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There is an unmet need for easy‐to‐visualize drug carriers that can deliver therapeutic cargoes deep into solid tumors. Herein, we report the preparation of ultrasmall luminescent imine‐based lanthanide nanocages, Eu60 and Tb60 (collectively Ln60), designed to encapsulate anticancer chemotherapeutics for tumor therapy. The as‐prepared nanocages possess large cavities suitable for the encapsulation of doxorubicin (DOX), yielding DOX@Ln60 nanocages with diameters around 5 nm. DOX@Ln60 are efficiently internalized by breast cancer cells, allowing the cells to be visualized via the intrinsic luminescent property of Ln(III). Once internalized, the acidic intracellular microenvironment promotes imine bond cleavage and the release of the loaded DOX. DOX@Ln60 inhibits DNA replication and triggers tumor cell apoptosis. In a murine triple negative breast cancer (TNBC) model, DOX@Ln60 was found to inhibit tumor growth with negligible side effects on normal tissues. It proved more effective than various controls, including DOX and Ln60. The present nanocages thus point the way to the development of precise nanomedicines for tumor imaging and therapy. [ABSTRACT FROM AUTHOR]

Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single‐cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single‐cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell–cell signaling. In doing so, TB‐related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states. [ABSTRACT FROM AUTHOR]

Nanomedicine shows remarkable potential to improve the efficacy of diagnosis and treatment of tumors, utilizing nanotechnologies and nanomaterials. Gold nanoclusters (AuNCs) have emerged as a highly promising option due to their exceptional optical and enzyme‐mimicking catalytic activities as well as good biocompatibility. The renal clearable clusters can enrich in the tumors upon their enhanced permeability and retention properties, which benefits the tumor‐related applications. The fluorescence of AuNCs in the second near‐infrared region possesses extraordinary penetration depth and high temporal–spatial resolution, enabling excellent in vivo imaging and real‐time monitoring of pathological process. AuNC‐based nanoplatforms represent a paradigm of integrated, efficient, intelligent, and safe treatment strategy, extending personalized tumor therapy. Meanwhile, the optical and biocatalytic properties can be modulated by adopting the atom/ligand engineering, which further enhances the efficacy of AuNCs. Herein, the advances of AuNCs in the field of diagnosis and treatment of tumors are summarized and the directions to be improved are proposed to promote the clinical translation of the AuNCs. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a highly fatal gynecological malignancy due to its high metastasis and recurrence rate. Circular RNA (circRNA) has been regarded as a regulator of CC. However, the underlying molecular mechanism of circ_0005615 in CC remains unclear. The levels of circ_0005615, miR‐138‐5p, and lysine demethylase 2A (KDM2A) were measured using qRT‐PCR or western blot. Cell proliferation was assessed by Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine, and colony formation experiments. Cell invasion and migration were tested by transwell assay and wound healing assay. Flow cytometry and Caspase‐Glo 3/7 Assay kit were used to analyze cell apoptosis. The expression of proliferation‐related and apoptosis‐related markers was detected by western blot. The binding relationships among circ_0005615, miR‐138‐5p, and KDM2A were verified by dual‐luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was applied to detect the effect of circ_0005615 in vivo. Circ_0005615 and KDM2A were upregulated, while miR‐138‐5p was downregulated in CC tissues and cells. Circ_0005615 knockdown retarded cell proliferation, migration, and invasion, while promoting apoptosis. Besides, circ_0005615 sponged miR‐138‐5p, and miR‐138‐5p could target KDM2A. miR‐138‐5p inhibitor reversed the regulation of circ_0005615 knockdown on CC cell growth and metastasis, and KDM2A overexpression also abolished the inhibitory effect of miR‐138‐5p on CC cell growth and metastasis. In addition, we also discovered that circ_0005615 silencing inhibited CC tumor growth in vivo. Circ_0005615 acted as a tumor promoter in CC by regulating the miR‐138‐5p/KDM2A pathway. Highlights: Circ_0005615 was highly expressed in cervical cancer (CC).Knockdown of circ_0005615 inhibited growth and metastasis in CC cells.Circ_0005615 modulated KDM2A expression by sponging miR‐138‐5p. [ABSTRACT FROM AUTHOR]

