An aberration-free line scan confocal Raman imager and type classification and distribution detection of microplastics.

An aberration-free line scanning confocal Raman imager (named AFLSCRI) is developed to achieve rapid Raman imaging. As an application example, various types and sizes of MPs are identified through Raman imaging combined with a machine learning algorithm. The system has excellent performance with a spatial resolution of 2 µm and spectral resolution of 4 cm-1. Compared to traditional point-scanning Raman imaging systems, the detection speed is improved by 2 orders of magnitude. The pervasive nature of MPs results in their infiltration into the food chain, raising concerns for human health due to the potential for chemical leaching and the introduction of persistent organic pollutants. We conducted a series of experiments on various types and sizes of MPs. The system can give a classification accuracy of 98% for seven different types of plastics, and Raman imaging and species identification for MPs as small as 1 µm in diameter were achieved. We also identified toxic and harmful substances remaining in plastics, such as Dioctyl Phthalate (DOP) residues. This demonstrates a strong performance in microplastic species identification, size recognition and identification of hazardous substance contamination in microplastics.

Label-free analysis of the ß-hydroxybutyricacid drug on mitochondrial redox states repairment in type 2 diabetic mice by resonance raman scattering.

BACKGROUND: Mitochondrial redox imbalance underlies the pathophysiology of type2 diabetes mellitus (T2DM), and is closely related to tissue damage and dysfunction. Studies have shown the beneficial effects of dietary strategies that elevate ß-hydroxybutyrate (BHB) levels in alleviating T2DM. Nevertheless, the role of BHB has not been clearly elucidated. METHODS: We performed a spectral study to visualize the preventive effects of BHB on blood and multiorgan mitochondrial redox imbalance in T2DM mice via using label-free resonance Raman spectroscopy (RRS), and further explored the impact of BHB therapy on the pathology of T2DM mice by histological and biochemical analyses. FINDINGS: Our data revealed that RRS-based mitochondrial redox states assay enabled clear and reliable identification of the improvement of mitochondrial redox imbalance by BHB, evidenced by the reduction of Raman peak intensity at 750 cm-1, 1128 cm-1 and 1585 cm-1 in blood, tissue as well as purified mitochondria of db/db mice and the increase of tissue mitochondrial succinic dehydrogenase (SDH) staining after BHB treatment. Exogenous supplementation of BHB was also found to attenuate T2DM pathology related to mitochondrial redox states, involving organ injury, blood glucose control, insulin resistance and systemic inflammation. INTERPRETATION: Our findings provide strong evidence for BHB as a potential therapeutic strategy targeting mitochondria for T2DM.

MMCT-Loop: a mix model-based pipeline for calling targeted 3D chromatin loops.

Protein-specific Chromatin Conformation Capture (3C)-based technologies have become essential for identifying distal genomic interactions with critical roles in gene regulation. The standard techniques include Chromatin Interaction Analysis by Paired-End Tag (ChIA-PET), in situ Hi-C followed by chromatin immunoprecipitation (HiChIP) also known as PLAC-seq. To identify chromatin interactions from these data, a variety of computational methods have emerged. Although these state-of-art methods address many issues with loop calling, only few methods can fit different data types simultaneously, and the accuracy as well as the efficiency these approaches remains limited. Here we have generated a pipeline, MMCT-Loop, which ensures the accurate identification of strong loops as well as dynamic or weak loops through a mixed model. MMCT-Loop outperforms existing methods in accuracy, and the detected loops show higher activation functionality. To highlight the utility of MMCT-Loop, we applied it to conformational data derived from neural stem cell (NSCs) and uncovered several previously unidentified regulatory regions for key master regulators of stem cell identity. MMCT-Loop is an accurate and efficient loop caller for targeted conformation capture data, which supports raw data or pre-processed valid pairs as input, the output interactions are formatted and easily uploaded to a genome browser for visualization.

A low-temperature digital microfluidic system used for protein-protein interaction detection.

The occurrence, development and prediction of various biological processes and diseases are inseparable from the protein-protein interaction (PPI), so it is extremely meaningful to perfect PPI networks. However, shortcomings of traditional detection methods, such as protein degradation, long detection time, complex operation, poor automation and high cost, restrict the rapid development of PPI networks. Here, a low-temperature digital microfluidic (LTDMF) system-based PPI detection box (LTDMF-PPI-Box) was developed to achieve rapid, lossless and efficient PPI detection. It consists of a PMMA shell, LTDMF-PPI and an integrated temperature control system. LTDMF reduces the PPI detection time from tens of hours to 1.5 hours by programmatically controlling the movement of droplets. Moreover, an integrated thermoelectric cooler (TEC) ensures an operating temperature of 4 °C, resulting in a protein protection up to 90%. The interaction between RILP protein and Rab26 protein which has a close connection to insulin secretion was demonstrated as a prototype to illustrate the feasibility of the LTDMF-PPI-Box. LTDMF with automation characteristics is capable of meeting the requirement of high-throughput screening of interacting proteins; therefore, the LTDMF-PPI-Box is expected to accelerate the establishment of the PPI network in the future.

