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Summary: Background: Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. Objective/Methods: We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. Results: Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non‐sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA‐IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non‐sedentary subtypes who had similar DBP levels. Conclusion: Children of different lifestyle‐based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity. [ABSTRACT FROM AUTHOR]

As a traditional nonage‐hardenable aluminum alloy, 5XXX aluminum alloy has a limited dispersion‐strengthening effect since it is challenging to obtain high‐density and fine‐sized dispersoids by a conventional homogenization treatment process. In this work, three different homogenization treatments, single‐stage homogenization, slope heating homogenization, and double‐stage homogenization are used in a new type Al–Mg–Mn–Er alloy to exploit the dispersion strengthening. The precipitation behavior of submicron‐sized Mn‐containing dispersoids and nanosized Al3Er precipitates is investigated. In single‐stage homogenization, the nucleation of the Mn‐containing dispersoid is completed within a span of 2 h at 460 °C, accompanied by noticeable coarsening and the Al3Er precipitate tended to nucleate at dislocation sites and form a chain‐like structure. In slope heating and double‐stage homogenization, during the initial phase of heat treatment, lower temperatures facilitate the nucleation of dispersoids. This leads to the uniform precipitation of Mn‐containing dispersoids within the grain interior and improves the chain distribution of the Al3Er precipitates. The double‐stage homogenization generates the finest dispersoids. The alloy reaches maximum strength in the double‐stage homogenization, and the yield strength is 177 MPa, representing a 22% increase compared to the single‐stage homogenization. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptors (TNFRs) are promising targets for cancer therapy. However, activating their downstream signaling requires cross‐linking of TNFRs. Herein, to devise strong agonists of TNFRs, ligands targeting TNFRs, such as OX40L and tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), were fused with a multivalent protein scaffold (MV) to prepare multivalent agonists for cross‐linking TNFRs. The nano‐clustered multivalent‐OX40L (MV‐OX40L) and MV‐TRAIL could promote T cell activation and directly induce tumor cell apoptosis. Moreover, to develop a universal nano‐adaptor for the rapid preparation of multivalent agonists of different TNFRs, the Fc receptor that could immobilize antibodies was fused with MV to prepare MV‐FcR, which could multimerize commercial agonist antibodies targeting TNFRs, such as anti‐OX40 antibody (αOX40). Simply incubating αOX40 with MV‐FcR could prepare MV‐αOX40 to enhance its antitumor efficacy. In addition, MV‐FcR could multimerize with other therapeutic antibodies, such as anti‐PD‐L1 antibody, to enhance their valency. This study provides a promising strategy for engineering multivalent antitumor protein drugs. [ABSTRACT FROM AUTHOR]

The past decades have witnessed the rapid development and widespread application of nanomedicines in cancer treatment; however, the clinical translation of experimental findings has been low, as evidenced by the low percentage of commercialized nanomedicines. Incomplete understanding of nanomedicine‐tumor interactions and inappropriate evaluation models are two important challenges limiting the clinical translation of cancer nanomedicines. Currently, nanomedicine‐tumor interaction and therapeutic effects are mainly investigated using cell lines or mouse models, which do not recapitulate the complex tumor microenvironment in human patients. Thus, information obtained from cell lines and mouse models cannot provide adequate guidance for the rational redesign of nanomedicine. Compared with other preclinical models, tumor organoids constructed from patient‐derived tumor tissues are superior in retaining the key histopathological, genetic, and phenotypic features of the parent tumor. We speculate that organoid technology would help elucidate nanomedicine‐tumor interaction in the tumor microenvironment and guide the design of nanomedicine, making it a reliable tool to accurately predict drug responses in patients with cancer. This review highlighted the advantages of drug delivery systems in cancer treatment, challenges limiting the clinical translation of antitumor nanomedicines, and potential application of patient‐derived organoids (PDO) in nanomedicine. We propose that combining organoids and nanotechnology would facilitate the development of safe and effective cancer nanomedicines and accelerate their clinical application. This review discussed the potential translational value of integrative research using organoids and cancer nanomedicine. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease [ABSTRACT FROM AUTHOR]

