The rapid development of topological photonics and acoustics calls for accurate understanding of band topology in classical waves, which is not yet achieved in many situations. Here, we present the ...Wilson-loop approach for exact numerical calculation of the topological invariants for several photonic/sonic crystals. We demonstrate that these topological photonic/sonic crystals are topological crystalline insulators with fragile topology, a feature which has been ignored in previous studies. We further discuss the bulk-edge correspondence in these systems with emphasis on symmetry broken on the edges.
Inner filter effect (IFE) was previously considered as an error in fluorescence measurement. In recent years, it has been developed as an important non-irradiation energy conversion model of ...spectroscopic technique and found wide applications in the fields of chemical sensing and biosensing. In comparison with traditional techniques based on forster resonance energy transfer (FRET), the IFE-based fluorescent approach is more flexible and straightforward without the link of absorber with fluorescer. The present review for the first time introduces the state of the art in the progress of the IFE-based fluorescent sensing systems, including sensing strategy, essential conditions, materials option, and their applications for the detection of various target analytes, e.g., ionic species, small molecules, and macromolecules. In addition, the benefits and limitations of the IFE-based fluorescent sensing systems are also critically discussed and highlighted.
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•Inner filter effect in the application of sensing field.•The fundamental, essential conditions and material option of IFE-based sensing.•Critical applications of IFE-based sensing systems for various target analytes.•The benefits/limitations and perspectives of IFE-based sensing.
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to ...increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano‐sized vesicles released by a variety of cells. Emerging evidence shows that ...exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life‐threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome‐delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti‐cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti‐cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.
Exosomes are nano‐sized vesicles released by a variety of cells. Exosomes function as versatile promoters in the tumorigenesis, metastasis and drug resistance of breast cancer. In this review, we summarize the current knowledge about the functions of exosomes in the diagnosis, tumorigenesis, metastasis, microenvironment, drug resistance and therapy of breast cancer.
Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial ...resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.
Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ ...dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words “pyro” and “ptosis” in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.
Neuroinflammation has been reported to be associated with Alzheimer's disease (AD) pathogenesis. Neuroinflammation is generally considered as an outcome of glial activation; however, we recently ...demonstrated that T helper (Th)17 cells, a subpopulation of proinflammatory CD4+ T cells, are also involved in AD pathogenesis. Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, can be immunosuppressive, but its effects on lymphocyte-mediated neuroinflammation in AD pathogenesis have not been well addressed. In the current study we administered TGF-β1 via intracerebroventricle (ICV) and intranasal (IN) routes in AD model rats to investigate its antiinflammatory and neuroprotective effects. The AD rat model was prepared by bilateral hippocampal injection of amyloid-β (Aβ)1-42. TGF-β1 was administered via ICV one hour prior to Aβ1-42 injection or via both nares seven days after Aβ1-42 injection. ICV administration of TGF-β1 before Aβ1-42 injection remarkably ameliorated Aβ1-42-induced neurodegeneration and prevented Aβ1-42-induced increases in glia-derived proinflammatory mediators (TNF-α, IL-1β and iNOS), as well as T cell-derived proinflammatory cytokines (IFN-γ, IL-2, IL-17 and IL-22), in the hypothalamus, serum or cerebrospinal fluid (CSF) in a concentration-dependent manner. TGF-β1 pretreatment also prevented Aβ1-42-induced decreases in the neurotrophic factors, IGF-1, GDNF and BDNF, and in the antiinflammatory cytokine, IL-10. Similarly, IN administration of TGF-β1 after Aβ1-42 injection reduced neurodegeneration, elevation of proinflammatory mediators and cytokines, and reduction of neurotrophic and antiinflammatory factors, in the hypothalamus, serum or CSF. These findings suggest that TGF-β1 suppresses glial and T cell-mediated neuroinflammation and thereby alleviates AD-related neurodegeneration. The effectiveness of IN administered TGF-β1 in reducing Aβ1-42 neurotoxicity suggests a possible therapeutic approach in patients with AD.