A capillary-based microfluidic chip with the merits of low cost and easy fabrication for the rapid detection of acute myocardial infarction.

Point-of-care testing methods currently utilize rapid, portable, inexpensive, and multiplexed on-site detection. Microfluidic chips have become a very promising platform with broad development prospects due to their breakthrough improvement in miniaturization and integration. However, the conventional microfluidic chips still have disadvantages, such as difficulty in fabrication processing, long production time and high cost, which hinder its applications in the fields of POCT and in vitro diagnostics. In this study, a capillary-based microfluidic chip with the characteristics of low cost and easy fabrication was developed for the rapid detection of acute myocardial infarction (AMI). Several short capillaries, which were already conjugated with the capture antibodies respectively, were connected by peristaltic pump tubes and then formed the working capillary. Two working capillaries were encapsulated in the plastic shell and ready for the immunoassay. Multiplex detection of Myoglobin (Myo), cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were chosen to demonstrate the feasibility and analytical performance of the microfluidic chip, which requires rapid and accurate detection during diagnosis and therapy for AMI. The capillary-based microfluidic chip required tens of minutes to prepared, and its cost was less than $1. The limit of detection (LOD) was 0.5 ng/mL for Myo, 0.1 ng/mL for cTnI and 0.5 ng/mL for CK-MB respectively. The capillary-based microfluidic chips with easy fabrication and low cost hold promise for the portable and low-cost detection of target biomarkers.

Molecular mechanism of XB130 adaptor protein mediates trastuzumab resistance in gastric cancer.

BACKGROUND: Recent studies have shown that the activation of PI3K/AKT signaling pathway is an essential molecular mechanism participating in trastuzumab resistance in HER2 + GC (gastric cancer). However, how can we effectively inhibit AKT activity associated with drug resistance during trastuzumab treatment? Screening inhibitors against the upstream receptors of PI3K/AKT signaling pathway or interacting proteins of members has become an important way. METHODS: In this study, western blot, qRT-PCR, CCK8, Co-IP and other techniques were used to explore possible mechanisms participating in trastuzumab resistance in vitro. Besides, the xenograft mouse model and GC tissue samples from patients were used to further validate the in-vitro results. RESULTS: The expression of XB130 adaptor protein was remarkably increased in GC cell lines resistant to trastuzumab, and knockdown of XB130 could reverse the resistance via downregulating p-AKT. In addition, p-SRC (Tyr416) was increased in resistant cells, which could facilitate the binding of XB130 to PI3K p85α. It was also discovered that XB130 could negatively regulate PTEN gene transcription, and thus a positive feedback loop was formed between SRC-XB130-PTEN. CONCLUSIONS: In HER2 + GC, XB130 contributes to trastuzumab resistance by stimulating the PI3K/AKT signaling pathway through binding to PI3K p85α under the mediation of SRC kinase and regulating PTEN gene transcription, and in turn forming a positive feedback loop between SRC-XB130-PTEN.

Detecting the research trends and evolution of energy resilience: a bibliometric analysis.

The concept of resilience is widely used in many specific fields, such as energy. Energy resilience is receiving increasing scientific attention. In the long-term sustainable development of society, energy and resilience policies are the key strategies to achieve international development goals. This paper analyzes the existing energy resilience literature and presents the research hot spots and trends. After extracting 4887 articles from the Science Citation Index Expanded and Social Sciences Citation Index databases, this paper takes the literature data during 1985-2021 through topic search using the keywords of energy resilience and applies bibliometrics to study the development traits of the field. The primary research purposes are to discover the knowledge framework of energy resilience, together with a review of integral development trends, elementary publication characteristics, and an analysis of related leading journals. Aside from analyzing the number of publications, citations, and cooperation types, this study identifies the most prolific researchers from the country-level, institution-level, and author-level in this area, thus providing a longitudinal overview of the dynamic research evolution of energy resilience and the knowledge spread locus in this domain.

4D dual-mode staring hyperspectral-depth imager for simultaneous spectral sensing and surface shape measurement.

