Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct ...disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.
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•First deep proteogenomic landscape of non-smoking lung adenocarcinoma in East Asia•Identified age, sex-related endogenous, and environmental carcinogen mutagenic processes•Proteome-informed classification distinguished clinical features within early stages•Protein networks identified tumorigenesis hallmarks, biomarkers, and druggable targets
Deep proteogenomic landscape of early stage lung adenocarcinoma in a cohort of mostly non-smokers reveals unique drivers and biomarkers, as well as gender-associated mutagenesis.
The electrochemical N2 fixation, which is far from practical application in aqueous solution under ambient conditions, is extremely challenging and requires a rational design of electrocatalytic ...centers. We observed that bismuth (Bi) might be a promising candidate for this task because of its weak binding with H adatoms, which increases the selectivity and production rate. Furthermore, we successfully synthesized defect‐rich Bi nanoplates as an efficient noble‐metal‐free N2 reduction electrocatalyst via a low‐temperature plasma bombardment approach. When exclusively using 1H NMR measurements with N2 gas as a quantitative testing method, the defect‐rich Bi(110) nanoplates achieved a 15NH3 production rate of 5.453 μg mgBi−1 h−1 and a Faradaic efficiency of 11.68 % at −0.6 V vs. RHE in aqueous solution at ambient conditions.
Beneficial defects: Defect‐rich bismuth nanoplates achieve a 15NH3 production rate of 5.453 μg mgBi−1 h−1 and a Faradaic efficiency of 11.68 % at −0.6 V vs. RHE in aqueous solutions at ambient conditions because of their poor binding with H adatoms, which increases the selectivity and production rate. Also, 1H NMR measurements with N2 gas ware used as a quantitative test method in aqueous electrolytes.
A pandemic of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. ...We conducted a retrospective, multicenter study, and followed‐up with all children from the families with SARS‐CoV‐2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS‐CoV‐2 RNA with real‐time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal‐viral excretion times among groups with different antiviral regiments were compared with Kaplan‐Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS‐CoV‐2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty‐three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS‐CoV‐2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal‐viral‐excreting children. Children have lower susceptibility of SARS‐CoV‐2 infection, longer incubation, and fecal‐viral excretion time. Positive results of fecal SARS‐CoV‐2 RNA detection were not used as indication for hospitalization or quarantine.
Highlights
Children had lower susceptibility for SARS‐CoV‐2 infection than adults.
Children had longer incubation period and fecal viral excretion time after infected by SARS‐CoV‐2.
Viral clearance time was not different among the groups treated with different antiviral regiments.
Children had milder clinical symptoms, better clinical outcome, and more common fecal viral excretion.
Positive results of fecal SARS‐CoV‐2 RNA detection are not used as indication for hospitalization or quarantine.
The development of new or more sustainable, active, efficient, controlled, and selective polymerization reactions or processes continues to be crucial for the synthesis of important polymers or ...materials with specific structures or functions. In this context, the newly emerged polymerization technique enabled by main-group Lewis pairs (LPs), termed as Lewis pair polymerization (LPP), exploits the synergy and cooperativity between the Lewis acid (LA) and Lewis base (LB) sites of LPs, which can be employed as frustrated Lewis pairs (FLPs), interacting LPs (ILPs), or classical Lewis adducts (CLAs), to effect cooperative monomer activation as well as chain initiation, propagation, termination, and transfer events. Through balancing the Lewis acidity, Lewis basicity, and steric effects of LPs, LPP has shown several unique advantages or intriguing opportunities compared to other polymerization techniques and demonstrated its broad polar monomer scope, high activity, control or livingness, and complete chemo- or regioselectivity, as well as its unique application in materials chemistry. These advances made in LPP are comprehensively reviewed, with the scope of monomers focusing on heteroatom-containing polar monomers, while the polymerizations mediated by main-group LAs and LBs separately that are most relevant to the LPP are also highlighted or updated. Examples of applying the principles of the LPP and LP chemistry as a new platform for advancing materials chemistry are highlighted, and currently unmet challenges in the field of the LPP, and thus the suggested corresponding future research directions, are also presented.
Abstract
Background
Degenerative osteoarthritis (OA) often leads to pain and stiffness of the affected joints, which may affect the physical performance and decrease the quality of life of people ...with degenerative knee OA. Compared to traditional exercise, tai chi is a safe exercise with slow movements which can facilitate physical functioning and psychological well being, and might be suitable for improving the physical activities of older adults with knee OA. Therefore, this study investigated the impacts of tai chi exercise on the functional fitness of community-dwelling older adults with degenerative knee OA.
Methods
Sixty-eight community-dwelling older adults with knee OA were recruited from the local community to participate in this randomized controlled clinical trial. All subjects were randomly assigned to either an TCE group that practiced tai chi exercise (TCE) (
n
= 36) or a control group (CON) (
n
= 32) that received regular health education programs twice per week for 12 weeks. Outcome measurements were determined using functional fitness tests before and after the intervention, including a 30-s chair stand (number of repeats), 30-s arm-curl (number of repeats), 2-min step (number of steps), chair sit-and-reach (reaching distance, cm), back-scratch flexibility (distance between hands, cm), single-leg stand (time, s), functional reach (reaching distance, cm), 8-foot up-and-go (time, s), and 10-m walk tests (time, s). Pre-post comparisons of functional fitness were analyzed using the ANCOVA test with SPSS software version 18.0.
