This article argues that advanced democracies face a dual crisis of rising inequality and population aging, which jointly put pressure on welfare regime sustainability. Particularly vulnerable are ...young people and the elderly in the context of these structural changes. As a result, young people and senior citizens in advanced democracies are increasingly focused on economic equality, which in turn undermines their support for democracy in its current form that prioritizes liberal economic policies. Survey data collected between 2010 and 2020 support the argument. Regardless of the political issues on which they differ, young and old appear to share similar views on what constitutes an ideal democracy.
Triplet-triplet annihilation upconversion nanoparticles have attracted considerable interest due to their promises in organic chemistry, solar energy harvesting and several biological applications. ...However, triplet-triplet annihilation upconversion in aqueous solutions is challenging due to sensitivity to oxygen, hindering its biological applications under ambient atmosphere. Herein, we report a simple enzymatic strategy to overcome oxygen-induced triplet-triplet annihilation upconversion quenching. This strategy stems from a glucose oxidase catalyzed glucose oxidation reaction, which enables rapid oxygen depletion to turn on upconversion in the aqueous solution. Furthermore, self-standing upconversion biological sensors of such nanoparticles are developed to detect glucose and measure the activity of enzymes related to glucose metabolism in a highly specific, sensitive and background-free manner. This study not only overcomes the key roadblock for applications of triplet-triplet annihilation upconversion nanoparticles in aqueous solutions, it also establishes the proof-of-concept to develop triplet-triplet annihilation upconversion nanoparticles as background free self-standing biological sensors.
Prognosis of patients with colorectal cancer (CRC) is generally poor because of the lack of simple, convenient, and noninvasive tools for CRC detection at the early stage. The discovery of microRNAs ...(miRNAs) and their different expression profiles among different kinds of diseases has opened a new avenue for tumor diagnosis. We built a serum microRNA expression profile signature and tested its specificity and sensitivity as a biomarker in the diagnosis of CRC. We also studied its possible role in monitoring the progression of CRC. We conducted a two phase case-control test to identify serum miRNAs as biomarkers for CRC diagnosis. Using quantitative reverse transcription polymerase chain reactions, we tested ten candidate miRNAs in a training set (30 CRCs vs 30 controls). Risk score analysis was used to evaluate the diagnostic value of the serum miRNA profiling system. Other independent samples, including 83 CRCs and 59 controls, were used to validate the diagnostic model. In the training set, six serum miRNAs (miR-21, let-7g, miR-31, miR-92a, miR-181b, and miR-203) had significantly different expression levels between the CRCs and healthy controls. Risk score analysis demonstrated that the six-miRNA-based biomarker signature had high sensitivity and specificity for distinguishing the CRC samples from cancer-free controls. The areas under the receiver operating characteristic (ROC) curve of the six-miRNA signature profiles were 0.900 and 0.923 for the two sets of serum samples, respectively. However, for the same serum samples, the areas under the ROC curve used by the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were only 0.649 and 0.598, respectively. The expression levels of the six serum miRNAs were also correlated with CRC progression. Thus, the identified six-miRNA signature can be used as a noninvasive biomarker for the diagnosis of CRC, with relatively high sensitivity and specificity.
Organic triplet–triplet annihilation upconversion (TTA-UC) materials have considerable promise in areas as broad as biology, solar energy harvesting, and photocatalysis. However, the development of ...highly efficient near-infrared (NIR) light activatable TTA-UC systems remains extremely challenging. In this work, we report on a method of systematically tailoring an annihilator to attain such outstanding systems. By chemical modifications of a commonly used perylene annihilator, we constructed a family of perylene derivatives that have simultaneously tailored triplet excited state energy (T1) and singlet excited state energy (S1), two key annihilator factors to determine TTA-UC performance. Via this method, we were able to tune the TTA-UC system from an endothermic type to an exothermic one, thus significantly elevating the upconversion performance of NIR light activatable TTA upconversion systems. In conjunction with the photosensitizer PdTNP (10 μM), the upconversion efficiency using the optimal annihilator (100 μM) identified in this study was measured to be 14.1% under the low-power density of NIR light (100 mW/cm2, 720 nm). Furthermore, using such a low concentration of perylene derivative, we demonstrated that the optimal TTA-UC pair developed in our study can act as a highly effective light wavelength up-shifter to enable NIR light to drive a photoredox catalysis that otherwise requires visible light. We found that such an NIR driven method is highly effective and can even surpass directly visible light driven photoredox catalysis. This method is important for photoredox catalysis as NIR light can penetrate much deeper in colored photoredox catalysis reaction solutions, especially when done in a large-scale manner. Furthermore, this TTA-UC mediated photoredox catalysis reaction is found to be outdoor sunlight operable. Thus, our study provides a solution to enhance NIR activatable organic upconversion and set the stage for a wide array of applications that have previously been limited by the suboptimal efficiency of the existing TTA upconversion materials.