A 4D dual-mode staring hyperspectral-depth imager (DSHI), which acquire reflectance spectra, fluorescence spectra, and 3D structural information by combining a staring hyperspectral scanner and a binocular line laser stereo vision system, is introduced. A 405 nm laser line generated by a focal laser line generation module is used for both fluorescence excitation and binocular stereo matching of the irradiated line region. Under the configuration, the two kinds of hyperspectral data collected by the hyperspectral scanner can be merged into the corresponding points in the 3D model, forming a dual-mode 4D model. The DSHI shows excellent performance with spectral resolution of 3 nm, depth accuracy of 26.2 µm. Sample experiments on a fluorescent figurine, real and plastic sunflowers and a clam are presented to demonstrate system's with potential within a broad range of applications such as, e.g., digital documentation, plant phenotyping, and biological analysis.

MultiscaleDTA: A multiscale-based method with a self-attention mechanism for drug-target binding affinity prediction.

The task of predicting drug-target affinity (DTA) plays an increasingly important role in the early stage of in silico drug discovery and development. Currently, a variety of machine learning-based methods have been presented for DTA prediction and achieved outstanding performance, which is beneficial for speeding up the development of new drugs. However, most convolutional neural networks (CNNs) based methods ignore the significance of information from CNN layers with different scales for DTA prediction. In addition, each feature provides different contributions to the final task. Therefore, in this study, we propose a novel end-to-end deep learning-based framework, MultiscaleDTA, to predict drug-target binding affinity. MultiscaleDTA incorporates multi-scale CNNs and a self-attention mechanism to capture multi-scale and comprehensive features for characterizing the intrinsic properties of drugs and targets. Extensive experimental results on both regression and binary classification tasks demonstrate that MultiscaleDTA achieves competitive performance compared to state-of-the-art methods.

MiR-623 links lncRNA RP11-89 and cyclin D1 to regulate the proliferation of glioblastoma cells.

PURPOSE: The tumorigenesis of bladder cancer has been proven to be related to the increased expression of lncRNA RP11-89, the participation of which in glioblastoma (GBM) is unknown. We predicted that RP11-89 could be targeted by miR-623, which targets cyclin D1. We then analyzed the role of RP11-89 in GBM. MATERIALS AND METHODS: Samples of both GBM and paired non-tumor tissue were obtained from 58 GBM patients to analyze the expression of RP11-89 and miR-623 through RT-qPCR. The direct binding of miR-623 to RP11-89 was analyzed with RNA-RNA pull down. The role of RP11-89 and miR-623 in regulating each other's expression was analyzed with overexpression assay. The role of RP11-89 and miR-623 in regulating the expression of cyclin D1 and GBM cell proliferation was analyzed by Western blot and BrdU assay, respectively. RESULTS: RP11-89 was expressed in high amounts in GBM, while miR-623 was expressed in low amounts in GBM. RP11-89 and miR-623 were not closely correlated, while miR-623 directly bound to RP11-89. RP11-89 and miR-623 showed no direct role in each other's expression. RP11-89 suppressed the role of miR-623 in downregulating cyclin D1 and GBM cell proliferation. CONCLUSIONS: Therefore, miR-623 may link lncRNA RP11-89 and cyclin D1 to regulate the proliferation of GBM cells.

GSAML-DTA: An interpretable drug-target binding affinity prediction model based on graph neural networks with self-attention mechanism and mutual information.

Identifying drug-target affinity (DTA) has great practical importance in the process of designing efficacious drugs for known diseases. Recently, numerous deep learning-based computational methods have been developed to predict drug-target affinity and achieved impressive performance. However, most of them construct the molecule (drug or target) encoder without considering the weights of features of each node (atom or residue). Besides, they generally combine drug and target representations directly, which may contain irrelevant-task information. In this study, we develop GSAML-DTA, an interpretable deep learning framework for DTA prediction. GSAML-DTA integrates a self-attention mechanism and graph neural networks (GNNs) to build representations of drugs and target proteins from the structural information. In addition, mutual information is introduced to filter out redundant information and retain relevant information in the combined representations of drugs and targets. Extensive experimental results demonstrate that GSAML-DTA outperforms state-of-the-art methods for DTA prediction on two benchmark datasets. Furthermore, GSAML-DTA has the interpretation ability to analyze binding atoms and residues, which may be conducive to chemical biology studies from data. Overall, GSAML-DTA can serve as a powerful and interpretable tool suitable for DTA modelling.

miR-301a-3p induced by endoplasmic reticulum stress mediates the occurrence and transmission of trastuzumab resistance in HER2-positive gastric cancer.

