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Abstract Purpose To investigate the correlation between whole eye movement (WEM) parameters measured using Corvis ST and axial length (AL) to explore whether AL affects WEMs. Methods This single-center, cross-sectional study included data from healthy subjects and patients preparing for refractive surgery at the Qingdao Eye Hospital of Shandong First Medical University. Data were collected from July 2021 to April 2022. We first determined the correlations of WEMs at the time of corneal first applanation (A1_WEM), highest concavity (HC_WEM), and second applanation (A2_WEM), as well as the maximum value of WEM (WEM_Max) with AL. Subsequently, we established a series of regression models to analyze the relationships between different WEM values and AL. Results AL was negatively correlated with HC_WEM, A2_WEM, and WEM_Max (r = − 0.28, − 0.23, and − 0.22, respectively; P

Abstract Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

ABSTRACT This study aims to elucidate additional mutation loci associated with fluoroquinolone (FQ) resistance and evaluate the discriminatory capacity of mutation loci and allele mutation frequencies in identifying FQ-resistant Mycobacterium tuberculosis (MTB) isolates. A random selection of isolates was extracted from an ongoing collection. Drug resistance was determined using the resazurin microtiter assay (REMA) as the gold standard. Mutation loci and the burden of mutations in the quinolone resistance-determining region (QRDR) were elucidated through whole-genome sequencing (WGS). Novel amino acid mutations, namely, G520D and G520T, were identified in the gyrB and associated with FQ resistance. In the context of distinguishing FQ-resistant isolates, the AUC for the QRDR mutation frequency burden (0.969) surpassed that of the mutation locus (0.929), and this difference was statistically significant (P = 0.03). Furthermore, using the resistance mutation locus as a reference, setting the QRDR mutation frequency burden threshold at 1.31% resulted in a 3.60% increase in the accuracy of classifying FQ-resistant isolates (NRI = 3.60%, P < 0.001). The QRDR mutation frequency burden appears to offer superior diagnostic efficacy in discriminating FQ-resistant isolates compared to qualitative detection of mutant loci.IMPORTANCEFluoroquinolone (FQ) drugs are recommended as second-line drugs for the treatment of multidrug-resistant tuberculosis. With the massive use of FQ drugs in the clinical treatment of tuberculosis (TB), there is an increasing rate of drug resistance to FQ drugs. In this study, we identified and demonstrated novel amino acid mutations associated with FQ resistance in Mycobacterium tuberculosis (MTB), and we quantified the mutation sites and identified the quinolone resistance-determining region (QRDR) mutation frequency burden as a novel diagnostic method for FQ resistance. We hope that the results of this study will provide data support and a theoretical basis for the rapid diagnosis of FQ-resistant MTB.

Based on the day and night precipitation data of 64 stations in the Loess Plateau of China from 1961 to 2020 from the National Meteorological Information Center， the Loess Plateau is divided into two regions （monsoon region and westerly region）.The variation characteristics of daytime and nighttime precipitation days and precipitation in the two regions in two seasons （wet-season and dry-season） were analyzed using methods such as linear trend and t test.The main conclusions are as follows： There are significant seasonal differences in daytime and nighttime precipitation between the monsoon region and the westerly region of the Loess Plateau.The number of daytime and nighttime precipitation days in the wet-season （May-September） in the monsoon region accounts for 60% of the whole year， and the precipitation is more than 75%.In the westerly region， the proportion of daytime and nighttime precipitation in the whole year is nearly 70%， and the precipitation is more than 80%.The Loess Plateau tends to get wet in the westerly area and dry in the monsoon area.Among them， the most prominent feature is that in the westerly region， The number of stations which measured increase in daytime accounts for 77.8% of the total.in the wet-season， and more than 50% in the dry-season.In the monsoon area， the number of stations in daytime and nighttime which measured decrease in precipitation days and precipitation account for more than 80% and 50% respectively in the wet-season， and more than 95% and 80% respectively in the dry-season.