With an increasingly aging society, bone defects and fractures have become significant threats to human health and quality of life. Currently, autologous and allogeneic bone grafts remain the "gold standard" for the clinical treatment of bone repair. However, bone transplantation is still clinically insufficient, owing to its substantial limitations, such as graft rejection, donor functional defects, and risk of infection. Therefore, a variety of biomaterials have been developed to facilitate bone repair. With the advancement of bone tissue engineering, the focus of research has transitioned from bioinert to bioactive biomaterials. However, many biomaterials have not achieved satisfactory therapeutic effects. In recent years, advancements in osteoimmunology have revealed that the immune system, of which macrophages are critical components, plays an essential regulatory role in bone regeneration. In this review, the role of macrophages in bone healing is explored and recent developments in biomaterials that promote bone regeneration by modulating macrophage polarization and improving the osteoimmune microenvironment are reviewed. This review provides a reference for the development and clinical application of bone repair biomaterials from the immunomodulation perspective. [ABSTRACT FROM AUTHOR]

To sum up, Bcl-3 was decreased during BMSCs senescence, and the supply of Bcl-3 could protect BMSCs from aging. Skeletal aging is characterized by progressive bone loss and increased marrow adiposity.1,2 Age-related bone loss impairs the exercise activity of patients and increases the risk of fracture. (F) Bcl-3, Ac-K49- -catenin and -catenin were analysed by immunoblot in control and Bcl-3-knockdown BMSCs after treated with Wnt 3a for 0 h or 4 h. (G) The levels of Bcl-3 in nuclear and cytoplasmic. B-cell lymphoma-3 controls mesenchymal stem cell commitment and senescence during skeletal aging. [Extracted from the article]

Teriparatide, also known as 1-34 parathyroid hormone (PTH (1-34)), is commonly used for the treatment of osteoporosis in postmenopausal women. But its therapeutic application is restricted by poor metabolic stability, low bioavailability, and rapid clearance. Herein, PTHG2, a glycosylated teriparatide derivative, is designed and synthesized to improve PTH stability and exert more potent antiosteoporosis effect. Surface plasmon resonance (SPR) analysis shows that PTHG2 combines to PTH 1 receptor. Additional acetylglucosamine covalent bonding in the first serine at the N terminal of PTH (1-34) improves stability and increases protein hydrolysis resistance. Intermittent administration of PTHG2 preserves bone quality in ovariectomy- (OVX-) induced osteoporosis mice model, along with increased osteoblastic differentiation and bone formation, and reduced marrow adipogenesis. In vitro, PTHG2 inhibits adipogenic differentiation and promotes osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs). For molecular mechanism, PTHG2 directs BMSCs fate through stimulating the cAMP-PKA signaling pathway. Blocking PKA abrogates the pro-osteogenic effect of PTHG2. In conclusion, our study reveals that PTHG2 can accelerate osteogenic differentiation of BMSCs and inhibit adipogenic differentiation of BMSCs and show a better protective effect than PTH (1-34) in the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Student engagement not only improves student achievement but also affects the dropout rate. Positive classroom interaction between teachers and students enhances student engagement. The interaction between teachers and students is bidirectional, and student engagement can also affect teachers' classroom teaching behavior. Both student engagement and classroom interaction are multidimensional structures, and each dimension is interrelated and mutually influenced. The purpose of this study was to explore the relationship between perceived mathematics classroom interaction and various dimensions of student engagement. In this study, we recruited 1298 students from grades three to five and seven to eight from 36 classes and 15 schools in China participating in a web‐based survey. The results show that cognitive engagement is positively related to behavioral engagement, and emotional support, classroom organization and instructional support play a mediating role between cognitive engagement and behavioral engagement; Emotional engagement is positively related to behavioral engagement, and emotional support and instructional support play a mediating role between emotional engagement and behavioral engagement. Highlights: This study studies the interaction mechanism between classroom interaction and student engagement from a new perspective, breaks through the previous theoretical limitations, and provides suggestions for better promoting student engagement. [ABSTRACT FROM AUTHOR]