The overexpressed glutathione peroxidase4 (GPX4) and insufficient H2O2 in tumor cells weaken ferroptosis therapy and the elicited anticancer immune response. Herein, a rigid metal‐polyphenol shell decorated nanodevice ssPPELap@Fe‐TA is constructed to successfully overcome the drawbacks of ferroptosis therapy. The ssPPELap@Fe‐TA consists of a rigid Fe‐TA network‐based shell and disulfide‐containing polyphosphoester (ssPPE) core with β‐lapachone loading. The rigid Fe‐TA network‐based shell of ssPPELap@Fe‐TA enables its efficient internalization by tumor cell and then disintegrates in the acidic endosome/lysosome to initiate Fe3+/Fe2+ conversion‐driven ferroptosis. The ssPPE core will deplete glutathione (GSH) via the disulfide‐thiol exchange reaction to inactivate GPX4, and also trigger the release of β‐lapachone to significantly increase intracellular H2O2 and then promote Fe3+‐mediated Fenton reaction, eventually achieving strong inhibition of tumor progression. Moreover, ssPPELap@Fe‐TA elicites a robust systemic antitumor immune response by promoting dendritic cells (DCs) maturation and T cell infiltration, and synergizes with anti‐PD‐L1 antibody (a‐PD‐L1) to strikingly suppress 4T1 tumor growth and lung metastasis. [ABSTRACT FROM AUTHOR]

Background or Purpose: A practical noninvasive method to identify sentinel lymph node (SLN) status in breast cancer patients, who had a suspicious axillary lymph node (ALN) at ultrasound (US), but a negative clinical physical examination is needed. To predict SLN metastasis using a nomogram based on US and biopsy‐based pathological features, this retrospective study investigated associations between clinicopathological features and SLN status. Methods: Patients treated with SLN dissection at four centers were apportioned to training, internal, or external validation sets (n = 472, 175, and 81). Lymph node ultrasound and pathological characteristics were compared using chi‐squared and t‐tests. A nomogram predicting SLN metastasis was constructed using multivariate logistic regression models. Results: In the training set, statistically significant factors associated with SLN+ were as follows: histology type (p < 0.001); progesterone receptor (PR: p = 0.003); Her‐2 status (p = 0.049); and ALN‐US shape (p = 0.034), corticomedullary demarcation (CMD: p < 0.001), and blood flow (p = 0.001). With multivariate analysis, five independent variables (histological type, PR status, ALN‐US shape, CMD, and blood flow) were integrated into the nomogram (C‐statistic 0.714 [95% CI: 0.688–0.740]) and validated internally (0.816 [95% CI: 0.784–0.849]) and externally (0.942 [95% CI: 0.918–0.966]), with good predictive accuracy and clinical applicability. Conclusion: This nomogram could be a direct and reliable tool for individual preoperative evaluation of SLN status, and therefore aids decisions concerning ALN dissection and adjuvant treatment. [ABSTRACT FROM AUTHOR]

The passive diffusion performance of nanocarriers results in inefficient drug transport across multiple biological barriers and consequently cancer therapy failure. Here, a magnetically driven amoeba-like nanorobot (amNR) is presented for whole-process active drug transport. The amNR is actively extravasated from blood vessels and penetrated into deep tumor tissue through a magnetically driven deformation effect. Moreover, the acidic microenvironment of deep tumor tissue uncovers the masked targeting ligand of amNR to achieve active tumor cell uptake. Furthermore, the amNR rapidly releases the encapsulated doxorubicin (DOX) after alternating magnetic field application. The amNRs eventually deliver DOX into ≈92.3% of tumor cells and completely delay tumor growth with an inhibition rate of 96.1%. The deformable amNRs, with the assistance of magnetic field application, provide a facile strategy for whole-process active drug transport. [ABSTRACT FROM AUTHOR]