Abstract Hyperlipidemia, a common metabolic disease, is a risk factor for cardiovascular diseases, Poria cocos (PC) and Alismatis rhizoma (AR) serve as a potential treatment. A systematic approach based on transcriptome sequencing analysis and bioinformatics methods was developed to explore the synergistic effects of PC–AR and identify major compounds and potential targets. The phenotypic characteristics results indicated that the high dose (4.54 g/kg) of PC–AR reduced total cholesterol (TC), elevated high-density lipoprotein cholesterol (HDL-C) levels, and improved hepatocyte morphology, as assessed via hematoxylin and eosin (H&E) staining. Transcriptomic profiling processing results combined with GO enrichment analysis to identify the overlapping genes were associated with inflammatory responses. The cytokine-cytokine receptor interaction pathway was found as a potential key pathway using geneset enrichment analysis. Core enrichment targets were selected according to the PC–AR's fold change versus the model. Real-time quantitative PCR analysis validated that PC–AR significantly downregulated the expression of Cxcl10, Ccl2, Ccl4, Cd40 and Il-1β mRNA (P

Mycobacterium tuberculosis (Mtb), as a typical intracellular pathogen, possesses several putative restriction–modification (R-M) systems, which restrict exogenous DNA’s entry, such as bacterial phage infection. Here, we investigate Rv2528c, a putative Mrr-like type IV restriction endonuclease (REase) from Mtb H37Rv, which is predicted to degrade methylated DNA that contains m6A, m5C, etc. Rv2528c shows significant cytotoxicity after being expressed in Escherichia coli BL21(DE3)pLysS strain. The Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay indicates that Rv2528c cleaves genomic DNA in vivo. The plasmid transformation efficiency of BL21(DE3)pLysS strain harboring Rv2528c gene was obviously decreased after plasmids were in vitro methylated by commercial DNA methyltransferases such as M.EcoGII, M.HhaI, etc. These results are consistent with the characteristics of type IV REases. The in vitro DNA cleavage condition and the consensus cleavage/recognition site of Rv2528c still remain unclear, similar to that of most Mrr-family proteins. The possible reasons mentioned above and the potential role of Rv2528c for Mtb were discussed.

Toxin-antitoxin (TA) systems are the major mechanism for persister formation in Mycobacterium tuberculosis (Mtb). Previous studies found that HigBA2 (Rv2022c-Rv2021c), a predicted type II TA system of Mtb, could be activated for transcription in response to multiple stresses such as anti-tuberculosis drugs, nutrient starvation, endure hypoxia, acidic pH, etc. In this study, we determined the binding site of HigA2 (Rv2021c), which is located in the coding region of the upstream gene higB2 (Rv2022c), and the conserved recognition motif of HigA2 was characterized via oligonucleotide mutation. Eight binding sites of HigA2 were further found in the Mtb genome according to the conserved motif. RT-PCR showed that HigA2 can regulate the transcription level of all eight of these genes and three adjacent downstream genes. DNA pull-down experiments showed that twelve functional regulators sense external regulatory signals and may regulate the transcription of the HigBA2 system. Of these, Rv0903c, Rv0744c, Rv0474, Rv3124, Rv2603c, and Rv3583c may be involved in the regulation of external stress signals. In general, we identified the downstream target genes and possible upstream regulatory genes of HigA2, which paved the way for the illustration of the persistence establishment mechanism in Mtb.

The stress–strain index (SSI) is a measure of corneal material stiffness, which is obtained using the Corvis ST algorithm based on dynamic corneal response parameters. The reduced SSI corresponds to the longer axial length (AL). In a previous study, we found SSI increases as the corneal curvature flattens, whereas a flatter corneal curvature indicates a longer AL (emmetropia or myopia). Therefore, in this cross-sectional study, we aimed to address these contradictory findings. First, we characterized the features of SSI, curvature radius of the anterior corneal surface (CR), and AL and analyzed their correlation with advanced myopia. Next, we compared the relationship between AL and SSI after adjusting for the effect of CR. We found a significant positive correlation between SSI and CR, which contradicts the developmental law of axial myopia. Furthermore, after accounting for the effect of CR, we observed a stronger correlation between SSI and AL than that in the unadjusted model. In conclusion, CR is an independent influencing factor for SSI in addition to AL, which masked the decrease in SSI caused by prolonged AL in axial myopia.