In order to improve the effect of intensive care, this paper proposes a lean nursing intervention method and evaluates the lean nursing intervention through a controlled experiment. According to the actual situation of intensive care, this paper starts with the research from several aspects of patients' ICU nursing time, patients' satisfaction, patients' pathological knowledge familiarity, patients' autonomous nursing, and enthusiasm of patients and their families. Moreover, this paper collects and displays experimental results through mathematical statistics, gives patients lean management concepts and methods based on routine care, and finds that it has good management effects. Thus, lean management concepts and methods can effectively improve the anxiety state of critically ill patients, improve the patient's knowledge of disease, and reduce adverse nursing events to improve patient nursing satisfaction, which is worthy of further promotion in the clinic. [ABSTRACT FROM AUTHOR]

Palette‐based image decomposition has attracted increasing attention in recent years. A specific class of approaches have been proposed basing on the RGB‐space geometry, which manage to construct convex hulls whose vertices act as palette colors. However, such palettes do not guarantee to have the representative colors which actually appear in the image, thus making it less intuitive and less predictable when editing palette colors to perform recoloring. Hence, we proposed an improved geometric approach to address this issue. We use a polyhedron, but not necessarily a convex hull, in the RGB space to represent the color palette. We then formulate the task of palette extraction as an optimization problem which could be solved in a few seconds. Our palette has a higher degree of representativeness and maintains a relatively similar level of accuracy compared with previous methods. For layer decomposition, we compute layer opacities via simple mean value coordinates, which could achieve instant feedbacks without precomputations. We have demonstrated our method for image recoloring on a variety of examples. In comparison with state‐of‐the‐art works, our approach is generally more intuitive and efficient with fewer artifacts. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignancies with high levels of invasiveness, drug resistance and mortality, but the internal mechanisms of CRC are largely unknown. MicroRNAs (miRs) have been reported to be involved in the development of CRC, and numerous studies have demonstrated that the abnormal expression of miR‐33a‐5p might be associated with CRC. However, the function and downstream mechanism of miR‐33a‐5p in colorectal cancer (CRC) remains unclear. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme involved in folic acid metabolism, interestingly was confirmed to be one of the target genes of miR‐33a‐5p in the present study. We first confirmed that miR‐33a‐5p in CRC tissues and cell lines were downregulated (P < 0.05), and that the proliferation, clone formation capacities, G1/S progression, and migration capacities of the two CRC cell lines HCT116 cells and HT29 were suppressed by miR‐33a‐5p overexpression in vitro (P < 0.05). Ctrl HCT116 and miR‐33a‐5p‐overexpressing HCT116 were injected into nude mice. In vivo tumour formation was significantly suppressed by miR‐33a‐5p overexpression (P < 0.05) as well as the proliferation marker Ki67 (P < 0.05). Additionally, MTHFD2 protein expression was significantly enhanced in CRC tissues. From bioinformatics predictions and a luciferase report analysis, MTHFD2 was confirmed to be one of the target genes of miR‐33a‐5p. In contrast to the role of miR‐33a‐5p overexpression, MTHFD2 overexpression promoted the proliferation and migration of HCT116 and HT29 cells (P < 0.05), which confirmed that MTHFD2 was a functional target gene of miR‐33a‐5p. In conclusion, miR‐33a‐5p inhibits the growth and migration of CRC by targeting MTHFD2. [ABSTRACT FROM AUTHOR]

S higella sonnei is a bacterial pathogen and causative agent of bacillary dysentery. It deploys a type III secretion system to inject effector proteins into host epithelial cells and macrophages, an essential step for tissue invasion and immune evasion. Although the arsenal of bacterial effectors and their cellular targets have been studied extensively, little is known about the prerequisites for deployment of type III secreted proteins during infection. Here, we describe a novel S . sonnei adhesin, SSO1327 which is a multivalent adhesion molecule ( MAM) required for invasion of epithelial cells and macrophages and for infection in vivo. The S . sonnei MAM mediates intimate attachment to host cells, which is required for efficient translocation of type III effectors into host cells. SSO1327 is non-redundant to IcsA; its activity is independent of type III secretion. In contrast to the up-regulation of IcsA-dependent and independent attachment and invasion by deoxycholate in S higella flexneri, deoxycholate negatively regulates IcsA and MAM in S . sonnei resulting in reduction in attachment and invasion and virulence attenuation in vivo. A strain deficient for SSO1327 is avirulent in vivo, but still elicits a host immune response. [ABSTRACT FROM AUTHOR]

