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Summary: Background: This study explores the potential of the deep learning-based convolutional neural network (CNN) to automatically recognize MMD using MRA images from atherosclerotic disease (ASD) and normal control (NC). Methods: In this retrospective study in China, 600 participants (200 MMD, 200 ASD and 200 NC) were collected from one institution as an internal dataset for training and 60 from another institution were collected as external testing set for validation. All participants were divided into training (N = 450) and validation sets (N = 90), internal testing set (N = 60), and external testing set (N = 60). The input to the CNN models comprised preprocessed MRA images, while the output was a tripartite classification label that identified the patient's diagnostic group. The performances of 3D CNN models were evaluated using a comprehensive set of metrics such as area under the curve (AUC) and accuracy. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to visualize the CNN's decision-making process in MMD diagnosis by highlighting key areas. Finally, the diagnostic performances of the CNN models were compared with those of two experienced radiologists. Findings: DenseNet-121 exhibited superior discrimination capabilities, achieving a macro-average AUC of 0.977 (95% CI, 0.928–0.995) in the internal test sets and 0.880 (95% CI, 0.786–0.937) in the external validation sets, thus exhibiting comparable diagnostic capabilities to those of human radiologists. In the binary classification where ASD and NC were group together, with MMD as the separate group for targeted detection, DenseNet-121 achieved an accuracy of 0.967 (95% CI, 0.886–0.991). Additionally, the Grad-CAM results for the MMD, with areas of intense redness indicating critical areas identified by the model, reflected decision-making similar to human experts. Interpretation: This study highlights the efficacy of CNN model in the automated diagnosis of MMD on MRA images, easing the workload on radiologists and promising integration into clinical workflows. Funding: National Natural Science Foundation of China, Tianjin Science and Technology Project and Beijing Natural Science Foundation.

Abstract Stipes are the major waste from the processing of Lentinus edodes. To make full use of L. edodes stipes (LES), different fractions of LES polysaccharides (LESPs) were first obtained by water extraction and gradient ethanol precipitation. Afterwards, the LES residues were treated with an optimal combination of Aspergillus niger and Saccharomyces cerevisiae for the preparation of soluble/insoluble dietary fibers (LESS/LESI) using the response surface methodology and the Box-Behnken design. Subsequently, the in vitro immunomodulatory activity of LESPs and LESS, as well as the adsorption capacities of LESI were evaluated. The results showed that LESPs were neutral polysaccharides, mainly containing glucose. The optimal parameters for modifying the residues of LES were the followings: 4% (w/w) A. niger, 8% (w/w) S. cerevisiae, 31 ℃, 3 d, and a solid–liquid ratio of 1:12.5 in a yield of 14.73%/82.45% of LESS/LESI, respectively. The in vitro immunomodulatory activity assays revealed that LESPs and LESS had potent immunostimulatory activity to increase phagocytosis, acid phosphatase activity and nitric oxide production of RAW264.7 murine cell macrophages. The evaluation of adsorption capacities revealed that LESI owned stronger water holding capacity, oil holding capacity and water swelling capacity. This research could provide an effective way to fully utilize discarded L. edodes stipes with high added-value. Graphical Abstract An effective strategy was built to fully utilize discarded L. edodes stipes by preparing polysaccharides (LESPs-20, LESPs-50 and LESPs-80), soluble and insoluble dietary fibers (LESS/LESI). Their products showed immunomodulatory activity and adsorption capacities.