Objective To establish RH gene mRNA sequencing method based on nanopores sequencing and to explore the RHD and RHCE mRNA transcripts in D positive and Del individuals. Methods From March 2021 to May 2022, 5 RhD positive samples and 5 Del samples screened out by hospitals in Chengdu were sent to our laboratory for futher examination. The erythrocytes and buff coat were isolated, then DNA and RNA were extracted.All 10 samples were genotyped by PCR-SSP. After the mRNA was reversely transcribed into cDNA, the full-length mRNA of RHD and RHCE genes were simultaneously amplified by a pair of primers. Sanger sequencing and third-generation sequencing technology based on Nanopore were used to sequence the amplified products, and the types and expressions of different splices of RHD and RHCE gene mRNA transcripts were analyzed. Results The method established in this study can simultaneously amplify the full length transcripts of RHD and RHCE. Ten different RHD gene mRNA transcripts and nine RHCE gene mRNA transcripts were detected in 10 samples. RHD full-length transcript (RHD-201) can be detected in RhD Del type, but the expression amount was significantly lower than that in RhD positive samples. The expression amount of transcript RHD-207 (Del789) in Del samples was significantly higher than that in RhD positive samples. The transcript RHD-208 (Del8910+ 213) was only detected in RhD Del type individuals, and no significant difference was found between other RHD transcripts and all RHCE transcripts in the two phenotypes. Conclusion In this study, an analytical method for sequencing full-length transcript isomers of RHD and RHCE mRNA via the third generation was successfully established, and complex alternative splicing patterns were found in RHD and RHCE genes, providing a new method for the study of alternative splicing of blood group gene variants mRNA.

Objective To evaluate the association between prophylactic plasma transfusion and postoperative bleeding rate in critically ill patients undergoing different invasive procedures. Methods The information of ICU patients who received different invasive procedures from January 2019 to December 2019 in 6 tertiary hospitals in China were retrospectively investigated. The inclusion criteria of patients were as follows: age ≥ 18 years; received invasive procedures; INR ≥ 1.5 within 72 hours before surgery. Exclusion criteria were patients with incomplete case records. The patients finally included in the study were divided into prophylactic plasma transfusion group and non-prophylactic plasma transfusion group according to their plasma transfusion status. The outcome variable was the incidence of invasive procedure-related bleeding within 48 hours after different invasive procedures. Results A total of 407 patients underwent invasive procedures, and 362 patients were finally included in this study after excluding 45 patients with incomplete case records. The proportions of prophylactic plasma transfusion in different types of invasive procedures were central venous catheterization (46/146, 31.5%), thoracentesis (13/37, 35.1%), bronchoscopy (8/31, 25.8%), tracheal intubation (9/38, 23.7%), arterial catheterization (9/50, 18.0%) and others (13/60, 21.7%). The bleeding rates showed that different invasive procedures presented no statistical difference between the groups received plasma transfusion or not. In the prophylactic plasma transfusion group, the bleeding rate of arterial catheterization (4/9, 44.4%) was the highest, but all were potential bleeding, followed by tracheal intubation (4/10, 40.0%) and central venous intubation (16/46, 34.8%), with a higher rate of significant bleeding. Conclusion Prophylactic infusion of plasma did not reduce the bleeding rate after different invasive procedures, but prospective studies are needed to further confirm the conclusion; this study also provides a certain data basis for later prospective studies.

Interfacial ferroelectricity may emerge in moiré superlattices. Here, the authors find that the polarized charge is much larger than the capacity of the moiré miniband and the associated anomalous screening exists outside the band.

Driven by the minimization of total energy, the multi-domain morphology is preferred in as-grown ferroelectrics to reduce the depolarization and strain energy during the paraelectric to ferroelectric phase transition. However, the complicated multi-domain is not desirable for certain high-performance ferroelectric electro-optic devices. In this work, we achieve a reproducible and stable large-area monodomain in as-grown bulk ferroelectric single crystal [Formula: see text]. The monodomain dominates the entire single crystal, which is attributed to the internal charge carriers from the photoexcited disproportionation reaction of Sn ions. The charge carriers effectively screen the depolarization field and therefore decrease the depolarization energy and facilitate the formation of monodomain. This work offers a potential approach for engineering bulk ferroelectrics with a stable monodomain, which is desirable for the high-performance ferroelectric electro-optic devices.