Recently, the increasing significance of the epicardium in cardiac development and regeneration is beginning to be recognized. However, because of the small proportion of primary epicardial cells and the limited cell culture time, further research on the mechanism of epicardial cells is hindered. Here, we transfected simian virus 40 Large T (SV40-LT) into primary epicardial cells to establish an immortalized cell line, named EpiSV40. We further demonstrated that EpiSV40 can be easy to culture and has the proliferation, migration and differentiation capacities comparable to primary epicardial cells. EpiSV40 can serve as an ideal in vitro model for epicardial cell research, which will booster the study of the epicardium in cardiac development and heart regeneration. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of improved perioperative sleep on pain, analgesic consumption, and postoperative nausea and vomiting (PONV) in patients who were undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA). Methods: Original studies published from 1 January 1970 to 30 September 2020 were queried in three unique databases using a common search term. The searches sought randomized controlled trials (RCT) investigating the effectiveness of sleep quality or quantity interventions for pain control early after TKA or THA. Grey literature was also searched by screening trial registers. There was no limitation on published language and patients. Two reviewers then assessed studies for eligibility. Eligible studies should have primary outcomes including perioperativeWe have comfirmed the edits. visual analogue scale (VAS) pain score and analgesic consumption; and secondary outcomes including side effects, such as PONV. Data extracted from the literature were abstracted into a comma‐separated database spreadsheet using Microsoft Excel. A meta‐analysis was then performed. Pooled statistics were calculated with weighting by inverse variance assuming a random effect model. I2 was calculated as a quantifier of heterogeneity and interpreted according to the Cochrane manual. All data analysis was performed using Revman software. Results: From a total of 1285 potential records identified in the electronic search, six studies eventually fulfilled the eligibility criteria. The six controlled RCTs consisted of 207 patients in the sleep‐improving group and 209 patients in the control group. The severity of rest pain was significantly lower in the sleep‐improving group compared with the control group at day 1 and day 3 postoperatively; the severity of active pain was significantly lower in the sleep‐improving group compared with the control group at day 3 postoperatively. Data concerning analgesic drugs could not undergo a meta‐analysis due to the difference of eligible studies. No significant difference was found in the incidence of PONV between the sleep‐improving group and the control group. Conclusion: Improved perioperative sleep, regardless of quality or quantity, could significantly reduce the pain level at the early stage after TKA or THA, thus the total amount of analgesic drugs consumed was decreased, without significant increase in the incidence of PONV. [ABSTRACT FROM AUTHOR]

Objectives: Articular cartilage plays a vital role in bearing and buffering. Injured cartilage and subchondral bone repair is a crucial challenge in cartilage tissue engineering due to the peculiar structure of osteochondral unit and the requirement of osteogenic/chondrogenic bi‐directional differentiation. Based on the bionics principle, a nanotextured silk fibroin (SF)‐chondroitin sulphate (CS)/hydroxyapatite (HAp) nanowire tough bilayer structure was prepared for osteochondral repair. Methods: The SF‐CS/HAp membrane was constructed by alcohol‐induced β‐sheet formation serving as the physical crosslink. Its osteochondral repairing capacity was evaluated by culturing bone marrow mesenchymal stem cells (BMSCs) in vitro and constructing a rat osteochondral defect model in vivo. Results: The bilayer SF‐CS/HAp membrane with satisfactory mechanical properties similar to natural cartilage imitated the natural osteochondral unit structural layers and exerted the function of bearing and buffering timely after in vivo implantation. SF‐CS layer upregulated the expression of chondrogenesis‐related genes of BMSCs by surface nanotopography and sustained release CS. Meanwhile, nanotextured HAp layer assembled with nanowire endowed the membrane with an osteogenic differentiation tendency for BMSCs. In vivo results proved that the biomimetic bilayer structure dramatically promoted new cartilage formation and subchondral bone remodelling for osteochondral defect model after implantation. Conclusions: The SF‐CS/HAp biomimetic bilayer membrane provides a promising strategy for precise osteochondral repair. [ABSTRACT FROM AUTHOR]