Carbon materials have excellent catalytic effects on the hydrogen storage performance of MgH2. Here, carbon-supported Ni3S2 (denoted as Ni3S2@C) was synthesized by a facile chemical route using ion exchange resin and nickel acetate tetrahydrate as raw materials and then introduced to improve the hydrogen storage properties of MgH2. The results indicated the addition of 10 wt.% Ni3S2@C prepared by macroporous ion exchange resin can effectively improve the hydrogenation/dehydrogenation kinetic properties of MgH2. At 100 °C, the dehydrogenated MgH2-Ni3S2@C-4 composite could absorb 5.68 wt.% H2. Additionally, the rehydrogenated MgH2-Ni3S2@C-4 sample could release 6.35 wt.% H2 at 275 °C. The dehydrogenation/hydrogenation enthalpy changes of MgH2-Ni3S2@C-4 were calculated to be 78.5 kJ mol−1/−74.7 kJ mol−1, i.e., 11.0 kJ mol−1/7.3 kJ mol−1 lower than those of MgH2. The improvement in the kinetic properties of MgH2 was ascribed to the multi-phase catalytic action of C, Mg2Ni, and MgS, which were formed by the reaction between Ni3S2 contained in the Ni3S2@C catalyst and Mg during the first hydrogen absorption–desorption process.

IntroductionStaphylococcus aureus infection has long been a serious concern in the medical field, with methicillin-resistant Staphylococcus aureus (MRSA) posing a considerable challenge to public health. Given the escalating bacterial resistance and the favorable biosafety and environmental properties of phages, the resurgence of phage therapy offers a promising alternative to antibiotics.MethodsIn this study, we isolated and characterized a MRSA phage named StAP1 from a Chinese hospital. Phenotypic and molecular analyses revealed its broad-spectrum characteristics, genomic background, and potential application in MRSA infection treatment.ResultsMorphological examination classified the phage as a member of the Herelleviridae phage family, displaying a typical hexagonal head and a slender fibrous tail. Genomic analysis unveiled a size of ~144,705 bp for the StAP1 genome, encompassing 215 open reading frames (ORFs). The one-step growth curve demonstrated a 20-min incubation period for the phage, with an optimal multiplicity of infection (MOI) of 0.1. Moreover, StAP1 exhibited stability across a wide range of temperatures and pH levels. Further investigation of its broad-spectrum characteristics confirmed its ability to effectively infect all staphylococcal cassette chromosomal mec (SCCmec) types found in MRSA strains, notably displaying a remarkable lysis rate of 76.7% against the prevalent ST239 strain in China. In vivo studies show cased significant efficacy of the StAP1 phage against MRSA infection.DiscussionOverall, StAP1 phage presents a broad infection spectrum and exhibits strong lytic effects on various MRSA strains, highlighting its tremendous potential as a powerful tool for MRSA infection treatment.

Aiming at the issue of parameter matching in conventional two-step location, a reduced dimension multiple signal classification direct position determination algorithm based on multi-array is proposed. Based on the idea of dimension reduction, the algorithm avoids multi-dimensional search in spatial domain and attenuation coefficient domain and reduces the search complexity. Simulation results show that the performance of the algorithm is better than the traditional angle of arrival two-step localization algorithm and subspace data fusion direct localization algorithm.

Brucellosis is a globally zoonotic bacterial disease of humans and various animals including goats, sheep, and cattle. Brucella melitensis M5-90, a live attenuated vaccine strain, has been widely used to prevent brucellosis in goats and sheep. However, the molecular mechanisms governing protective immunity response in non-professional phagocytes infected with B. melitensis M5-90 have not been fully investigated, especially in goats. In our research, goat fibroblasts were used as in vitro models to determine these mechanisms by transcriptome analysis. After incubating with B. melitensis M5-90 3 h, the infected goat fibroblasts were collected at 0 h, 4 h, 24 h, 48 h and 72 h for RNA-seq. The results indicated that there were totally 11,819 differentially expressed genes (DEGs) and 777 differentially expressed (DE) miRNAs found in experiment groups compared with the control groups (|log2(Foldchange)|≥1, FDR