Summary Background The mcr-1 gene confers transferable colistin resistance. mcr-1 -positive Enterobacteriaceae (MCRPE) have attracted substantial medical, media, and political attention; however, so ...far studies have not addressed their clinical impact. Herein, we report the prevalence of MCRPE in human infections and carriage, clinical associations of mcr-1 -positive Escherichia coli (MCRPEC) infection, and risk factors for MCRPEC carriage. Methods We undertook this study at two hospitals in Zhejiang and Guangdong, China. We did a retrospective cross-sectional assessment of prevalence of MCRPE infection from isolates of Gram-negative bacteria collected at the hospitals from 2007 to 2015 (prevalence study). We did a retrospective case-control study of risk factors for infection and mortality after infection, using all MCRPEC from infection isolates and a random sample of mcr-1 -negative E coli infections from the retrospective collection between 2012 and 2015 (infection study). We also did a prospective case-control study to assess risk factors for carriage of MCRPEC in rectal swabs from inpatients with MCRPEC and mcr-1 negative at the hospitals and collected between May and December, 2015, compared with mcr-1 -negative isolates from rectal swabs of inpatients (colonisation study). Strains were analysed for antibiotic resistance, plasmid typing, and transfer analysis, and strain relatedness. Findings We identified 21 621 non-duplicate isolates of Enterobacteriaceae, Acinetobacter spp, and Pseudomonas aeruginosa from 18 698 inpatients and 2923 healthy volunteers. Of 17 498 isolates associated with infection, mcr-1 was detected in 76 (1%) of 5332 E coli isolates, 13 (<1%) of 348 Klebsiella pneumoniae , one (<1%) of 890 Enterobacter cloacae , and one (1%) of 162 Enterobacter aerogenes . For the infection study, we included 76 mcr-1 -positive clinical E coli isolates and 508 mcr-1 -negative isolates. Overall, MCRPEC infection was associated with male sex (209 41% vs 47 63%, adjusted p=0·011), immunosuppression (30 6% vs 11 15%, adjusted p=0·011), and antibiotic use, particularly carbapenems (45 9% vs 18 24%, adjusted p=0·002) and fluoroquinolones (95 19% vs 23 30%, adjusted p=0·017), before hospital admission. For the colonisation study, we screened 2923 rectal swabs from healthy volunteers, of which 19 were MCRPEC, and 1200 rectal swabs from patients, of which 35 were MCRPEC. Antibiotic use before hospital admission (p<0·0001) was associated with MCRPEC carriage in 35 patients compared with 378 patients with mcr-1-negative E coli colonisation, whereas living next to a farm was associated with mcr-1-negative E coli colonisation (p=0·03, univariate test). mcr-1 could be transferred between bacteria at high frequencies (10−1 to 10−3 ), and plasmid types and MCRPEC multi-locus sequence types (MLSTs) were more variable in Guangdong than in Zhejiang and included the human pathogen ST131. MCRPEC also included 17 unreported ST clades. Interpretation In 2017, colistin will be formally banned from animal feeds in China and switched to human therapy. Infection with MRCPEC is associated with sex, immunosuppression, and previous antibiotic exposure, while colonisation is also associated with antibiotic exposure. MLST and plasmid analysis shows that MCRPEC are diversely spread throughout China and pervasive in Chinese communities. Funding National Key Basic Research Program of China, National Natural Science Foundation of China/Zhejiang, National Key Research and Development Program, and MRC, UK.
Chronic obstructive pulmonary disease (COPD) is an intractable disease involving a sticky mucus layer and nanoagents with mucus‐penetrating capability offer a new way to deliver drugs. However, drug ...release from nanovehicles requires optimization to enhance the therapeutic effects of COPD therapy. Herein, black phosphorus quantum dots (BPQDs) are combined with PEGylated chitosan nanospheres containing the antibiotic amikacin (termed PEG@CS/BPQDs‐AM NPs). As a drug‐delivery system, the hydrophilicity of PEG and positive charge of CS facilitate the penetration of nanovehicles through the mucus layer. The nanovehicles then adhere to the mucous membrane. Furthermore, the BPQDs degrade rapidly into nontoxic PO43− and acidic H+, thereby promoting the dissociation of PEGylated CS nanospheres, accelerating the release of AM, decreasing the vitality of biofilms for ease of eradication. Our results reveal that drug delivery mediated by BPQDs is a feasible and desirable strategy for precision medicine and promising for the clinical therapy of COPD.
A mucus‐penetrating drug‐delivery strategy is designed for the efficient therapy of chronic obstructive pulmonary disease (COPD). After pulmonary aspiration, nanovehicles can penetrate the mucus barrier and adhere onto the mucous membrane. Subsequently, the nanovehicle degrades via the oxidative degradation of BPQDs, releasing the antibiotic amikacin. This suggests that BPQD‐mediated drug release offers a feasible strategy for precision medicine.
Point-of-care testing (POCT) with the advantages of simplicity, rapidity, portability, and low-cost is of great importance to improve healthcare, especially in resource-limited settings and home ...healthcare settings. Moreover, it is a great challenge to quantitative POCT of multiplexed biomarkers within a single accessible assay but provides enhanced diagnostic accuracy and improved diagnostic efficiency. Herein, a smartphone optical device has been designed for POCT of glucose and cholesterol in metabolic syndrome patients using a ratiometric fluorescent sensor. The sensing system of Ag NPs/UiO-66-NH2 and o-phenylenediamine presents a dual-emission response to H2O2 (the main product of glucose and cholesterol catalyzed by glucose oxidase and cholesterol oxidase) on account of the inner filter effect, resulting in an increase in the response of the fluorescence intensity ratio (F 555 nm/F 425 nm) accompanied by a distinguishable color transition from blue to yellow green. After compositing probes with a flexible substrate, the obtained test strip can be integrated with a smartphone-based portable platform to read RGB values for accurate testing of glucose and cholesterol with both detection limits of 10 μmol L–1, which are hundreds of times lower than their concentrations in human serum. With the advantages of low-cost, ease of operation, and broad adaptability, this smartphone optical device holds great potential for portable detection of numerous targets in personalized healthcare and clinical diagnosis.
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