Homogeneous, Simple, and Direct Analysis of Exosomal PD-L1 via Aptamer-Bivalent-Cholesterol-Anchor Assembly of DNAzyme (ABCzyme) for Tumor Immunotherapy.

Breakthroughs in immune checkpoint inhibitor (ICI) therapy have revolutionized clinical tumor therapy. Immunohistochemistry (IHC) analysis of PD-L1 in tumor tissue has been used to predict the response to tumor immunotherapy, but the results are not reproducible, and IHC is invasive and cannot be used to monitor the dynamic changes in PD-L1 expression during treatment. Monitoring the expression level of the PD-L1 protein on exosomes (exosomal PD-L1) is promising for both tumor diagnosis and tumor immunotherapy. Here, we established an aptamer-bivalent-cholesterol-anchor assembly of DNAzyme (ABCzyme) analytical strategy that can directly detect exosomal PD-L1 with a minimum lower limit of detection of 5.21 pg/mL. In this way, we found that the levels of exosomal PD-L1 are significantly elevated in the peripheral blood of patients with progressive disease. The precise analysis of exosomal PD-L1 by the proposed ABCzyme strategy provides a potentially convenient method for the dynamic monitoring of tumor progression in patients who receive immunotherapy and proves to be a potential and effective liquid biopsy method for tumor immunotherapy.

Current non-invasive strategies for brain drug delivery: overcoming blood-brain barrier transport.

BACKGROUND: The blood-brain barrier (BBB) is a complex and dynamic structure that serves as a gatekeeper, restricting the migrations of most compounds and molecules from blood into the central nervous system (CNS). The BBB plays a crucial role in maintaining CNS physiological function and brain homeostasis. It can protect the CNS from the entrance of toxic and infectious agents, however, it also restricts the drug permeation into brain to play a therapeutic role. The BBB has been the biggest limiting hurdle to medications entering the brain excluding from the brain about 100% of large-molecule and more than 98% of all small-molecule neurotherapeutics. As a result, it is of inability for drug molecule to reach requisite concentrations within the brain. OBJECTIVE: With the aim of enhancing drug permeability and efficacy, a variety of strategies have been developed: invasive approaches, such as intraarterial delivery, intrathecal delivery, or administrating directly the drug intraventricularly and intracerebrally; non-invasive approaches that take advantage of innate BBB functions, using prodrugs, focused ultrasound, intranasal administration or nanotechnology. CONCLUSIONS: Here we mainly review recent developments and challenges related to non-invasive BBB-crossing techniques, whose benefits include higher efficacy, easier application, less treatment burden, better patient acceptability, and adherence. Additionally, we also analyze the potential of non-invasive methods in the treatment of CNS disorders and render them as a most suitable platform for the management of neurological diseases.

Deep ultraviolet high-resolution microscopic hyperspectral imager and its biological tissue detection.

Ultraviolet (UV) hyperspectral imaging technology is commonly used in the field of atmospheric remote sensing. In recent years, some in-laboratory research has been carried out for substance detection and identification. In this paper, UV hyperspectral imaging technology is introduced into microscopy to better utilize the obvious absorption characteristics of components, such as proteins and nucleic acids in biological tissues in the ultraviolet band. A deep UV microscopic hyperspectral imager based on the Offner structure with F # 2.5, low spectral keystone and smile is designed and developed. A 0.68 numerical aperture microscope objective is designed. The spectral range of the system is from 200 nm to 430 nm; the spectral resolution is better than 0.5 nm; and the spatial resolution is better than 1.3 µm. The K562 cells can be distinguished by transmission spectrum of nucleus. The UV microscopic hyperspectral image of the unstained mouse liver slices showed similar results to the microscopic image after hematoxylin and eosin staining, which could help to simplify the pathological examination process. Both results show a great performance in spatial and spectral detecting capabilities of our instrument, which has the potential for biomedical research and diagnosis.

Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission.

ABSTRACT: Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H2S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H2S ameliorates transforming growth factor-ß1 (TGF-ß1)-induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H2S treatment dramatically suppressed TGF-ß1-induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H2S reversed TGF-ß1-induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1-dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H2S attenuates TGF-ß1-induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1-dependent fashion.

Wideband, high spectral resolution UV convex grating imaging spectrometer based on an Offner structure.