Abstract Background Patients may be endangered if new graduate nurses cannot recognize and manage anaphylactic shock. Consequently, enhancing the new graduate nurses’ understanding of their roles and responsibilities during the rescue of a patient with anaphylactic shock is important. However, due to its inherent limitations, traditional classroom-based teaching makes it difficult to explore the potential of the students. Although popular simulation teaching has several notable advantages, it has not been proven to be effective in training inexperienced nurses on anaphylactic shock. We investigated the effect of a standardized patient-based simulation on the behaviors of new graduate nurses’ during anaphylactic shock rescue to identify an effective and safe method for contemporary nursing education. Methods Except for the ill or pregnant, all the new graduate nurses were included in the study as students to undergo a standardized patient-based simulation conducted in the clinical skills center of a general hospital. The simulation training was designed to teach students to recognize the signs and symptoms of anaphylactic shock, place the patient in the correct position, stop the ongoing intravenous infusion of the antibiotic which triggers the anaphylactic shock, restart an intravenous infusion on a new infusion apparatus, give 100% oxygen via a nasal cannula or mask, preserve airway patency, call the rapid response team, and correctly administer the medications prescribed by the clinicians. Before and after the training, the instructors evaluated each student’s skills and behaviors using a clinical competency evaluation list. After the training, all students completed the Chinese version of the Simulation Design Scale (SDS) to demonstrate their satisfaction with the program and then participated in semi-structured interviews with their instructors. Results All 104 graduate nurses had a significant improvement on the 6 competencies of the clinical competency evaluation list after the simulation training (P

Purpose: To investigate the relationship between the corneal material stiffness parameter stress-strain index (SSI) and axial length (AL) elongation with varying severities of myopia, based on a mathematical estimation model.Methods: This single-center, cross-sectional study included data from healthy subjects and patients preparing for refractive surgery in the Qingdao Eye Hospital of Shandong First Medical University. Data were collected from July 2021 to April 2022. First, we performed and tested an estimated AL model (ALMorgan) based on the mathematical equation proposed by Morgan. Second, we proposed an axial increment model (ΔAL) corresponding to spherical equivalent error (SER) based on ALemmetropia (ALMorgan at SER = 0) and subject’s real AL. Finally, we evaluated the variations of ΔAL with SSI changes based on the mathematical estimation model.Results: We found that AL was closely associated with ALMorgan (r = 0.91, t = 33.8, p < 0.001) with good consistency and SER was negatively associated with ΔAL (r = −0.89, t = −30.7, p < 0.001). The association of SSI with AL, ALemmetropia, and ΔAL can be summarized using the following equations: AL=27.7−2.04×SSI, ALemmetropia=23.2+0.561×SSI, and ΔAL=4.52−2.6×SSI. In adjusted models, SSI was negatively associated with AL (Model 1: β = −2.01, p < 0.001) and ΔAL (Model 3: β = −2.49, p < 0.001) but positively associated with ALemmetropia (Model 2: β = 0.48, p < 0.05). In addition, SSI was negatively associated with ΔAL among subjects with AL ≥ 26 mm (β = −1.36, p = 0.02).Conclusion: AL increased with decreasing SSI in myopia.

Objective To analyze the genetic background of RhD-negative blood donors by detecting RHD and RHCE genes of those donors. Methods From March 2021 to May 2022, the blood samples of RhD-negative blood donors, who had been screened out by RhD primary screening and confirmatory experiments in the Yaan Blood Center, were firstly identified whether the RHD allele was completely deleted, then whether there were deletions in 10 exons of non-RHD allele complete deletion samples, finally, the remaining samples without RHD alleles and exon deletions were further analyzed by DNA sequencing. RHCE gene was detected by SSP-PCR method. Results Among the RHD gene test results of 104 RhD-negative samples, 65 cases were completely deleted (d/d), 33 were RHD partially deleted (one allele deletion), and 6 were without RHD gene deletion. The RHD alleles of 33 samples with partial deletion were detected by 10 exons, 13 had partial exon deletion, with genotype as RHD*D-CE(3-9)-D/d and phenotype as RhD negativity, and the remaining 20 samples had no exon deletion. The exon sequencing results of the non-deletion samples showed RHD*1227A/RHD*1227A in 6 samples, RHD*1227A/d in 19, RHD*3A/d in 1; both of the last two were considered Del by ISBT. The RHCE gene test results showed that all cc genotype blood donors were RhD true negative, while Del blood donors had no cc genotype. Conclusion Through the genetic background study of RhD negative blood donors, it is found that there is a high proportion of Del with weak expression of RhD antigen, whether this blood type affects clinical blood safety needs further researches.

