kill CSCs in tumours using nanoparticles that are co-loaded with the differentiation-inducing agent, all-trans retinoic acid, and the chemotherapeutic drug, camptothecin. All-trans retinoic acid is released under hypoxic conditions, leading to CSC differentiation in the hypoxic niche. In differentiating CSC, the reactive oxygen species levels increase, which then causes the release of camptothecin and subsequent cell death. This dual strategy enables controlled drug release in CSCs and reduces stemness-related drug resistance, enhancing the chemotherapeutic response. In breast tumour mouse models, treatment with the nanoparticles suppresses tumour growth and prevents post-surgical tumour relapse and metastasis.Chemoresistant cancer stem-like cells (CSCs) can be selectively killed by a nanoparticle, which releases an agent under hypoxic conditions that induces CSC differentiation, and a chemotherapeutic drug in response to reactive oxygen species in differentiating CSCs.

Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours. Neutrophils carrying drug-containing liposomes can suppress recurrence of brain tumours after surgical removal of the tumour.

Protein drugs have attracted more attentions due to their high specificity and efficacy. However, the poor stability, plasma degradation, inferior cell membrane permeability, and immunogenicity severely limit the in vivo application of protein drugs. Nanogels are the nanosized crosslinked gels with high water‐loading capacities and large cavities for protein loading, which are able to increase the stability and decrease the immunogenicity for protein delivery. The bioresponsive nanogels possess the capability of programmatically releasing the protein drugs in an on‐demand manner at the target sites with distinct biosignals, which show considerable potential to increase the therapeutic efficacies and decrease the adverse effects of the protein drugs. In this review, we outline the recent advance in the bioresponsive nanogels for delivery of protein drugs, and survey the design of new materials and formulations that can respond typical biosignals, such as temperature, pH, reductive potential, and enzyme expression. The prospects and challenges are also discussed. The bioresponsive nanogels show considerable potential to enhance the therapeutic efficacies and reduce the adverse effects of the protein drugs. This mini‐review summarizes recent advance in the applications of the bioresponsive nanogels for protein delivery and disease treatment.

Laser space networks are an important development direction for inter-satellite communication. Detecting the angle of arrival (AOA) of multiple satellites in a wide field of view (FOV) is the key to realize inter-satellite laser communication networking. The traditional AOA detection method based on the lens system has a limited FOV. In this paper, we demonstrate a system that uses a spatially distributed sensor array to detect the AOA in a wide FOV. The basic concept is to detect AOA using the signal strength of each sensor at different spatial angles. An AOA detection model was developed, and the relationship of key structural parameters of the spatially distributed sensor array on the FOV and angular resolution was analyzed. Furthermore, a spatially distributed sensor array prototype consisting of 5 InGaAs PIN photodiodes distributed on a 3D-printed structure with an inclination angle of 30° was developed. In order to improve the angle calculation accuracy, a multi-sensor data fusion algorithm is proposed. The experimental results show that the prototype’s maximum FOV is 110°. The root mean square error (RMSE) for azimuth is 0.6° within a 60° FOV, whereas the RMSE for elevation is 0.67°. The RMSE increases to 1.1° for azimuth and 1.7° for elevation when the FOV expands to 110°. The designed spatially distributed sensor array has the advantages of a wide FOV and low size, weight, and power (SWaP), presenting great potential for multi-satellite laser communication applications.

Sonic hedgehog (SHH) and heat shock protein 90β (HSP90β) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90β is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90β ubiquitylation through deubiquitylase USP31, thus preventing HSP90β degradation and promoting hepatic lipid synthesis. HSP90β significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90β axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90β-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker. The mechanistic involvement of sonic hedgehog signaling in nonalcoholic steatohepatitis is not clear. Here, the authors show that sonic hedgehog protein regulates the stability of HSP90β, enabling hepatocytes to secrete exosomes containing miR-28-5-p to promote NASH development.

Measurement of the degree of polarization of backscattering light from rough surfaces plays an important role in targets-detection applications. The polarization bidirectional reflectance function is the key to establish the relation between the polarization states of incidence and backscattering light. For the purpose of obtaining a polarized bidirectional reflectance distribution function (pBRDF) of a realistic, complicated target, it is decomposed as typical geometric surfaces and analytically calculated as the degree of polarization of the backscattering light, using a microfacet model, under conditions in which the scale of the target is far less than the target distance. In an experiment testing several typical geometric models, the results coincided with the theoretical calculation. The degree of polarization varied substantially as the rotation angle of the target changed, but showed little dependence on the size of target. The results have potential in applications discriminating between targets at different spatial orientations.