Although Fenton or Fenton‐like reactions have been widely used in the environment, biology, life science, and other fields, the sharp decrease in their activity under macroneutral conditions is still ...a large problem. This study reports a MoS2 cocatalytic heterogeneous Fenton (CoFe2O4/MoS2) system capable of sustainably degrading organic pollutants, such as phenol, in a macroneutral buffer solution. An acidic microenvironment in the slipping plane of CoFe2O4 is successfully constructed by chemically bonding with MoS2. This microenvironment is not affected by the surrounding pH, which ensures the stable circulation of Fe3+/Fe2+ on the surface of CoFe2O4/MoS2 under neutral or even alkaline conditions. Additionally, CoFe2O4/MoS2 always exposes “fresh” active sites for the decomposition of H2O2 and the generation of 1O2, effectively inhibiting the production of iron sludge and enhancing the remediation of organic pollutants, even in actual wastewater. This work not only experimentally verifies the existence of an acidic microenvironment on the surface of heterogeneous catalysts for the first time, but also eliminates the pH limitation of the Fenton reaction for pollutant remediation, thereby expanding the applicability of Fenton technology.
We have successfully constructed an acidic microenvironment on the surface of CoFe2O4 by chemical bonding MoS2, which ensures the stable circulation of iron ions in the slipping plane and truly overcomes the limitation of pH in pollutant control, thereby expanding the applicability of Fenton technology.
COVID-19 has remained an uncontained, worldwide pandemic. While battling for the disease in China, six Traditional Chinese Medicine (TCM) recipes have been shown to be remarkably effective for ...treating patients with COVID-19. The present review discusses principles of TCM in curing infectious disease, and clinical evidence and mechanisms of the 6 most effective TCM recipes used in treating COVID-19 in 92% of all of the confirmed cases in China. Applications of TCM and specific recipes in the treatment of other viral infections, such as those caused by SARS-CoV, MERS-CoV, hepatitis B virus, hepatitis C virus, influenza A virus (including H1N1 and H7N9), influenza B, dengue virus as well as Ebola virus, are also discussed. Among the 6 TCM recipes, Jinhua Qinggan (JHQG) granules and Lianhua Qingwen (LHQW) capsules are recommended during medical observation; Lung Cleansing and Detoxifying Decoction (LCDD) is recommended for the treatment of both severe and non-severe patients; Xuanfeibaidu (XFBD) granules are recommended for treating moderate cases; while Huashibaidu (HSBD) and Xuebijing (XBJ) have been used in managing severe cases effectively. The common components and the active ingredients of the six TCM recipes have been summarized to reveal most promising drug candidates. The potential molecular mechanisms of the active ingredients in the six TCM recipes that target ACE2, 3CLpro and IL-6, revealed by molecular biological studies and/or network pharmacology prediction/molecular docking analysis/visualization analysis, are fully discussed. Therefore, further investigation of these TCM recipes may be of high translational value in enabling novel targeted therapies for COVID-19, potentially via purification and characterization of the active ingredients in the effective TCM recipes.
Objectives
Lymph node burden has been proposed to estimate the cumulative adverse effect of nodal metastasis. In this study, a meta‐analysis was conducted to evaluate the prognostic value of lymph ...node burden in oral cavity squamous cell carcinoma.
Study Designs
Systemic review and meta‐analysis.
Methods
PubMed, EMBASE and the Cochrane Library as well as manual searches were performed until April 2020. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival, disease‐specific survival, and disease‐free survival were extracted and pooled.
Results
Eleven included studies were published between 2009 and 2019. The cumulative number of patients was 20,607 (range 35–14,554). Extranodal extension was adjusted or evaluated in all of the studies. The meta‐analysis indicated that a higher lymph node burden was significantly related to worse overall survival (HR 2.62, 95% CI 2.12–3.25), worse disease‐specific survival (HR 3.14, 95% CI 1.85–5.33) and worse disease‐free survival (HR 2.30, 95% CI 1.62–3.26). The highest hazard ratio was observed when the cutoff value was 3 for overall survival, 3 for disease‐specific survival, and 4 for disease‐free survival. The hazard ratio showed an upward trend before the cutoff value of 3 but no significant incremental change when the cutoff exceeded 3.