Ultraviolet is an effective electromagnetic spectrum in material detection, which has wide application prospects in aerospace and environmental monitoring. A conventional imaging spectrometer has a narrow UV band and low spectral resolution. To solve this problem, a convex grating imaging spectrometer based on an Offner structure with F#2.5 and a 13 mm long slit was designed and developed. The working wavelength ranges from 200 to 433 nm, and the spectral resolution is greater than 0.5 nm. A hyperspectral data cube with both high spatial and spectral resolutions of external scenes can be obtained by the push-broom imaging mode. Fine Fraunhofer lines can be distinguished in the spectrum. The ultraviolet hyperspectral imager can be used for marine oil spills, trace gas monitoring, and other applications that require high signal-to-noise ratios, wide bands, and high spectral resolutions.

Underwater hyperspectral imaging system with dual-scanning mode.

As a kind of underwater detecting technology, hyperspectral imaging technology has been well applied in many areas. But the systems usually have a large volume, and it is hard to mount them on different platforms because the external scanning mechanisms are needed for scanning imaging. To overcome these disadvantages, an underwater hyperspectral imaging system that achieves scanning imaging through moving the objective lens is designed. The design of the optical system and internal scanning and focusing structure were completed. According to the design result, the system is assembled and tested. The imaging quality of the whole system is good, and the obtained spectrum of different targets can be distinguished. The system has a good underwater detection capability, which can provide a new feasible technical scheme for underwater detection.

New Versatile Synthetic Route for the Preparation of Metal Phosphate Decorated Hydrogen Evolution Photocatalysts.

Photocatalytic hydrogen generation will benefit from the realization of more active but less expensive cocatalysts compared with noble metal counterparts. Herein we developed a universal vapor deposition method that selectively uses the thermal decomposition products of sodium hypophosphite as a phosphorus source for the fabrication of inexpensive and highly efficient metal phosphate (MPi) modified CdS nanorods. We find that the modification with a bimetal phosphate (i.e., 5 wt % NiCoPi) leads to an activity enhancement by a factor of approximately 52 in boosting visible-light-driven hydrogen evolution relative to the pristine CdS nanorods. The photocatalyst exhibits a high hydrogen generation rate of 13.44 mmol·g-1·h-1, which is much higher than that of its single metal counterparts (NiPi, 8.70 mmol·g-1·h-1; CoPi, 5.79 mmol·g-1·h-1) and 1 wt % Pt modified CdS (1.33 mmol·g-1·h-1). Its apparent quantum efficiency reaches 23.5% at 420 nm. Furthermore, it also shows remarkable photostability for eight consecutive cycles of photocatalytic activity tests with total reaction time of 24 h. The excellent photocatalytic performance of the photocatalyst is believed to be associated with the in situ formed NiICoP and NiCoIIIPi cocatalysts, which not only play an important role in photogenerated charge separation but also provide highly active catalytic reaction sites for the corresponding hydrogen evolution reaction and the sacrificial agent oxidation reaction.

Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP).

Glial fibrillary acidic protein (GFAP), an intracellular type III intermediate filament protein, provides structural support and maintains the mechanical integrity of astrocytes. It is predominantly found in the astrocytes which are the most abundant subtypes of glial cells in the brain and spinal cord. As a marker protein of astrocytes, GFAP may exert a variety of physiological effects in neurological diseases. For example, previous published literatures showed that autoimmune GFAP astrocytopathy is an inflammatory disease of the central nervous system (CNS). Moreover, the studies of GFAP in brain tumors mainly focus on the predictive value of tumor volume. Furthermore, using biomarkers in the early setting will lead to a simplified and standardized way to estimate the poor outcome in traumatic brain injury (TBI) and ischemic stroke. Recently, observational studies revealed that cerebrospinal fluid (CSF) GFAP, as a valuable potential diagnostic biomarker for neurosyphilis, had a sensitivity of 76.60% and specificity of 85.56%. The reason plasma GFAP could serve as a promising biomarker for diagnosis and prediction of Alzheimer's disease (AD) is that it effectively distinguished AD dementia from multiple neurodegenerative diseases and predicted the individual risk of AD progression. In addition, GFAP can be helpful in differentiating relapsing-remitting multiple sclerosis (RRMS) versus progressive MS (PMS). This review article aims to provide an overview of GFAP in the prediction of clinical progression in neuroinflammation, brain tumors, TBI, ischemic stroke, genetic disorders, neurodegeneration and other diseases in the CNS and to explore the potential therapeutic methods.

Eu(III) functionalized ZnMOF based efficient dual-emission sensor integrated with self-calibrating logic gate for intelligent detection of epinephrine.