Obesity plays a primary causative role in insulin resistance and hyperglycemia that contributes to type 2 diabetes. Excess lipid storage in the liver renders activation of the resident macrophages and chronic secretion of inflammatory mediators, therefore causing or aggravating insulin resistance. Herein, we develop collaborative assemblies using a “one-pot” synthesis method for macrophage-specific delivery of small interfering RNAs (siRNAs) that target the inflammatory proteins. Ternary nanocomplex (NC) composed of the siRNA molecule, a synthetic thiol-bearing methacrylated hyaluronic acid (sm-HA) and protamine forms through an electrostatic-driven physical assembly, which is chemically crosslinked to acquire the collaboratively assembled nanocapsule (cNC) concurrently. The obtained cNC displays significantly higher stability than NC. Functional moieties as flexible assembly units can be easily equipped on cNC for long circulation, active targeting, or controlled siRNA release. cNC-F decorated with folic acid, a macrophage-targeting ligand promotes the siRNA accumulation in the activated macrophages in the liver of the obese mouse model. cNC-F loaded with siRNA targeting inflammatory indicators efficiently control the macrophage inflammatory response by reducing the expression of the inflammatory proteins (> 40% reduction) and ameliorating the insulin resistance symptoms of the obese mice.

Background The COVID-19 pandemic wreaked havoc on long-term care facilities (LTCFs). Some LTCFs performed better than others at slowing COVID-19 transmission. Emerging literature has mostly described infection prevention and control strategies implemented by LTCFs during the pandemic. However, there is a need for a comprehensive review of factors that influenced the performance of LTCFs in containing COVID-19 spread to inform public health policy. Objective To build on the existing literature, we conducted a scoping review of factors that influenced LTCF performance during the COVID-19 pandemic using a multidimensional conceptual framework of performance. Methods We followed the Joanna Briggs Institute’s methodology for scoping reviews. We queried CINAHL, MEDLINE (Ovid), CAIRN, Science Direct, Scopus, and Web of Science for peer-reviewed literature in English or French published between January 1 st , 2020 and December 31 st , 2021. Retrieved records were screened for context (COVID-19 pandemic), population (LTCFs), interest (internal and external factors that influenced LTCF performance), and outcomes (dimensions of performance: equity, accessibility, reactivity, safety, continuity, efficacy, viability, efficiency). Descriptive characteristics of included articles were summarized. Dimensions of performance as well as internal (e.g., facility characteristics) and external (e.g., visitors) factors identified to have influenced LTCF performance were presented. Results We retained 140 articles of which 68% were classified as research articles, 47% originated in North America, and most covered a period between March and July 2020. The most frequent dimensions of performance were “efficacy” (75.7%) and “safety” (75.7%). The most common internal factors were “organizational context” (72.9%) and “human resources” (62.1%), and the most common external factors were “visitors” (27.1%) and “public health guidelines” (25.7%). Conclusions Our review contributes to a global interest in understanding the impact of the COVID-19 pandemic on vulnerable populations residing and working in LTCFs. Though a myriad of factors were reported, a lack of randomized controlled trials makes it impossible to establish causality between the identified factors and LTCF performance. The use of a multidimensional framework can be recommended to evaluate healthcare system performance not merely in terms of efficacy and safety, but alongside other critical dimensions such as efficiency and equity. Trial registration Research Registry ID: researchregistry7026

USP21 is a ubiquitin specific protease that catalyzes protein deubiquitination, however the identification of its physiological substrates remains challenging. USP21 is known to deubiquitinate transcription factor GATA3 and death-domain kinase RIPK1 in vitro, however the in vivo settings where this regulation plays a biologically significant role remain unknown. In order to determine whether USP21 is an essential and non-redundant regulator of GATA3 or RIPK1 activity in vivo, we characterized Usp21-deficient mice, focusing on mouse viability and development, hematopoietic stem cell function, and lymphocyte differentiation. The Usp21-knockout mice were found to be viable and fertile, with no significant dysmorphology, in contrast to the GATA3 and RIPK1 knockout lines that exhibit embryonic or perinatal lethality. Loss of USP21 also had no effect on hematopoietic stem cell function, lymphocyte development, or the responses of antigen presenting cells to TLR and TNFR stimulation. GATA3 levels in hematopoietic stem cells or T lymphocytes remained unchanged. We observed that aged Usp21-knockout mice exhibited spontaneous T cell activation, however this was not linked to altered GATA3 levels in the affected cells. The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation. The Usp21-deficient mouse line characterized in this study may serve as a useful tool for the future characterization of USP21 physiological functions.

Cancer immunotherapy aims to utilize the host immune system to kill cancer cells. Recent representative immunotherapies include T-cell transfer therapies, such as chimeric antigen receptor T cell therapy, antibody-based immunomodulator therapies, such as immune checkpoint blockade therapy, and cytokine therapies. Recently developed therapies leveraging engineered cells for immunotherapy against cancers have been reported to enhance antitumor efficacy while reducing side effects. Such therapies range from biologically, chemically and physically -engineered cells to bioinspired and biomimetic nanomedicines. In this review, advances of engineering cells for cancer immunotherapy are summarized, and prospects of this field are discussed.