A number of reports have identified HPV DNA in breast cancer specimens and HPV type 16, 18, 31, 33, 45, and 51 were more prevalent. HPV 58 was frequently detected in cervical cancer in Shaanxi China. The aim of the present study was to investigate whether HPV 58 present in breast cancer. 169 cases of breast cancer samples and 83 benign breast lesions were analyzed. Type specific primers and oligonucliotide probe were used for the detection of HPV 58 by conventional PCR and in situ hybridization techniques. The HPV 58 viral load were measured by qPCR. p16 protein expression were evaluated by immunohistochemistry. HPV 58 E7 DNA was detected in 25 out of 169 formalin fixed paraffin embedded breast cancer tissues (14.79%) by PCR, only 1 out of 83 non-malignant breast lesions showed positive (1.20%). The results of ISH showed that 17 out of 169 (10.06%) malignant samples were positive for HPV 58 E7, and only 1 out of 83 non-malignant lesions was positive. Positive p16 immunostaining was observed in all the HPV 58 E7 ISH positive cases, but 16 out of 98 cases with HPV negative were p16 positive. The presence of HPV 58 in both normal duct epithelial cells and carcinoma in situ along with its presence in the cancer cells of the same specimen indicated the possible causal role of HPV 58 in breast cancer. The findings provide a solid morphological evidence of the involvement of HPV 58 in breast cancer development. J. Med. Virol. 87:1034-1040, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT This study prepared TPDA, a high-intrinsic-viscosity cationic polyacrylamide, through ultraviolet (UV)-initiated template polymerization. Acrylamide (AM) and diallyldimethylammonium chloride (DMD) served as monomers, and poly sodium polyacrylate (PAAS) served as the template. The structure of TPDA was characterized by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. The synthetic conditions of TPDA were studied and optimized by single-factor experiments. An optimized product was obtained at an intrinsic viscosity of 11.3 dL g−1 and a conversion rate of 97.2% with a total monomer concentration of 20%, DMD concentration of 30%, initiator concentration of 0.045%, pH of 8, EDTA concentration of 0.3%, and UV irradiation of 90 min. Results showed that TPDA was the copolymer of AM and DMD with a micro-block structure at the molecular chain. Given its high intrinsic viscosity and cationic block structure, TPDA performed better in kaolin flocculation than that prepared without template addition. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41747. [ABSTRACT FROM AUTHOR]

In this study, a new composite flocculant was prepared by premixing polymeric aluminum ferric sulfate (PAFS) with cationic polyacrylamide (CPAM) to treat textile dye wastewater. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were conducted to investigate the structure and morphology of the PAFS-CPAM. The effects of flocculant dosage, initial pH of textile dye wastewater, and settling time after flocculation on the removal of turbidity and chemical oxygen demand (COD) were examined. The flocculation efficiency of PAFS-CPAM for dye treatment was compared with PAFS, CPAM, PAFS/CPAM (PAFS followed by CPAM), and CPAM/PAFS (CPAM followed by PAFS). The synergy of PAFS and CPAM increased the (Fe-Al)b species of PAFS-CPAM. Treatment with PAFS-CPAM was more effective in removing turbidity and COD than PAFS, CPAM, PAFS/CPAM, and CPAM/PAFS. The turbidity and COD removal rates of textile wastewater were higher than 80 and 90% in the pH range of 5.5 to 8.5, respectively. Furthermore, PAFS-CPAM demonstrated excellent performance in reducing sludge volume after flocculation. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40062. [ABSTRACT FROM AUTHOR]