Plasma is widely used in clinical, but the reliable evidence-based medical evidences that can guide clinicians to properly use plasma are limited, and inappropriate use may even cause deterioration of the disease and serious adverse reactions. Based on the relevant international blood transfusion guidelines and published clinical trial studies, this paper aims to summarize the evidence-based basis of plasma in clinical applications, discuss the safety and efficacy of plasma applications under different conditions, and provide assistance to clinical practice and scientific research of plasma in the future.

Convolutional neural network (CNN) is widely used in hyperspectral image (HSI) classification owing to their advantages of spatial-spectral features capture capability and learning depth features as well as their structural flexibility. Nevertheless, the shape of the convolution kernel is fixed, a limitation that leads to shape fixation when modeling different features in CNN, especially in the edge regions between classes. A multiscale adaptive convolution (MSAC) model is proposed in this article to overcome this shortcoming. Combining superpixels with the traditional convolutional kernels to form adaptive kernels automatically adjusts the receptive field, suppresses edge noise, and enhances feature learning for different classes. On the basis of adaptive convolution, adaptive convolution units (AConvUs) are constructed. The hierarchical residual structure is constructed by superimposing multiple AConvUs to learn the spatial spectral features of different receptive fields of the HSI, reduce the gradient disappearance and enhance the robustness. The proposed multiscale convolution adjusts the shape of the convolution kernel according to the spatial distribution of different superpixels in HSI. Finally, the MSAC classification framework is constructed by the decision fusion of multiscale adaptive convolution at different superpixel scales, which helps to extract the complementary information of the HSI. The MSAC method’s experimental performance on several HSI datasets, including Indian Pines, University of Pavia, Salinas and Gaofen-5, to verify the validity and practically.

The pavement of bus rapid transit (BRT) stations is subjected to highly channelized load caused by buses, which can cause serious distresses and may lead to early failure. For asphalt pavements, rutting is the most common distress under such conditions. In this study, a case study of the latest BRT paving project in Chengdu, China was introduced. Two asphalt mixtures were designed to serve as the station pavement surface. PG 76-22 asphalt was modified with high viscosity and high modulus addictive to further improve its mechanical properties. The effects of the modification were validated by a series of Hamburg wheel tracking tests. The test results suggested that gap-graded mix performed better in rutting resistance than dense-graded specimens. Modification with high viscosity agents could significantly inhibit rutting propagation. If the mix was modified with both high viscosity and high modulus agents, it would be able to avoid stripping under the most severe test condition. As for project implementation, a life cycle cost analysis was carried out to compare different paving plans. The construction process of BRT pavement was elaborated with detailed description and photos, explaining base treatment, paving, compaction, and quality control, which could help guide the construction of future BRT paving projects.

Smartphone-assisted fluorescence and colorimetric methods for the on-site detection of Hg2+ and Cl− were established based on the oxidase-like activity of the Au–Hg alloy on the surface of Au/Cu/Ti3C2 NSs. The Au nanoparticles (NPs) were constructed via in-situ growth on the surface of Cu/Ti3C2 NSs and characterized by different characterization techniques. After the addition of Hg2+, the formation of Hg–Au alloys could promote the oxidization of o-phenylenediamine (OPD) to generate a new fluorescence emission peak of 2,3-diaminopenazine (ADP) at 570 nm. Therefore, a turn-on fluorescence method for the detection of Hg2+ was established. As the addition of Cl− can influence the fluorescence of ADP, the fluorescence intensity was constantly quenched to achieve the continuous quantitative detection of Cl−. Therefore, a turn-off fluorescence method for the detection of Cl− was established. This method had good linear ranges for the detection of Hg2+ and Cl− in 8.0–200.0 nM and 5.0–350.0 µM, with a detection limit of 0.8 nM and 27 nM, respectively. Depending on the color change with the detection of Hg2+ and Cl−, a convenient on-site colorimetric method for an analysis of Hg2+ and Cl− was achieved by using digital images combined with smartphones (color recognizers). The digital picture sensor could analyze RGB values in concentrations of Hg2+ or Cl− via a smartphone app. In summary, the proposed Au/Cu/Ti3C2 NSs-based method provided a novel and more comprehensive application for environmental monitoring.