Delta bovine papillomaviruses (δBPVs) mainly infect cattle and cause fibropapillomas. δBPVs encode three oncogenes, E5, E6 and E7. The effect of E6 on microRNA (miRNA) and mRNA expression profiles is not well characterized. In this study, RNA sequencing and small RNA sequencing were used to explore alterations in mRNAs and miRNAs in E6 over-expressing NIH/3T3 cells (NH-E6) compared with control cells (NH-GFP). We found that 350 genes (181 upregulated and 169 downregulated) and 54 miRNAs (26 upregulated and 28 downregulated) were differentially expressed (DE) following E6 expression. The top 20 significantly enriched GO terms in “biological process” included inflammatory response, innate immune response, immune response, immune system process, positive regulation of apoptotic process, cell adhesion, and angiogenesis. We constructed a potential miRNA-gene regulatory network from the differentially expressed genes (DEGs) and DE miRNAs. Finally, we selected 19 immune-response related DEGs and 11 DE miRNAs for qPCR validation. Of these, upregulation of 12 genes, Ccl2, Ccl7, Cxcl1, Cxcl5, Tlr2, Nfkbia, Fas, Il1rl1, Ltbp1, Rab32, and Zc3h12a, Dclk1 and downregulation of four genes, Agtr2, Ptx3, Sfrp1, and Thbs1 were confirmed. Ccl2, Ccl7, Cxcl1 and Cxcl5 were upregulated more than ten-fold in NH-E6 compared with NH-GFP. Also, upregulation of three miRNAs, mmu-miR-129-2-3p, mmu-miR-149-5p-R-2 and mmu-miR-222-3p, and downregulation of five miRNAs, mmu-miR-582-3p-R+1, mmu-miR-582-5p, mmu-miR-708-3p, mmu-miR-708-5p and mmu-miR-1197-3p, were confirmed. Our study describes changes in both mRNA and miRNA profiles in response to BPV E6 expression, providing new insights into BPV E6 oncogene functions.

Orf, caused by Orf virus (ORFV), is a globally distributed zoonotic disease responsible for serious economic losses in the agricultural sector. However, the mechanism underlying ORFV infection remains largely unknown. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, play important roles in various pathological processes but their involvement in ORFV infection and host response is unclear. In the current study, whole transcriptome sequencing and small RNA sequencing were performed in ORFV-infected goat skin fibroblast cells and uninfected cells. A total of 151 circRNAs, 341 messenger RNAs (mRNAs), and 56 microRNAs (miRNAs) were differently expressed following ORFV infection. Four circRNAs: circRNA1001, circRNA1684, circRNA3127 and circRNA7880 were validated by qRT-PCR and Sanger sequencing. Gene ontology (GO) analysis indicated that host genes of differently expressed circRNAs were significantly enriched in regulation of inflammatory response, epithelial structure maintenance, positive regulation of cell migration, positive regulation of ubiquitin-protein transferase activity, regulation of ion transmembrane transport, etc. The constructed circRNA-miRNA-mRNA network suggested that circRNAs may function as miRNA sponges indirectly regulating gene expression following ORFV infection. Our study presented the first comprehensive profiles of circRNAs in response to ORFV infection, thus providing new clues for the mechanisms of interactions between ORFV and the host.

