In this paper, a simple, but effective method is reported to construct the core−shell gold nanorod@metal–organic frameworks (AuNR@MOFs) as a multifunctional theranostic platform by using ...functionalized AuNRs as seed crystal for the growth of porphyrinic MOFs on the surface of AuNR. Such a delicate tunable core−shell composite not only possesses the improved drug loading efficiency, near‐infrared light‐trigger drug release, and fluorescence imaging, but also can produce reactive oxygen species as well as photothermal activity to achieve combined cancer therapy. It is further demonstrated that the camptothecin loaded AuNR@MOFs show distinctively synergistic efficiency for damaging the cancer cell in vitro and inhibiting the tumor growth and metastasis in vivo. The development of this high‐performance incorporated nanostructure will provide more perspectives in the design of versatile nanomaterials for biomedical applications.
Porphyrinic metal–organic frameworks coated gold nanorods (AuNR@MOFs) are reported as a theranostic platform for combined photodynamic/photothermal/chemotherapy of tumor. The delicate core–shell AuNR@MOFs not only possess improved drug loading efficiency, near‐infrared light‐triggered drug release, and fluorescence imaging, but also are able to produce reactive oxygen species as well as photothermal activity to achieve synergistic tumor therapy.
Many COVID-19 patients infected by SARS-CoV-2 virus develop pneumonia (called novel coronavirus pneumonia, NCP) and rapidly progress to respiratory failure. However, rapid diagnosis and ...identification of high-risk patients for early intervention are challenging. Using a large computed tomography (CT) database from 3,777 patients, we developed an AI system that can diagnose NCP and differentiate it from other common pneumonia and normal controls. The AI system can assist radiologists and physicians in performing a quick diagnosis especially when the health system is overloaded. Significantly, our AI system identified important clinical markers that correlated with the NCP lesion properties. Together with the clinical data, our AI system was able to provide accurate clinical prognosis that can aid clinicians to consider appropriate early clinical management and allocate resources appropriately. We have made this AI system available globally to assist the clinicians to combat COVID-19.
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•AI system that can diagnose COVID-19 pneumonia using CT scans•Prediction of progression to critical illness•Potential to improve performance of junior radiologists to the senior level•Can assist evaluation of drug treatment effects with CT quantification
Zhang et al. present an AI-based system, based on hundreds of thousands of human lung CT scan images, that can aid in distinguishing patients NCP versus other common pneumonia and can help to predict the prognosis of COVID-19 patients.
Abstract
Sclerostin negatively regulates bone formation by antagonizing Wnt signalling. An antibody targeting sclerostin for the treatment of postmenopausal osteoporosis was approved by the U.S. Food ...and Drug Administration, with a boxed warning for cardiovascular risk. Here we demonstrate that sclerostin participates in protecting cardiovascular system and inhibiting bone formation via different loops. Loop3 deficiency by genetic truncation could maintain sclerostin’s protective effect on the cardiovascular system while attenuating its inhibitory effect on bone formation. We identify an aptamer, named aptscl56, which specifically targets sclerostin loop3 and use a modified aptscl56 version, called Apc001PE, as specific in vivo pharmacologic tool to validate the above effect of loop3. Apc001PE has no effect on aortic aneurysm and atherosclerotic development in
ApoE
−/−
mice and
hSOST
ki
.ApoE
−/−
mice with angiotensin II infusion. Apc001PE can promote bone formation in
hSOST
ki
mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation.
Telluride molybdenum (MoTe2) nanosheets with wide near‐infrared (NIR) absorbance are functionalized with polyethylene glycol‐cyclic arginine‐glycine‐aspartic acid tripeptide (PEG‐cRGD). After loading ...a chemotherapeutic drug (doxorubicin, DOX), MoTe2‐PEG‐cRGD/DOX is used for combined photothermal therapy and chemotherapy. With the high photothermal conversion efficiency, MoTe2‐PEG‐cRGD/DOX exhibits favorable cells killing ability under NIR irradiation. Owing to the cRGD‐mediated specific tumor targeting, MoTe2‐PEG‐cRGD/DOX shows efficient accumulation in tumors to induce a strong tumor ablation effect. MoTe2‐PEG‐cRGD nanosheets, which are relatively stable in the circulation, could be degraded under NIR ray. The in vitro and in vivo experimental results demonstrate that this theranostic nanoagent, which could accumulate in tumors to allow photothermal imaging and combined therapy, is readily degradable in normal organs to enable rapid excretion and avoid long‐term retention/toxicity, holding great potential to treat tumor effectively.
A degradable photothermal agent‐mediated, drug‐loaded nanocarrier is developed for photothermal imaging and chemical/photothermal combined therapy. The in vitro and in vivo experimental results demonstrate that this theranostic nanoagent can accumulate in tumors to allow photothermal imaging and combined therapy, and be readily degradable in normal organs to enable rapid excretion and avoid long‐term retention/toxicity.