Abstract We aimed to elucidate the differences in genomic methylation patterns between ADLI and non-ADLI patients to identify DNA methylation-based biomarkers. Genome-wide DNA methylation patterns were obtained using Infinium MethylationEPIC (EPIC) BeadChip array to analyze 14 peripheral blood samples (7 ADLI cases, 7 non-ADLI controls). Changes in the mRNA and DNA methylation in the target genes of another 120 peripheral blood samples (60 ADLI cases, 60 non-ADLI controls) were analyzed by real-time polymerase chain reaction and pyrosequencing, respectively. A total of 308 hypermethylated CpG sites and 498 hypomethylated CpG sites were identified. Significantly, hypermethylated CpG sites cg06961147 and cg24666046 in TANC1 associated with ADLI was identified by genome-wide DNA methylation profiling. The mRNA expression of TANC1 was lower in the cases compared to the controls. Pyrosequencing validated these two differentially methylated loci, which was consistent with the results from the EPIC BeadChip array. Receiver operating characteristic analysis indicated that the area under the curve of TANC1 (cg06961147, cg24666046, and their combinations) was 0.812, 0.842, and 0.857, respectively. These results indicate that patients with ADLI have different genomic methylation patterns than patients without ADLI. The hypermethylated differentially methylated site cg06961147 combined with cg24666046 in TANC1 provides evidence for the diagnosis of ADLI.

Purpose: This study aimed to investigate the correlation of axial length/corneal radius of curvature ratio with stress–strain index (SSI).Methods: Retrospective analysis was conducted to compare the right eyes of those with high myopia (HM, n = 132; age and 10–48 years) with those without high myopia (NHM, n = 135; age and 7–48 years), where the baseline axial length, corneal radius of curvature ratio, and central corneal thickness were analyzed; the differences in two groups were compared; and the relationship of axial length and axial length/corneal radius of curvature ratio with SSI were explored.Results: Compared with AL < 26mm, SSI significantly decreased when AL ≥ 26 mm (p = 0.001), while there was no correlation with AL in the NHM group (r = -0.14, p = 0.12) or HM group (r = -0.09, p = 0.32). AL/CR was significantly associated with SSI in both the NHM (r = -0.4, p < 0.001) and HM (r = -0.18, p = 0.04) groups. In the NHM group, AL/CR was significantly associated with SSI (unstandardized beta = -0.514, se = 0.109, p < 0.001) with the adjustment of age and gender. Additionally, a significant association of SSI with AL/CR was also found after adjusting for age and gender (unstandardized beta = -0.258, se = 0.096, and p = 0.0082) in the HM group.Conclusion: SSI showed a significant negative correlation with AL/CR in patients without high myopia and in patients with high myopia. However, SSI exhibited no decrease with the worsening of myopia, but it gradually remained stable at a low level. The findings of this study validate, to some extent, the possibility of analyzing the dynamic changes in ocular wall stiffness during the development of myopia by measuring in vivo corneal biomechanical parameters.

Hyperspectral images (HSIs) consist of hundreds of spectral bands, which can be used to precisely characterize different land cover types. However, an HSI has redundant information and is prone to the “dimensionality curse.” Therefore, it is necessary to reduce redundant information through dimensionality reduction (DR), given that different dimensions contain unique primary feature information, and the feature information is complementary. Accordingly, a new feature extraction method based on multidimensional spectral regression whitening (M-SRW) is proposed, which reduces HSI to different dimensions and reconstructs it for feature extraction. The proposed method consists of the following steps: First, the original HSI is superpixel segmented by the entropy rate segmentation algorithm. Second, SRW is performed in each superpixel block to reduce the dimension of each superpixel block to a different dimension. Third, superpixel blocks of the same dimension are combined to obtain the reconstructed HSI. Finally, the support vector machine is utilized to classify the reconstructed HSI of different dimensions, and majority voting decision fusion is used to obtain the final classification result map. Experiments on three public hyperspectral data sets demonstrated that the proposed M-SRW method is superior to several state-of-the-art feature extraction approaches in terms of classification accuracy.