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) are a crucial component of the tumor microenvironment (TME), with hypoxic conditions promoting their migration to tumors. Exosomes play a vital role in cell-to-cell communication within the TME. Hypoxic TME have a great impact on the release, uptake and biofunctions of exosomes. This study aims to elucidate the communication between BMSC-derived exosomal miRNA and triple-negative breast cancer (TNBC) in a hypoxic environment. Methods Exosomes were isolated via ultracentrifugation and identified using scanning electron microscopy (SEM), nanoparticle tracking analysis (NTA) and western blot. A range of bioinformatics approaches were used to screen exosomal miRNAs and the target mRNAs of miRNAs and predict the possible signaling pathways. Expression levels of genes and proteins were assessed by quantitative real-time PCR and western blot. Cell proliferation, apoptosis, migration and invasion were analyzed using CCK-8 assay, EDU assay, transwell migration, wound healing assay and invasion assay, respectively. Dual luciferase reporter gene assay was conducted to confirm the binding between miRNAs and the target mRNAs. The impact of hypoxic BMSC-derived exosomal miRNA on TNBC progression in vivo was evaluated using tumor xenograft nude mouse models. Furthermore, the impact of patients’ serum exosomal miRNA on TNBC was implemented. Results Exosomes derived from hypoxic BMSCs promotes the proliferation, migration, invasion and epithelial-mesenchymal transition of TNBC and suppresses the apoptosis of TNBC. The expression of miR-210-3p in BMSC-derived exosomes is markedly elevated in hypoxic conditions. Exosome-mediated transfer of miR-210-3p from hypoxic BMSCs to TNBC targets NFIX and activates Wnt/β-Catenin signaling in TNBC. Deletion of miR-210-3p in hypoxic BMSC-derived exosomes attenuates TNBC in vivo. Additionally, human exosomal miR-210-3p from the serum of TNBC patients promotes TNBC progression. Moreover, we notably observed a marked downregulation of NFIX expression levels in cancerous tissues compared to paracancerous tissues. Conclusions Hypoxic BMSC-derived exosomal miR-210-3p promotes TNBC progression via NFIX-Wnt/β-catenin signaling axis.

Abstract Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-COV-2, Influenza A, B, and respiratory syncytial virus with a sensitivity of 10 copies/mL. When integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single-copy spatial resolution of 0.83 copies/m3 for airborne virus surveillance with an air flow rate of 400 L/min and a sampling time of 30 minutes. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.

Abstract This paper addresses the challenge of low detection accuracy of grape clusters caused by scale differences, illumination changes, and occlusion in realistic and complex scenes. We propose a multi-scale feature fusion and augmentation YOLOv7 network to enhance the detection accuracy of grape clusters across variable environments. First, we design a Multi-Scale Feature Extraction Module (MSFEM) to enhance feature extraction for small-scale targets. Second, we propose the Receptive Field Augmentation Module (RFAM), which uses dilated convolution to expand the receptive field and enhance the detection accuracy for objects of various scales. Third, we present the Spatial Pyramid Pooling Cross Stage Partial Concatenation Faster (SPPCSPCF) module to fuse multi-scale features, improving accuracy and speeding up model training. Finally, we integrate the Residual Global Attention Mechanism (ResGAM) into the network to better focus on crucial regions and features. Experimental results show that our proposed method achieves a mAP $$_{0.5}$$ 0.5 of 93.29% on the GrappoliV2 dataset, an improvement of 5.39% over YOLOv7. Additionally, our method increases Precision, Recall, and F1 score by 2.83%, 3.49%, and 0.07, respectively. Compared to state-of-the-art detection methods, our approach demonstrates superior detection performance and adaptability to various environments for detecting grape clusters.

Abstract Nucleic acid tests are essential for the accurate diagnosis and control of infectious diseases. However, current assays are not easily scalable for a large population, due to the requirement of laboratory settings or special equipment. Here, we developed an integrated box for instant nucleic acid screening which fully integrates nucleic acid release, amplification, and results visualization for self-service standalone test. Importantly, the operation of the box runs on a novel gamepad-like interface, which allows deployment of the box in home settings and operation by users without any prior professional training. The performance of the box is empowered by an RNA extraction-free sample inactivation process and nested recombinase polymerase amplification chemistry and exhibits sensitivity comparable to reverse transcription-quantitative polymerase chain reaction with high specificity for severe acute respiratory syndrome coronavirus 2 RNA in a reaction time of 30 minutes directly from fresh swab sample to results. These innovations make the box a novel platform for a convenient, accurate, and deployable point-of-care testing scheme.