Trastuzumab resistance negatively influences the clinical efficacy of the therapy for human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC), and the underlying mechanisms remain elusive. Exploring the mechanisms and finding effective approaches to address trastuzumab resistance are of great necessity. Here, we confirmed that endoplasmic reticulum (ER) stress-induced trastuzumab resistance by up-regulating miR-301a-3p in HER2-positive GC cells. Moreover, we elucidated that miR-301a-3p mediated trastuzumab resistance by down-regulating the expression of leucine-rich repeats and immunoglobulin-like domains containing protein 1 (LRIG1) and subsequently activating the expression of insulin-like growth factor 1 receptor (IGF-1R) and fibroblast growth factor receptor 1 (FGFR1) under ER stress. We also found that intercellular transfer of miR-301a-3p by exosomes disseminated trastuzumab resistance. The present study demonstrated that exosomal miR-301a-3p could serve as a non-invasive biomarker for trastuzumab resistance, which was maybe a novel potential therapeutic target to overcome trastuzumab resistance and improve the curative effect of trastuzumab in HER2-positive GC patients.

Study on degradation of diesel pollutants in seawater by composite photocatalyst MnO2/ZrO2.

In this paper, the effectiveness of the composite photocatalyst was studied by using manganese dioxide (MnO2)/zirconium dioxide (ZrO2) to degrade diesel pollutants in seawater under visible light.The MnO2/ZrO2 photocatalyst was prepared by co-precipitation and characterized by scanning electron microscopy, X-ray powder diffraction, energy-dispersive spectroscopy and UV-Vis diffuse reflectance spectroscopy analysis. This is the first report on a comprehensive analytical study on the effect of various physio-chemical parameters on diesel degradation using the synthesized MnO2/ZrO2 photocatalysts. The effects of doping ratio of MnO2/ZrO2, dosage, initial diesel concentration, calcination temperature, concentration of H2O2 solutions and illumination time on the diesel degradation were investigated. The degradation of diesel pollution in seawater was optimized by orthogonal experiment. According to the results, the prepared samples were monoclinic form and the MnO2 was successfully doped into the bulk ZrO2. The absorption edge of the MnO2/ZrO2 photocatalysts exhibited red shift, and this red shifts imply enhanced photon absorption under visible light compared with the pure ZrO2. The results showed that under optimum reaction conditions, the degradation rate can reach 92.92%. The result of this study will enable ZrO2 to make more effective use of sunlight and improve the actual value of photocatalytic technology in the field of contaminant treatment.

Application of Fe2O3/ZrO2 loaded polyhedron ball on photocatalytic degradation of diesel pollutants in seawater under visible light.

Fe2O3/ZrO2 nanocomposite photocatalyst was successfully prepared by coprecipitation method for the degradation of diesel pollutants in seawater under visible light. The effects of doping ratio, calcination temperature, photocatalyst dosage, initial diesel concentration, H2O2 concentration, and reaction time on the photocatalytic removal efficiency were investigated. Moreover, the optimal conditions for Fe2O3/ZrO2 nanocomposite photocatalyst to degrade marine diesel pollution were determined. The removal efficiency of diesel by nanocomposite photocatalyst could reach 97.03%. A photocatalyst-loaded polypropylene polyhedral ball was prepared, and the removal efficiency of diesel by photocatalyst-loaded polypropylene polyhedral ball decreased from 99.35 to 68.84% after four recycling cycles.

Photocatalytic degradation of marine diesel oil spills using composite CuO/ZrO2 under visible light.

Diesel oil spills in marine environments pose a severe threat to both aquatic and terrestrial ecosystems. Photocatalysis is an environment-friendly method for marine oil remediation; however, its practical usage is limited due to several issues. In this study, we demonstrate the enhanced efficacy of doped CuO/ZrO2 photocatalyst at degrading marine diesel in comparison to undoped ZrO2. The photocatalysts were prepared using co-precipitation method, and their physical and chemical properties were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and ultraviolet-visible spectroscopy (UV-Vis). XRD analysis showed that the photocatalytic crystallite size of ZrO2 and CuO/ZrO2 was 28.80 nm and 40.32 nm, respectively. Both catalysts exhibited stable crystalline forms. UV-Vis analysis showed that doping of ZrO2 with CuO significantly reduced its band gap from 4.61 eV to 1.18 eV, thus enhancing the utilization of visible light. The effect of catalyst dosage, doping ratio, and initial diesel concentration on the degradation rate of diesel was investigated by performing single-factor experiments. The optimization experiment results showed that 96.96% of diesel could be degraded under visible light. This study laid an experimental foundation for expanding the practical applications of photocatalytic technology.