The rapid detection of epinephrine (EPI) in serum holds immense importance in the early disease diagnosis and regular monitoring. On the basis of the coordination post-synthetic modification (PSM) strategy, a Eu3+ functionalized ZnMOF (Eu3+@ZnMOF) was fabricated by anchoring the Eu3+ ions within the microchannels of ZnMOF as secondary luminescent centers. Benefiting from two independent luminescent centers, the prepared Eu3+@ZnMOF shows great potential as a multi-signal self-calibrating luminescent sensor in visually and efficiently detecting serum EPI levels, with high reliability, fast response time, excellentrecycleability, and low detection limits of 17.8 ng/mL. Additionally, an intelligent sensing system was designed in accurately and reliably detecting serum EPI levels, based on the designed self-calibrating logic gates. Furthermore, the possible sensing mechanisms were elucidated through theoretical calculations as well as spectral overlaps. This work provides an effective and promising strategy for developing MOFs-based self-calibrating intelligent sensing platforms to detect bioactive molecules in bodily fluids.

Dapagliflozin attenuates myocardial hypertrophy via activating the SIRT1/HIF-1α signaling pathway.

As a sodium-glucose transporter 2 inhibitor (SGLT2i), the cardioprotective benefits of Dapagliflozin (DAPA) are now widely appreciated. However, the underlying mechanism of DAPA on angiotensin II (Ang II)-induced myocardial hypertrophy has never been evaluated. In this study, we not only investigated the effects of DAPA on Ang II-induced myocardial hypertrophy, but explored its underlying mechanisms. Mice were injected with Ang II (500 ng /kg/min) or saline solution as control, followed by intragastric administration DAPA (1.5 mg/kg/day) or saline for four weeks. DAPA treatment alleviated the condition of decrease in left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) caused by Ang II. In addition, DAPA treatment significantly alleviated Ang II-induced elevation of the ratio of heart weight to tibia length, as well as cardiac injury and hypertrophy. In mice stimulated with Ang II, the degree of myocardial fibrosis and upregulation of the markers of cardiac hypertrophy (atrial natriuretic peptide, ANP and B-type natriuretic peptide, BNP) were attenuated by DAPA. What's more, DAPA partially reversed the Ang II-induced upregulation of HIF-1α and the decrease in levels of SIRT1. Taken together, activating the SIRT1/HIF-1α signaling pathway was found to confer a protective effect against experimental myocardial hypertrophy in mice induced by Ang II, demonstrating its potential as an effective therapeutic target for pathological cardiac hypertrophy.

Detection of microplastics based on spatial heterodyne Raman spectroscopy.

As a new type of pollutant, microplastics have attracted extensive attention due to its characteristics such as small size and degradation difficulty under natural circumstance. Though there are many detection methods nowadays, there are still some limitations like long detection time, high false detection rate and expensive detection equipment, which make the detection of microplastics exists in natural environment hard to carry out. To improve the environmental conditions, rapid, efficient, and accurate detection methods for microplastics are needed urgently. In this paper, a method combined the Spatial heterodyne technology and Raman spectroscopy was proposed to detect the microplastics. A spatial heterodyne spectrometer (SHS) was built, and the algorithms used to process the spectrum data were introduced. An optical system used to collect the Raman signal of the sample was built and connected with the SHS. Four different kinds of microplastic samples were detected by the complete system and identification can be achieved according to the Raman spectrum. The samples were also detected by using a normal spectrometer for comparison. A comparison of Raman spectrum using conventional dispersion spectrometer was carried out and the result shows that SHS is of higher signal-to-noise ratio. The results indicate that SHRS technology has good performance and development prospects in the field of microplastics detection.

Minimization and optimization of α-amylase terminator for heterologous protein production in Bacillus licheniformis.

Terminators serve as the regulatory role in gene transcription termination; however, few researches about terminator optimization have been conducted, which leads to the lack of available and universal terminator for gene expression regulation in Bacillus. To solve this problem and expand synthetic biology toolbox of Bacillus licheniformis, the terminator T1 of endogenous α-amylase gene (amyL) was characterized in this research, with a termination efficiency of 87.81%. Then, we explored and optimized the termination strength of terminator T1 from four aspects: the distance between stop codon and terminator, GC content at the bottom of stem structure, loop size, and U-tract length, and the best terminator T24 was attained by combination optimization strategy, which termination efficiency was increased to 97.97%, better than the commonly used terminator T7 (T7P) from Escherichia coli. Finally, terminator T24 was applied to protein expression, which, respectively, led to 33.00%, 25.93%, and 11.78% increases of green fluorescence intensity, red fluorescence intensity, and keratinase activity, indicating its universality in protein expression. Taken together, this research not only expands a plug-and-play synthetic biology toolbox in B. licheniformis but also provides a reference for the artificial design of versatile intrinsic terminator.