The graphite layers are combined with van der Waals forces. During the charging and discharging process, the graphite layer spacing changes, causing the graphite flakes to peel off and pulverize, resulting in unsatisfactory electrical cycle performance. In addition, lithium ions can only be inserted from the end surface of the graphite, Will inevitably cause the increase of lithium-ion diffusion resistance, and affect the battery rate performance. In this paper, a sodium salt of perylene tetracarboxylic acid dianhydride is used. By adjusting different coating modification processes, the graphite anode particles coated with sodium salt of perylene tetracarboxylic acid dianhydride are further calcined at high temperature to obtain a graphite-like structure The amorphous hard carbon-coated modified graphite anode material, through comparison, it is found that different thicknesses (9–40 nm) of organic carbon coating show different surface morphologies, which effectively improves the structural stability of the graphite anode material. Performance, and finally obtain more excellent capacity, cycle stability performance and rate performance. [ABSTRACT FROM AUTHOR]

Liver cancer is a malignant tumor found worldwide. mRNA turnover 4 homolog (MRTO4) is highly expressed in hepatocellular carcinoma (HCC) tissues, and we explored its relationship with HCC. All cancer data were downloaded from the Cancer Genome Atlas (TCGA), the Cancer Immune Atlas (TCIA), and the Human Protein Atlas (THPA). Stromal scores, immune scores, and ESTIMATE scores were calculated by “ESTIMATE” R package. Single sample gene set enrichment analysis and CIBERSORT were used to evaluate the immune status and infiltration of cancer tissues. pRRophetic R package was used to predict the half-maximal inhibitory concentration (IC50) of different drugs in each sample. MRTO4 overexpression was associated with poor prognosis in HCC, and positively correlated with the stage and grade of HCC patients. The average immunophenoscore (IPS) of the low MRTO4 group was significantly higher than that of the high MRTO4 group. Tumor microenvironment (TME) scores were significantly higher in the low MRTO4 group than in the high MRTO4 group in HCC. MRTO4 expression was positively correlated with tumor mutation burden (TMB) and was positively correlated with most immune checkpoint gene expressions in HCC. Drug sensitivity analysis showed significantly higher IC50 values for 5-fluorouracil, gemcitabine, and sorafenib in patients with low MRTO4 expression than in those with high MRTO4 expression. MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with clinical stage, tumor grade, and drug sensitivity in HCC. It may serve as a putative therapeutic target and potential biomarker for prognosis of HCC.

Abstract Emerging diagnostic scenarios, such as population surveillance by pooled testing and on‐site rapid diagnosis, highlight the importance of advanced microfluidic systems for in vitro diagnostics. However, the widespread adoption of microfluidic technology faces challenges due to the lack of standardized design paradigms, posing difficulties in managing macro‐micro fluidic interfaces, reagent storage, and complex macrofluidic operations. This paper introduces a novel modular‐based mesoscopic design paradigm, featuring a core “needle‐plug/piston” structure with versatile variants for complex fluidic operations. These structures can be easily coupled with various microfluidic platforms to achieve truly self‐contained microsystems. Incorporated into a “3D extensible” design architecture, the mesoscopic design meets the demands of function integration, macrofluid manipulations, and flexible throughputs for point‐of‐care nucleic acid testing. Using this approach, an ultra‐sensitive nucleic acid detection system is developed with a limit of detection of ten copies of SARS‐CoV‐2 per mL. This system efficiently conducts large‐scale pooled testing from 50 pharyngeal swabs in a tube with an uncompromised sensitivity, enabling a truly “sample‐in‐answer‐out” microsystem with exceptional performance.