Adsorption of chlortetracycline from aquaculture wastewater using modified zeolites.

In this study, lanthanum modified zeolite (La-Z) was used to adsorb chlortetracycline (CTC) from aquaculture wastewater. La-Z was characterized by SEM, TEM, EDS, XRD, FTIR and BET. The effects various factors on the adsorption of CTC by La-Z were investigated, including the lanthanum modification concentration on zeolites, the dosage of La-Z, solution pH and reaction time. Orthogonal experiments were performed to determine the optimal adsorption conditions. Adsorption kinetics were studied by quasi-first-order model, quasi-second-order model, Weber-Morris, Boyd and Bangham models, while isotherms were analyzed by the Langmuir and Freundlich models. The removal rate reached 98.4%, when the modified concentration was 0.02 mol/L, the adsorbent dosage was 0.04 g, the initial concentration of CTC was 5 mg/L, the adsorption time was 20 min, and the pH was 7. The initial CTC concentration had the greatest influence on the adsorption process. The kinetic results showed a significant linear correlation between the experimental results and the quasi-second-order kinetic model. From the results of the internal diffusion model, it was found that the La-Z adsorption rate was controlled by both internal diffusion and external diffusion, in a multi-step process. The adsorption isotherm conforms to the Langmuir model, with the maximum adsorption quantity reaching 127.55 mg/g. Thermodynamic analysis showed that the adsorption process was an endothermic process of entropy increase, which occurs spontaneously.

Autofluorescence-Free Immunoassay Using X-ray Scintillating Nanotags.

Autofluorescence background in complex biological samples is a major challenge in achieving high sensitivity of fluorescence immunoassays (FIA). Here we report an X-ray luminescence-based immunoassay for high-sensitivity detection of biomarkers using X-ray scintillating nanotags. Due to the weak scattering and absorption of most biological chromophores by X-ray excitation, a low-dose X-ray source can be used to produce intense scintillating luminescence from the nanotags for autofluorescence-free biosensing. To demonstrate this concept, we designed and synthesized NaGdF4:Tb@NaYF4 core/shell nanoparticles as kind of high-efficiency X-ray scintillating nanotags, which are able to convert high-energy X-ray photons to visible light without autofluorescence in biological samples. Notably, strong X-ray absorption and minimized surface quenching arising from the heavy Gd3+/Tb3+ atoms and core/shell architecture of the nanoparticles were found to be critically important for high-efficiency X-ray excited luminescence for high-sensitivity biosensing. Our method allows for sensing alpha-fetoprotein (AFP) biomarkers with a detection limit down to 0.25 ng/mL. Moreover, the as-described X-ray luminescence immunoassay exhibited an excellent biological specificity, high stability, and sample recovery, implying an opportunity for applications in complex biological samples. Consequently, our method can be readily extended for multiplexing sensing and medical diagnosis.

Expression of Connexin43 in Cerebral Arteries of Patients with Moyamoya Disease.

BACKGROUND AND PURPOSE: Moyamoya disease has a high incidence of cerebral vascular accident in children and adolescents, which can endanger the physical and mental health of children and adults seriously. However, the etiology and the pathogenesis of moyamoya disease remain unclear. Connexin43 (Cx43) is a predominant intercellular gap junction protein that plays an important role in the normal function of arteries and the development of several cardiovascular diseases. We aimed to preliminarily investigate pathological changes and the expression of Cx43 in cerebral arteries of patients with moyamoya disease. MATERIALS AND METHODS: This study collected 10 experimental cerebral artery specimens from patients with moyamoya disease and 10 control cerebral artery specimens from patients without moyamoya disease during surgery, then pathological changes and change in Cx43 expression of cerebral artery specimens were investigated in the 2 groups by hematoxylin and eosin staining and immunofluorescence. RESULTS: The intima of cerebral arteries was thin with monolayer endothelial cells in the control group but had asymmetrical thickening for the cerebral arteries in the experimental group. The mean ± standard deviation of the mean optical density of Cx43 in the experimental group was .065 ± .011 (range, .045-.081), whereas that in the control group was .035 ± .005 (range, .028-.042). The expression of Cx43 in the experimental group was statistically significantly higher in comparison with the control group (P < .01). CONCLUSION: The abnormal expression of Cx43 in the cerebral arteries may play an important role in the formation of vascular intima thickening in patients with moyamoya disease.