Optical Imaging of Single Extracellular Vesicles: Recent Progress and Prospects.

Extracellular vesicles (EVs) are small, membrane-bound structures released by various cell types into the extracellular environment, which play a crucial role in intercellular communication and the transfer of biomolecules between cells. Given their functional significance, there are intense research interests to use EVs as disease markers and drug carriers. However, EVs characterization is greatly hindered by the small size, the low biomolecule payload, and the high level of heterogeneity.

Recent Advances in Fluorescent Nanoparticles for Stimulated Emission Depletion Imaging.

Stimulated emission depletion (STED) microscopy, as a popular super-resolution imaging technique, has been widely used in bio-structure analysis and resolving the dynamics of biological processes beyond the diffraction limit. The performance of STED critically depends on the optical properties of the fluorescent probes. Ideally, the probe should process high brightness and good photostability, and exhibit a sensitive response to the depletion beam.

DNA Molecular Glue Assisted Bacterial Conjugative Transfer.

Bacterial conjugation, a commonly used method to horizontally transfer functional genes from donor to recipient strains, plays an important role in the genetic manipulation of bacteria for basic research and industrial production. Successful conjugation depends on the donor-recipient cell recognition and a tight mating junction formation. However, the efficiency of conjugative transfer is usually very low.

Monodispersed and Monofunctionalized DNA-Caged Au Nano-Clusters with Enhanced Optical Properties for STED Imaging.

The performance of Stimulated Emission Depletion (STED) microscopy depends critically on the fluorescent probe. Ultrasmall Au nanoclusters (Au NCs) exhibit large Stokes shift, and good stimulated emission response, which are potentially useful for STED imaging. However, Au NCs are polydispersed in size, sensitive to the surrounding environment, and difficult to control surface functional group stoichiometry, which results in reduced density and high heterogeneity in the labeling of biological structures.

The study of the role of purified anti-mouse CD193 (CCR3) antibody in allergic rhinitis mouse animal models.

The pathogenesis of allergic asthma is similar to that of allergic rhinitis, with inflammation cells producing and releasing inflammatory mediators and cytokines closely related to CCR3.Based on the theory of "one airway, one disease", the use of CCR3 monoclonal antibody may have a similar effect on allergic rhinitis. However, there are few studies on CCR3 monoclonal antibody in allergic rhinitis.

Ultrasensitive Point-of-Care Detection of Protein Markers Using an Aptamer-CRISPR/Cas12a-Regulated Liquid Crystal Sensor (ALICS).

Despite extensive efforts, point-of-care testing (POCT) of protein markers with high sensitivity and specificity and at a low cost remains challenging. In this work, we developed an aptamer-CRISPR/Cas12a-regulated liquid crystal sensor (ALICS), which achieved ultrasensitive protein detection using a smartphone-coupled portable device. Specifically, a DNA probe that contained an aptamer sequence for the protein target and an activation sequence for the Cas12a-crRNA complex was prefixed on a substrate and was released in the presence of target.

Bioactive Isoquinoline Alkaloids with Diverse Skeletons from .

Six new isoquinoline alkaloids, including aporphine alkaloids (, , , and ), a benzylisoquinoline alkaloid (), and a protoberberine alkaloid (), were isolated from the roots of , along with a new furanone () and 13 known isoquinoline alkaloids (, -, , , -, , and ). The structures of the new compounds were elucidated by the analysis of spectroscopic data. Compounds and are rare oxalyl-fused dehydroaporphine alkaloids.

Multi-parameter Inputted Logic-Gating on Aptamer-Encoded Extracellular Vesicles for Colorectal Cancer Diagnosis.

Extracellular vesicles (EVs) have emerged as a potential biomarker in liquid biopsy. However, cancer heterogeneity poses significant challenge to precise molecular diagnosis based on single-parameter input. Hence, strategies for analyzing multiple inputs with molecular computing were developed with the aim of improving diagnostic accuracy in liquid biopsy.

Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples.

Sensitive and specific blood-based assays for the detection of pulmonary and extrapulmonary tuberculosis would reduce mortality associated with missed diagnoses, particularly in children. Here we report a nanoparticle-enhanced immunoassay read by dark-field microscopy that detects two Mycobacterium tuberculosis virulence factors (the glycolipid lipoarabinomannan and its carrier protein) on the surface of circulating extracellular vesicles. In a cohort study of 147 hospitalized and severely immunosuppressed children living with HIV, the assay detected 58 of the 78 (74%) cases of paediatric tuberculosis, 48 of the 66 (73%) cases that were missed by microbiological assays, and 8 out of 10 (80%) cases undiagnosed during the study.

Real-Life Experience of Regorafenib in Patients With Advanced Hepatocellular Carcinoma.

The RESORCE trial reported that regorafenib was effective as the second-line treatment for patients with hepatocellular carcinoma (HCC) after progression on sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice. We aimed to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC.

Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine.

Multidrug resistance (MDR) has become one of the most intractable problems in clinics as it would cause failure in chemotherapy. In this study, we demonstrated that a nanoscale self-assembled nanomedicine, which almost consisted of a pure chemo-drug, could efficiently overcome MDR. Celastrol (CST) was directly assembled into a discrete nanomedicine by precipitation, and then CST nanoparticles (CNPs) inhibited drug efflux pumps by activating HSF-1 expression and promoting HSF-1 translocation into nucleus to suppress the Pgp expression.