Objective It was shown that microRNAs (miRNAs) play an important role in milk protein synthesis. However, the post-transcriptional regulation of casein expression by exogenous miRNA (xeno-miRNAs) in ruminants remains unclear. This study explores the regulatory roles of alfalfa xeno-miR162 on casein synthesis in bovine mammary epithelial cells (bMECs). Methods The effects of alfalfa xenomiR-162 and G protein subunit gamma 11 (GNG11) on proliferation and milk protein metabolism of bMECs were detected by 5-Ethynyl-2′-Deoxyuridine (EdU) staining, flow cytometry, cell counting kit-8 (CCK-8), enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. Dual-luciferase reporter assay was used to verify the targeting relationship between GNG11 and xenomiR-162. Results Results showed that over-expression of xenomiR-162 inhibited cell proliferation but promoted apoptosis, which also up-regulated the expression of several casein coding genes, including CSN1S1, CSN1S2, and CSN3, while decreasing the expression of CSN2. Furthermore, the targeting relationship between GNG11 and xenomiR-162 was determined, and it was confirmed that GNG11 silencing also inhibited cell proliferation but promoted apoptosis and reduced the expression of casein coding genes and genes related to the mammalian target of rapamycin (mTOR) pathway. Conclusion Alfalfa xenomiR-162 appears to regulate bMECs proliferation and milk protein synthesis via GNG11 in the mTOR pathway, suggesting that this xeno-miRNA could be harnessed to modulate CSN3 expression in dairy cows, and increase κ-casein contents in milk.

In order to optimize the detection effect of audio electrical perspective, based on the exploration principle of audio electric perspective, combined with the underground exploration layout, an efficient and accurate mine audio electric perspective detection system is proposed by adopting integrated power supply network of mine audio electric perspective as detection mode, centralized control mode of power supply port and quasi-synchronous measurement method as data acquisition optimization mode. The results show that this system can optimize the construction mode of audio electrical perspective exploration, improve the efficiency of exploration, ensure the accuracy of detection, and realize the efficient and accurate detection of working face audio electrical perspective. The detection effect is ideal and the results are reliable.

In this paper, a double association-based evolutionary algorithm (denoted as DAEA) is proposed to solve many-objective optimization problems. In the proposed DAEA, a double association strategy is designed to associate solutions with each subspace. Different from the existing association methods, the double association strategy takes the empty subspace into account and associates it with a promising solution, which can facilitate the exploration of unknown areas. Besides, a new quality evaluation scheme is developed to evaluate the quality of each solution in subspace, where the convergence and diversity of each solution is first measured, and in order to evaluate the diversity of solutions more finely, the global diversity and local diversity is designed to measure the diversity of each solution. Then, a dynamic penalty coefficient is designed to balance the convergence and diversity by penalizing the global diversity distribution of solutions. The performance of DAEA is validated by comparing with five state-of-the-art many-objective evolutionary algorithms on a number of well-known benchmark problems with up to 20 objectives. Experimental results show that our DAEA has high competitiveness in solving many-objective optimizatiopn problems compared with the other compared algorithms.

Objective: Anterior cervical corpectomy and fusion (ACCF) has been widely used in the treatment of cervical spondylotic myelopathy (CSM) but is accompanied by unavoidable motion loss and destruction of vertebra. We aim to evaluate the range of motion (ROM) of caprine cervical spine constructs implanted with cervical artificial disc and vertebra system (ADVS). The purpose of this study was to investigate the biomechanical properties of the ADVS from an in vivo caprine cervical spine non-fusion model. Methods: Twelve goats were randomly divided into ADVS or control group, with 6 animals in each group. The animals in the ADVS group were implanted with ADVS at the C4 level. The cervical spine constructs were harvested 6 months after the operation. The ROM of cervical spine specimens in the ADVS group was recorded. Biomechanical testing of the specimens in the control group were conducted to evaluate the ROM of the cervical spine specimens under intact and fixed condition (C3-C5) by an anterior plate, respectively. Results: The biomechanical outcomes showed that the ROM of the levels (C3-C5) implanted with ADVS was maintained. The ROM in the adjacent level (C2-3) did not increase significantly comparing with intact group. Conclusions: In general, ADVS could preserve the ROM of operative levels and could reconstruct the height of the vertebra. ADVS did not increase the ROM of upper adjacent level. This device provides a non-fusion method for the treatment of patients suffering from CSM. However, improvements on the design of ADVS are still needed. Translational potential statement: This study introduced a novel cervical spinal implant, which was designed to have the ability of motion preservation and vertebra construction. Our study provided a non-fusion procedure in the treatment of CSM after ACCF.