Background: The incidence of bilateral breast cancer (BBC) is increasing nowadays comprising 2%‐11% of all breast cancer (BC). According to the interval time between the first and second cancer, BBC could be divided into synchronous (SBBC) and metachronous (MBBC). However, this interval time is quite different across studies. It remains controversial whether the survival of BBC, SBBC, and MBBC is similar or worse compared to that of unilateral breast cancer (UBC), and whether the survival of SBBC is similar or worse compared to MBBC. To better understand the survival of UBC, BBC, SBBC, and MBBC and how the interval time would influence the prognosis of SBBC and MBBC, we performed this meta‐analysis on studies from recent 10 years (2008‐2018). Methods: Databases of PubMed, Embase, and Web of Science were searched for relevant studies within recent 10 years. Hazard ratio (HR) was adopted to evaluate the difference of overall survival (OS) of UBC, BBC, SBBC, and MBBC. HR of OS comparisons were performed between BBC vs UBC, SBBC vs UBC, MBBC vs UBC, and SBBC vs MBBC with 3, 6, 12 months as the interval time, respectively. Results: There were 15 studies of 72 302 UBC and 2912 BBC included in the meta‐analysis. The summary HR of OS comparison between BBC vs UBC was 1.68 (95% CI: 1.28‐2.20), SBBC vs UBC was 2.01 (95% CI: 1.14‐3.55), MBBC vs UBC was 3.22 (95% CI: 0.75‐13.78). When 3, 6, 12 months were used as the interval time, the summary HR of the OS comparison between of SBBC vs MBBC were 0.64 (95% CI: 0.44‐0.94), 1.17 (95% CI: 0.84‐1.63) and 1.45 (95% CI: 1.10‐1.92), respectively. Conclusion: BBC and SBBC showed worse prognosis in terms of OS compared to UBC while MBBC manifested similar or non‐superior survival as UBC. The OS comparison between SBBC and MBBC changed with different interval time used. The longer the interval time used, the worse the survival of SBBC. SBBC with interval of 3‐12 months between the two cancers had the worst prognosis. When 6 months was used to differentiate SBBC from MBBC, these two clinical entities showed similar OS. [ABSTRACT FROM AUTHOR]

Abstract: Nanocarriers with intelligent transactivator of transcription (TAT) targeting properties are of particular interest for on‐demand drug delivery in the field of precision nanomedicine. Nevertheless, the key challenge of this strategy is the slowness of activating TAT peptide at the targeted tissue. As a proof‐of‐concept, polymeric micelles STAT‐NPIR&DOX with photoswitchable ultrafast TAT targeting effect are designed and explored. The hydrophilic shell of STAT‐NPIR&DOX consists of a TAT‐functionalized short‐chain poly(ethylene glycol) and a thermoresponsive long‐chain polyphosphoester (PPE). In nontumor tissue, the TAT peptide of STAT‐NPIR&DOX is masked by long‐chain PPE to minimize nonspecific uptake of nanocarriers. Upon near‐infrared (NIR) photoactivation, the TAT peptide is ultrafastly reexposed (within 60 s) via the collapse of thermoresponsive PPE, resulting in significantly enhanced cellular uptake of nanocarrier by tumor cells. Such photoswitchable TAT targeting effect efficiently avoids nonspecific uptake by nontumor cells and enhances tumor cell uptake, achieving tumor‐specific on‐demand drug delivery and superior anticancer efficacy. This approach using NIR light‐induced TAT targeting effect can be extended to a variety of applications for on‐demand drug delivery, which also provides new avenues for phototargeted drug delivery. [ABSTRACT FROM AUTHOR]

Background Tea, a common beverage, has been suggested to exhibit a number of health benefits. However, one of its active ingredients, caffeine, has been associated with preterm birth and low birthweight. We investigated whether tea consumption during early pregnancy is associated with an increased risk of preterm birth and abnormal fetal growth. Methods A total of 8775 pregnant women were included from the Born in Guangzhou Cohort Study. Tea consumption (type, frequency, and strength) during their first trimester and social and demographic factors were obtained by way of questionnaires administered during pregnancy. Information on birth outcomes and complications during pregnancy was obtained from hospital medical records. Results Overall habitual tea drinking (≥1 serving/week) prevalence among pregnant women was low, at 16%. After adjustment for potential confounding factors (eg, maternal age, educational level, monthly income) tea drinking during early pregnancy was not associated with an increased risk of preterm birth or abnormal fetal growth (small or large for gestational age) ( P>.05). Conclusions We did not identify a consistent association between frequency of tea consumption or tea strength and adverse birth outcomes among Chinese pregnant women with low tea consumption. Our findings suggest that occasional tea drinking during pregnancy is not associated with increased risk of preterm birth or abnormal fetal growth. Given the high overall number of annual births in China, our findings have important public health significance. [ABSTRACT FROM AUTHOR]