Characterization of Desulfurized Crumb Rubber/Styrene-Butadiene-Styrene Composite Modified Asphalt Based on Rheological Properties.

With the growing interest in bituminous construction materials, desulfurized crumb rubber (CR)/styrene-butadiene-styrene (SBS) modified asphalts have been investigated by many researchers as low-cost environmental-friendly road construction materials. This study aimed to investigate the rheological properties of desulfurized CR/SBS composite modified asphalt within various temperature ranges. Bending beam rheometer (BBR), linear amplitude sweep (LAS), and multiple stress creep recovery (MSCR) tests were performed on conventional CR/SBS composite modified asphalt and five types of desulfurized CR/SBS modified asphalts. Meanwhile, Burgers' model and the Kelvin-Voigt model were used to derive nonlinear viscoelastic parameters and analyze the viscoelastic mechanical behavior of the asphalts. The experimental results indicate that both the desulfurized CR/SBS composite modifier and force chemical reactor technique can enhance the crosslinking of CR and SBS copolymer, resulting in an improved high-, intermediate-, and low-temperature performance of desulfurized CR/SBS composite modified asphalt. Burgers' model was found to be apposite in simulating the creep stages obtained from MSCR tests for CR/SBS composite modified asphalts. The superior high-temperature performance of desulfurized CR/SBS modified asphalt prepared with 4% SBS, 20% desulfurized rubber, and a force chemical reactor time of 45 min contributes to the good high-temperature elastic properties of the asphalt. Therefore, this combination is recommended as an optimal preparation process. In summary, the desulfurization of crumb rubber and using the force chemical reactor technique are beneficial to composite asphalt performance and can provide a new way of utilizing waste tire rubber.

Study on Storage Stability of Activated Reclaimed Rubber Powder Modified Asphalt.

The purpose of this research was to make full use of waste lubricating by-products (LBP) and reclaimed rubber powder (RR) to modify asphalt by a one-pot approach, so as to achieve the dual purpose of solving the poor storage stability of reclaimed rubber powder modified asphalt (RRMA) and the realization of solid waste recycling. A variety of characterization techniques were performed to analyze storage stability, conventional properties and microstructure of LBP-activated reclaimed rubber powder modified asphalt (Blend). Fourier transform infrared spectroscopy illustrated that not only the chemical composition of LBP was very similar to that of asphalt, but also the activation of LBP improved the compatibility of RR with asphalt and enhanced the storage stability of Blend. Fluorescence spectrum and scanning electron microscopy results indicated that the RR without LBP activation was aggregated and dispersed as blocks in asphalt, while the LBP activated RR was uniformly dispersed in the asphalt phase. The segregation test demonstrated that Blend exhibited outstanding storage stability, in which the softening point difference was within 2.5 °C and the segregation rate was -0.2-0.2. In addition, the conventional properties of Blend have been significantly improved, especially in penetration and ductility. More importantly, the short-term aging results demonstrated that, compared with RRMA, Blend possessed excellent anti-aging performance.

Rheological and Aging Properties of Composite Modified Bitumen by Styrene-Butadiene-Styrene and Desulfurized Crumb Rubber.

Taking advantage of crumb rubber from waste tires to modify bitumen is widely for the environmentally friendly and sustainable development of pavement. This study investigated the modification mechanism, rheological, and aging properties of styrene-butadiene-styrene (SBS)/desulfurized crumb rubber (DCR) composite modified bitumen (SBS/DCRMB). Morphological features and chemical characteristics were assessed by fluorescence intensity measurement and gel permeation chromatography (GPC), respectively, and results demonstrated that the DCR and SBS modifier in SBS/DCRMB had been vulcanized and formed a three-dimensional network structure. Moreover, a comparison of the GPC elution curve showed the residual bitumen hardly changed due to carbon black released from DCR of SBS/DCRMB during the aging process of SBS/DCRMB, and the polymer molecules condensed to larger units. However, the remaining bitumen in SBSMB had changed evidently and the polymer degraded to smaller molecules. Meanwhile the rheological testing results, including multiple stress creep recovery, linear amplitude sweep and bending beam rheometer, declared that the SBS/DCRMB is superior to SBSMB before and after aging.