Results
Results revealed that participants’ functional fitness in the TCE group had significantly higher adjusted mean post-tests scores than that in the CON group after the intervention, including the 8-foot up-and-go (s) (mean difference MD=-2.92 -3.93, -1.91,
p
= 2.39*10
− 7
), 30-s arm curl (MD = 4.75 (2.76, 6.73),
p
= 1.11*10
− 5
), 2-min step (MD = 36.94 23.53, 50.36,
p
= 7.08*10
− 7
), 30-s chair stand (MD = 4.66 2.97, 6.36,
p
= 6.96*10
− 7
), functional-reach (MD = 5.86 3.52, 8.20,
p
= 4.72*10
− 6
), single-leg stand with eyes closed (MD = 3.44 1.92, 4.97,
p
= 2.74*10
− 5
), chair sit-and-reach (MD = 3.93 1.72, 6.15,
p
= 0.001), and single-leg stand with eyes opened (MD = 17.07 6.29, 27.85,
p
= 0.002), with large effect sizes (η²=0.14 ~ 0.34).
Conclusions
Community-dwelling older adults with knee OA in the TCE group had better functional fitness performances after the 12-week tai chi intervention than those receiving only health education.
Because of the absence of methods for tracking RNA G‐quadruplex dynamics, especially the folding and unfolding of this attractive structure in live cells, understanding of the biological roles of RNA ...G‐quadruplexes is so far limited. Herein, we report a new red‐emitting fluorescent probe, QUMA‐1, for the selective, continuous, and real‐time visualization of RNA G‐quadruplexes in live cells. The applications of QUMA‐1 in several previously intractable applications, including live‐cell imaging of the dynamic folding, unfolding, and movement of RNA G‐quadruplexes and the visualization of the unwinding of RNA G‐quadruplexes by RNA helicase have been demonstrated. Notably, our real‐time results revealed the complexity of the dynamics of RNA G‐quadruplexes in live cells. We anticipate that the further application of QUMA‐1 in combination with appropriate biological and imaging methods to explore the dynamics of RNA G‐quadruplexes will uncover more information about the biological roles of RNA G‐quadruplexes.
Flexing 'plexes: A new fluorescent probe, QUMA‐1, for the selective, continuous, and real‐time imaging of RNA G‐quadruplexes in live cells is reported. The use of QUMA‐1 in previously inaccesible applications, including live‐cell imaging of RNA G‐quadruplex dynamics and the visualization of the unwinding of RNA G‐quadruplexes by RNA helicase is demonstrated.
The current practices in the generation and disposal of synthetic polymers are largely unsustainable. As part of the solution, the development of biodegradable polymers, which constitute a class of ..."green polymers" according to green chemistry principles, has been intensively pursued in the past two decades. However, the degradation of such polymers in Earth's landfills typically leads to no recovery of the materials' value, and their degradation in the Oceans could create new or unintended environmental consequences. Industrial mechanical recycling always suffers from a significant quality loss. The proposed more sustainable solution is to develop chemically recyclable polymers that not only solve the end-of-life issue of polymers, but also provide a direct approach to establish a circular materials economy. Accordingly, this critical review article captures some selected highlights of the emerging area of recyclable "green polymers" by focusing on the major progress made and the technical and environmental benefits obtained in the development of repurposing and depolymerization processes for chemical recycling of polymers at the end of their useful life.
Developing recyclable polymers provides a solution to materials' end-of-life issues and also an approach to establish a circular materials economy.
Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the ...effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.
The field of next‐generation microdisplays is flourishing. Relevant display technologies, such as mini‐light emission diodes (mini‐LEDs), micro‐organic light emission diodes (micro‐OLEDs), and ...micro‐light emission diodes (micro‐LEDs) are thus in the urgent stage of development. From this perspective, comprehensive and systematical analyzes are conducted for the aforesaid microdisplay configurations. A holistic view of microdisplay technologies is developed with the corresponding performance metrics, providing a path for miscellaneous scenarios. Among these scenarios, the applications in augmented reality (AR), virtual reality (VR), wearable devices, and head‐up displays (HUD) are currently attracting considerable attention for deeper human‐digital interactions. However, there is a multiplicity of obstacles and challenges hindering such development. Nevertheless, recent advances in microdisplay technologies hold tremendous promise for the paradigms of these applications, taking a leap forward for next‐generation microdisplays. This review presents perspectives, relevant materials, and the technology landscape for such ongoing display technologies, offering guidance on the design of advanced microdisplays.
The demand for augmented reality (AR), virtual reality (VR), wearables, and head‐up display (HUD) technology has fueled the rapid growth of next‐generation microdisplays. Despite their promise, challenges remain. This review analyzes performance metrics across various scenarios and provides valuable materials and technology perspectives for ongoing display technology. Our guidance for advanced microdisplay design aims to overcome obstacles and improve the field.
Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this ...study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient‐Generated Subjective Global Assessment (PG‐SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4‐nitroquinoline 1‐oxide (4NQO)‐induced tongue tumor animal model. Our data revealed that malnutrition (high PG‐SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG‐SGA scores had a higher neutrophil‐to‐lymphocyte ratio, higher proportion of myeloid‐derived suppressor cells (MDSCs), and elevated IL‐6 levels in the peripheral circulation. Patients with increased PG‐SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO‐induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune‐suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL‐6 expression. In conclusion, malnutrition by PG‐SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO‐tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.
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