Despite considerable advances devoted to improving the operational stability of organic solar cells (OSCs), the metastable morphology degradation remains a challenging obstacle for their practical ...application. Herein, the stabilizing function of the alloy states in the photoactive layer from the perspective of controlling the aggregation characteristics of non‐fullerene acceptors (NFAs), is revealed. The alloy‐like model is adopted separately into host donor and acceptor materials of the state‐of‐the‐art binary PM6:BTP‐4Cl blend with the self‐stable polymer acceptor PDI‐2T and small molecule donor DRCN5T as the third components, delivering the simultaneously enhanced photovoltaic efficiency and storage stability. In such ternary systems, two separate arguments can rationalize their operating principles: (1) the acceptor alloys strengthen the conformational rigidity of BTP‐4Cl molecules to restrain the intramolecular vibrations for rapid relaxation of high‐energy excited states to stabilize BTP‐4Cl acceptor. (2) The donor alloys optimize the fibril network microstructure of PM6 polymer to restrict the kinetic diffusion and aggregation of BTP‐4Cl molecules. According to the superior morphological stability, non‐radiative defect trapping coefficients can be drastically reduced without forming the long‐lived, trapped charge species in ternary blends. The results highlight the novel protective mechanisms of engineering the alloy‐like composites for reinforcing the long‐term stability of NFA‐based ternary OSCs.
The stabilizing function of the alloy states is revealed based on simultaneous efficiency and storage stability boosting in PM6:BTP‐4Cl:PDI‐2T and PM6:DRCN5T:BTP‐4Cl ternary devices. The improved stability can be rationalized by two mechanisms: (1) the acceptor alloys enhance the conformational rigidity of BTP‐4Cl molecules. (2) The donor alloys optimize the fibril network of PM6 to restrict the aggregation of the BTP‐4Cl acceptor.
Elderly cancer patients are at particularly high risk for malnutrition because both the disease and the old age threaten their nutritional status. The Global Leadership Initiative on Malnutrition ...(GLIM) released new universal criteria for diagnosing and grading malnutrition, but the validation of these criteria in elderly cancer population is not well documented. Our objective was to investigate the application of the GLIM criteria in nutrition assessment and survival prediction in elderly cancer patients.
This retrospective cohort analysis was conducted on a primary cohort of 1192 cancer patients aged 65 years or older enrolled from a multi-institutional registry, and a validation cohort of 300 elderly cancer patients treated at the First Affiliated Hospital of Sun Yat-sen University. Patients considered at-risk for malnutrition based on the NRS-2002 were assessed using the GLIM criteria. The association between the nutritional status and patients' overall survival (OS) was then analyzed by the Kaplan–Meier method and a Cox model. A nomogram was also established that included additional independent clinical prognostic variables. To determine the predictive accuracy and discriminatory capacity of the nomogram, the C-index, receiver operating characteristic (ROC) curve and calibration curve were evaluated.
The percentage of patients considered “at-risk” for malnutrition was 64.8% and 67.3% for the primary and validation cohorts, respectively. GLIM-defined malnutrition was diagnosed in 48.4% of patients in the primary cohort and 46.0% in the validation cohort. In the primary cohort, patients at risk of malnutrition (NRS-2002 ≥ 3) showed a worse OS than those with a NRS-2002 < 3 (HR 1.34, 1.10–1.64; p = 0.003). Additionally, patients with GLIM-defined severe malnutrition (HR1.71, 1.37–2.14; p < 0.001) or moderate malnutrition (HR1.35, 1.09–1.66; p = 0.006) showed a significantly shorter OS compared to those without malnutrition. The nomogram incorporating the domains of the GLIM with other variables was accurate, especially for predicting the 1- and 2-year overall survival rates.
The GLIM criteria can be used in elderly cancer patients not only to assess malnutrition, but also to predict survival outcome. The nomogram developed based on the GLIM domains can provide a more accurate prediction of the prognosis than existing systems.
Aptamers are promising therapeutic and diagnostic agents for various diseases due to their high affinity and specificity against target proteins. Structural determination in combination with multiple ...biochemical and biophysical methods could help to explore the interacting mechanism between aptamers and their targets. Regrettably, structural studies for aptamer-target interactions are still the bottleneck in this field, which are facing various difficulties. In this review, we first reviewed the methods for resolving structures of aptamer-protein complexes and for analyzing the interactions between aptamers and target proteins. We summarized the general features of the interacting nucleotides and residues involved in the interactions between aptamers and proteins. Challenges and perspectives in current methodologies were discussed. Approaches for determining the binding affinity between aptamers and target proteins as well as modification strategies for stabilizing the binding affinity of aptamers to target proteins were also reviewed. The review could help to understand how aptamers interact with their targets and how alterations such as chemical modifications in the structures affect the affinity and function of aptamers, which could facilitate the optimization and translation of aptamers-based theranostics.
In this paper, the finite-time control problem of a class of nonlinear underactuated systems is addressed. By using the auxiliary state generated by a time-varying oscillator-like differential ...equation and constructing a novel Lyapunov-like function, a time-varying dynamic feedback controller is designed for such nonlinear underactuated systems. It is proved that the state of the closed-loop system converges to zero at the finite time and the controls are bounded. As an application, the finite-time tracking problem for underactuated axisymmetric systems is solved. Numerical simulations verify the effectiveness of the proposed methods.
It is highly desirable to reduce the membrane thickness in order to maximize the throughput and break the trade-off limitation for membrane-based gas separation. Two-dimensional membranes composed of ...atomic-thick graphene or graphene oxide nanosheets have gas transport pathways that are at least three orders of magnitude higher than the membrane thickness, leading to reduced gas permeation flux and impaired separation throughput. Here we present nm-thick molecular sieving membranes composed of porous two-dimensional metal-organic nanosheets. These membranes possess pore openings parallel to gas concentration gradient allowing high gas permeation flux and high selectivity, which are proven by both experiment and molecular dynamics simulation. Furthermore, the gas transport pathways of these membranes exhibit a reversed thermo-switchable feature, which is attributed to the molecular flexibility of the building metal-organic nanosheets.
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