Conclusions
In oral squamous cell carcinoma, lymph node burden is an independent prognosticator for survival outcomes. However, more prospective or high‐quality studies are required to determine the optimal cutoff.
Level of Evidence
NA Laryngoscope, 132:88–95, 2022
Late‐stage diversification of drug molecules is an important strategy in drug discovery that can be facilitated by reaction screening using high‐throughput experimentation. Here we present a rapid ...method for functionalizing bioactive molecules based on accelerated reactions in microdroplets. Reaction mixtures are nebulized at throughputs better than 1 reaction/second and the accelerated reactions occurring in the microdroplets are followed by desorption electrospray ionization mass spectrometry (DESI‐MS). Because the accelerated reactions occur on the millisecond timescale, they allow an overall screening throughput of 1 Hz working at the low nanogram scale. Using this approach, an opioid agonist (PZM21) and an antagonist (naloxone) were diversified using three reactions important in medicinal chemistry: sulfur fluoride exchange (SuFEx) click reactions, imine formation reactions, and ene‐type click reactions. Some 269 functionalized analogs of naloxone and PZM21 were generated and characterized by tandem mass spectrometry (MS/MS) after screening over 500 reactions.
High‐throughput late‐stage functionalization of complex molecules was achieved using an automated platform based on desorption‐electrospray‐ionization mass spectrometry. Accelerated reactions in microdroplets enable the ultrafast synthesis of diversified drug molecules. Over 250 analogues of bioactive compounds were generated and characterized using nanogram amounts of material in less than 1 second per reaction.
Objective To analyze and compare the effects of transverse ligament injury on the stability and stress distribution of atlantoaxial complex fractures using 3D finite element method. Methods A male ...volunteer with a normal cervical spine was selected. The cranio-cervical region (C0-C3) was scanned using a 64-slice spiral CT scanner. Software such as Simpleware 3.0, Geomagic 12.0, and Hypermesh 12.0 were used to create a three-dimensional finite element model (FEM/Intact) of the C0-C3 segment. On the validated model, the anterior and posterior arches of C1 and the base of the odontoid process were fractured to create a composite fracture model (FEM/Fracture) simulating Jefferson/Type Ⅱ odontoid fracture. Two additional models were created: one with a ruptured transverse ligament of the atlas (FEM/RTL) and another with an intact transverse ligament (FEM/TL). The models were subjected to loading conditions of flexion, extension, lateral bending, and rotation, and the Von Mises stress distribution and vertebral seg
Memristive devices have been extensively demonstrated for applications in nonvolatile memory, computer logic, and biological synapses. Precise control of the conducting paths associated with the ...resistance switching in memristive devices is critical for optimizing their performances including ON/OFF ratios. Here, gate tunability and multidirectional switching can be implemented in memristors for modulating the conducting paths using hexagonal α‐In2Se3, a semiconducting van der Waals ferroelectric material. The planar memristor based on in‐plane (IP) polarization of α‐In2Se3 exhibits a pronounced switchable photocurrent, as well as gate tunability of the channel conductance, ferroelectric polarization, and resistance‐switching ratio. The integration of vertical α‐In2Se3 memristors based on out‐of‐plane (OOP) polarization is demonstrated with a device density of 7.1 × 109 in.−2 and a resistance‐switching ratio of well over 103. A multidirectionally operated α‐In2Se3 memristor is also proposed, enabling the control of the OOP (or IP) resistance state directly by an IP (or OOP) programming pulse, which has not been achieved in other reported memristors. The remarkable behavior and diverse functionalities of these ferroelectric α‐In2Se3 memristors suggest opportunities for future logic circuits and complex neuromorphic computing.
Gate‐tunable and multidirection‐switchable memristive phenomena in a van der Waals ferroelectric α‐In2Se3 are demonstrated. The planar memristor exhibits a pronounced switchable photocurrent, as well as gate tunability of the channel conductance, ferroelectric polarization, and resistance‐switching ratio. A multidirectionally operated α‐In2Se3 memristor is also proposed, enabling the control of the out‐of‐plane (OOP) (or in‐plane (IP)) resistance state directly by an IP (or OOP) programming pulse.
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