Liver resection for large and huge hepatocellular carcinoma: Predictors of failure, recurrence patterns, and prognoses.

Background: Characteristic symptoms and signs are often absent in patients with hepatocellular carcinoma (HCC). As a result, many patients are not diagnosed until their tumors have grown to large (> 5cm) or huge sizes (> 10cm). Liver resection has traditionally been reserved for patients with small HCC, but more recently it is being used for patients with large and huge tumors.

Experimental study of β-TCP scaffold loaded with VAN/PLGA microspheres in the treatment of infectious bone defects.

Antibiotic bone cement filling technology has been widely used in the treatment of infectious bone defects for decades. However, the current treatment requires multiple complicated procedures, which would lead to pain and financial burden for patients. Repairing bone defects and control infection at the same time is the pain spot of orthopaedic area.

Transcriptional Regulator YqeI, Locating at ETT2 Locus, Affects the Pathogenicity of Avian Pathogenic .

Avian pathogenic (APEC) is the leading cause of systemic infections in poultry worldwide and has a hidden threat to public health. type three secretion system 2 (ETT2), similar to the pathogenicity island SPI1, is widely distributed in APEC and associated with virulence. The function of YqeI, which is one of the hypothetical transcriptional regulators locating at the ETT2 locus of APEC, is unknown.

Gd-Metallofullerenol nanoparticles cause intracellular accumulation of PDGFR-α and morphology alteration of fibroblasts.

Gadolinium-metallofullerenols (Gd@C82(OH)22) are a promising agent for cancer therapy and have shown beneficial effects in regulating the tumor microenvironment with low toxicity. However, the underlying mechanism by which Gd@C82(OH)22 interacts with fibroblasts remains unclear. In order to explore the critical role that activated fibroblasts play in tumorigenesis and fibrosis, we investigated the regulatory effect of Gd@C82(OH)22 in fibroblast activation and oncogenic transformation, and found that the PDGFR-α is an essential molecule in modulating the morphology and functional changes in fibroblasts after Gd@C82(OH)22 treatment.

Synergistic combination chemotherapy using carrier-free celastrol and doxorubicin nanocrystals for overcoming drug resistance.

A key challenge of chemotherapy in clinical treatments is multidrug resistance (MDR), which mainly arises from drug efflux-induced tumor cell survival. Thus, it is necessary to provide biocompatible chemotherapeutics to improve drug accumulation in MDR cells. Herein, two clinical small molecular drugs, celastrol (CST) and doxorubicin (DOX), were self-assembled into carrier-free and biocompatible nanoparticles (CST/DOX NPs) via a simple and green precipitation method for synergistic combination chemotherapy to overcome DOX resistance.

Immobilized Ferrous Ion and Glucose Oxidase on Graphdiyne and Its Application on One-Step Glucose Detection.

Graphdiyne (GDY) is a novel two-dimensional (2D) carbon allotrope with sp-hybridized carbon atoms and hexagonal rings. Because of its unique structure and electronic property, GDY was reported as a promising candidate applied in energy storage, catalysis, biosensing and so on. However, using GDY as a platform to immobilize metal ion or enzyme was still not reported.

Poly(lactic-co-glycolic acid)/Polycaprolactone Nanofibrous Membranes for High-Efficient Capture of Nano- and Microsized Particulate Matter.

The incidence of many diseases is closely related to air pollution. Suspended particulate matter of different sizes represents a major source of environmental pollution. Fine particles, especially ultrafine particles smaller than 2.

Direct site-specific treatment of skin cancer using doxorubicin-loaded nanofibrous membranes.

Doxorubicin (DOX) is widely used in cancer therapy. However, its application is sometimes limited by its adverse cardiotoxicity and delivery pathways. In our study, we prepared a topical implantable delivery device for controlled drug release and site-specific treatment.

Mirror-Image Thymidine Discriminates against Incorporation of Deoxyribonucleotide Triphosphate into DNA and Repairs Itself by DNA Polymerases.

DNA polymerases are known to recognize preferably d-nucleotides over l-nucleotides during DNA synthesis. Here, we report that several general DNA polymerases catalyze polymerization reactions of nucleotides directed by the DNA template containing an l-thymidine (l-T). The results display that the 5'-3' primer extension of natural nucleotides get to the end at chiral modification site with Taq and Phanta Max DNA polymerases, but the primer extension proceeds to the end of the template catalyzed by Deep Vent (exo), Vent (exo), and Therminator DNA polymerases.

PH-Dependent Enantioselectivity of D-amino Acid Oxidase in Aqueous Solution.

D-amino acid oxidases (DAAO) are stereospecific enzymes which are generally almost inactive towards L-enantiomer in neutral solution when L-, D-amino acids are supplied as substrates. In this paper, the D-amino acid oxidase can catalytic oxidize L-amino acids by modulating pH of aqueous solution. With L-Pro as substrate, the catalytic rate (k ) and the affinity (K ) of DAAO were 6.

Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis inhibition of NF-κB.

Chicoric acid (CA), a natural phenolic acid extracted from chicory and the echinacea (purple coneflower) plant (), has been regarded as a nutraceutical that has powerful antioxidant and antiobesity activities. We investigated the inhibitory effects of CA on systemic inflammation-induced neuroinflammation, amyloidogenesis, and cognitive impairment. C57BL/6J mice were treated with 0.