Low-density lipoproteins (LDLs) are a class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. A facile procedure is used for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts. According to a hypothesized mechanism, the reconstituted LDLs can also enable metabolism-triggered drug release while preventing the payloads from lysosomal degradation. This study demonstrates that LDLs reconstructed with fatty acids hold great promise to serve as effective and versatile nanocarriers for targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Anticancer modalities based on oxygen free radicals, including photodynamic therapy and radiotherapy, have emerged as promising treatments in the clinic. However, the hypoxic environment in tumor tissue prevents the formation of oxygen free radicals. Here we introduce a novel strategy that employs oxygen-independent free radicals generated from a polymerization initiator for eradicating cancer cells. The initiator is mixed with a phase-change material and loaded into the cavities of gold nanocages. Upon irradiation by a near-infrared laser, the phase-change material is melted due to the photothermal effect of gold nanocages, leading to the release and decomposition of the loaded initiator to generate free radicals. The free radicals produced in this way are highly effective in inducing apoptosis in hypoxic cancer cells. [ABSTRACT FROM AUTHOR]

Long noncoding RNA SPRY4‐IT1 has been reported to promote melanoma cell growth and invasion, and to block apoptosis. The purpose of this study was to investigate the clinical significance of SPRY4‐IT1 in patients with malignant melanoma. The relative expression levels of SPRY4‐IT1 were measured in plasma samples from 70 patients and 79 healthy controls by quantitative reverse transcriptase polymerase chain reaction. SPRY4‐IT1 expression is high in melanoma patients but low in healthy controls, and is closely associated with tumor site and tumor stage. Elevated SPRY4‐IT1 significantly reduces overall survival rates of patients and is considered as an independent prognostic factor in patients with melanoma. The prognostic nomogram shows a good prediction of the probability of 5‐year overall survival of patients with melanoma (c‐index: 0.72). The calibration curve for the probability of survival presents good agreement between actual outcomes and predictive consequences. In summary, SPRY4‐IT1 may be a potential prognostic marker and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Ein Hybridnanosystem …… für die sauerstoffunabhängige Erzeugung freier Radikale zur Abtötung von Krebszellen unter hypoxischen Bedingungen stellen Y. Xia et al. in ihrer Zuschrift auf S. 8927 ff. vor. Mit einem Phasenwechselmaterial befüllte Gold‐Nanokäfige werden zum Transport eines Polymerisationsinitiators genutzt, der bei Bestrahlung mit einem Nahinfrarotlaser die Radikale erzeugt. [ABSTRACT FROM AUTHOR]

Background: Tea, a common beverage, has been suggested to exhibit a number of health benefits. However, one of its active ingredients, caffeine, has been associated with preterm birth and low birthweight. We investigated whether tea consumption during early pregnancy is associated with an increased risk of preterm birth and abnormal fetal growth., Methods: A total of 8775 pregnant women were included from the Born in Guangzhou Cohort Study. Tea consumption (type, frequency, and strength) during their first trimester and social and demographic factors were obtained by way of questionnaires administered during pregnancy. Information on birth outcomes and complications during pregnancy was obtained from hospital medical records., Results: Overall habitual tea drinking (≥1 serving/week) prevalence among pregnant women was low, at 16%. After adjustment for potential confounding factors (eg, maternal age, educational level, monthly income) tea drinking during early pregnancy was not associated with an increased risk of preterm birth or abnormal fetal growth (small or large for gestational age) (P>.05)., Conclusions: We did not identify a consistent association between frequency of tea consumption or tea strength and adverse birth outcomes among Chinese pregnant women with low tea consumption. Our findings suggest that occasional tea drinking during pregnancy is not associated with increased risk of preterm birth or abnormal fetal growth. Given the high overall number of annual births in China, our findings have important public health significance., (© 2017 Wiley Periodicals, Inc.)