Herpes zoster (HZ) is a Varicella zoster virus infection disease. Previous studies have presumed the connection between development of HZ and involvement of cellular immunity in peripheral blood. However, whether cellular immunity plays a role in the local skin lesion has not been addressed. To explore the levels of T-helper cell (Th)1/Th2 type cytokine profiles in the blister fluid of the skin lesions from the patients with HZ and its role in pathogenesis, we used the cytometric bead array kit to compare the levels of cytokines (interleukin [IL]-2, tumor necrosis factor [TNF]-α, IL-10 and IL-4) in blister fluid from 46 patients with those from the suction blister fluids from 20 volunteers without any infectious disease (the control group). The results indicated that the levels of Th1 cytokines, IL-2 and TNF-α in the blister fluid from the patients' skin lesions were significantly lower than those from the control group, whereas the levels of Th2 cytokines IL-10 and IL-4 were significantly higher than those in the control group. Moreover, significant variation of the levels of Th1/Th2 cytokines (IL-2, TNF-α, IL-10 and IL-4) in the blister fluid from the HZ patients' lesions was also observed among different stages of the disease. It is concluded that a cytokine imbalance was present in the local lesions of patients with HZ during disease development. Our data suggested that the Th immunity was associated with disease activity, which may play an important role in the pathogenesis of HZ. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (BaP) is a representative compound of polycyclic aromatic hydrocarbons exerting cytotoxicity and genotoxicity in the human liver, lung, stomach and skin. However, the toxic effect of BaP on cervical tissue remains unclear. This study was carried out to investigate the toxic effects of BaP on the cervix of ICR mice. Female mice were treated with BaP by intraperitoneal injection and oral gavage at a dose of 2.5, 5 and 10 mg/kg body-weight, twice a week for 14 weeks. BaP treatment caused a significant increase in the levels of MDA and IL-6 with significantly increased activity of CYP1A1, creatine kinase and aspartate aminotransferase (AST) and decreased activity of glutathione- S-transferase in the cervix and liver. The relative cervix weight was markedly reduced in the intraperitoneal BaP injection groups, whereas only a slight reduction was observed in the oral gavage groups. The increase in weight decreased with increasing BaP dose. Moreover, BaP treatment induced significant pathomorphological changes in the cervical tissue and increased the mortality of the mice. Taken together, these results suggest that BaP causes a certain toxic effect on cervical tissue. [ABSTRACT FROM AUTHOR]

To test whether homeostasis-driven T cell proliferation in reconstituted lymphodepleted hosts would improve the therapeutic efficacy of tumor vaccines, normal mice and reconstituted lymphopenic mice (RLM; C57BL/6 mice rendered lymphopenic with sublethal total-body irradiation and reconstituted with naive splenocytes) were used in the vaccination and challenge experiments with weakly immunogenic F10 melanoma cells. Only limited protection was observed in vaccinated normal mice (16.7%), whereas significantly greater protection was induced in vaccinated RLM (63.2%). Protective immunity in RLM depended on CD8 T cells. Following vaccination, a significant increase in the percentage of CD44 [ABSTRACT FROM AUTHOR]

The X-ray crystallographic structures of two mutants (K206Q and H207E) of the N-lobe of human transferrin (hTF/2N) have been determined to high resolution (1.8 and 2.0 +, respectively). Both mutant proteins bind iron with greater affinity than native hTF/2N. The structures of the K206Q and H207E mutants show interactions (both H-bonding and electrostatic) that stabilize the interaction of Lys296 in the closed conformation, thereby stabilizing the iron bound forms. [ABSTRACT FROM PUBLISHER]

Trap‐assisted non‐radiative recombination losses and moisture‐induced degradation significantly impede the development of highly efficient and stable inverted (p–i–n) perovskite solar cells (PSCs), which require high‐quality perovskite bulk. In this research, we mitigate these challenges by integrating thermally stable perovskite layers with Lewis base covalent organic frameworks (COFs). The ordered pore structure and surface binding groups of COFs facilitate cyclic, multi‐site chelation with undercoordinated lead ions, enhancing the perovskite quality across both its bulk and grain boundaries. This process not only reduces defects but also promotes improved energy alignment through n‐type doping at the surface. The inclusion of COF dopants in p–i–n devices achieves power conversion efficiencies (PCEs) of 25.64 % (certified 24.94 %) for a 0.0748‐cm2 device and 23.49 % for a 1‐cm2 device. Remarkably, these devices retain 81 % of their initial PCE after 978 hours of accelerated aging at 85°C, demonstrating remarkable durability. Additionally, COF‐doped devices demonstrate excellent stability under illumination and in moist conditions, even without encapsulation. [ABSTRACT FROM AUTHOR]

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044., (© 2020 Wiley Periodicals LLC.)