Abstract As a prevalent tumor among women, breast cancer is still an incurable disease due to drug resistance. In this study, we report microRNA‐221 to have a significant effect on breast cancer resistance to adriamycin. The microRNA‐221 is elevated in tumor tissue compared with nearby nontumor samples, as well as in breast cancer cell line with adriamycin resistance (MCF‐7/ADR) compared to its parental line (MCF‐7) and the normal breast epithelial cell line (MCF‐10A). Enforced level of microRNA‐221 promotes cancer resistance to adriamycin, which in turn sustains cell survival and exacerbates malignant formation. Reciprocally, the silence of microRNA‐221 in cancer cells augments the sensitivity to chemotherapy, thereby resulting in enhanced apoptosis of MCF‐7/ADR cells. Mechanistically, we identify PTEN as a direct target of microRNA‐221, which was conversely associated with a microRNA‐221 level in breast tumors. The knock‐down of PTEN partially reversed the stimulatory role of microRNA‐221 in the modulation of the Akt/mTOR signaling. Taken together, these findings suggest microRNA‐221 suppresses PTEN transcription and activates Akt/mTOR pathway, which in turn enhances breast cancer resistance to adriamycin and promotes cancer development. Our data thus illuminate the microRNA‐221/PTEN axis may act as a promising strategy for the treatment of chemotherapy‐resistant breast tumors.

Objective: Rapamycin is a potent inducer of autophagy in podocytes. However, we still understand very little about how autophagy is regulated under podocyte injury conditions. This study aimed to investigate the role of autophagy in podocyte injury and the regulatory mechanism of the PI3K/Akt/mTOR signaling pathway in this process. Methods: The podocytes were cultured in vitro, and the apoptosis rate of each group was determined by flow cytometry. The protein expression and distribution of LC3-II were examined by immunofluorescence. The phosphorylation levels of Akt, LC3-II, mTOR, 4EBP1, and P70S6K were measured using Western Blot. Transmission electron microscopy was used to examine the changes in autophagosomes in each group. Results: Compared with the control group, the puromycin group (PAN) increased podocyte apoptosis, decreased numbers of autophagosomes, and downregulated LC3-II protein expression. Compared with the PAN group, the podocyte apoptosis rate decreased in the Rapamycin group (RAPA), the number of autophagosomes increased, and LC3-II protein expression was upregulated. In addition, PAN evoked an increase in p-Akt expressions, RAPA treatment induced a reversal of PAN-induced p-Akt upregulation, and the phosphorylation levels of mTOR, 4EBP1, and P70S6K were downregulated. Conclusion: PAN can damage podocytes by inhibiting podocyte autophagic activity and promoting apoptosis. Rapamycin can ameliorate PAN-induced podocyte damage by activating autophagy. This effect may be related to rapamycin-mediated PI3K/AKT/mTOR signaling pathway and autophagy.

Objective. Identifying new markers of juvenile systemic lupus erythematosus (JSLE) is critical event to predict patient stratification and prognosis. The aim of the present study is to analyze alteration of urinary protein expression and screen potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE). Methods. The urine was collected from the patients with or without JSLE and detected by mass spectrometry to analyze proteomic changes. ELISA was used to verify the Vitronectin (VTN) changes in a new set of patients. The clinical correlation was performed to analyze between VTN and clinical pathological parameters. WB and ELISA were used to analyze VTN-mediated cell pyroptosis. Results. Herein, we have identified a group of 105 differentially expressed proteins with ≥1.3-fold upregulation or ≤0.77-fold downregulation in JSLE patients. These proteins were involved in several important biological processes, including acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation through Gene Ontology and functional enrichment analysis. Interestingly, urinary ephrin type-A receptor 4 (EPHA4) and VTN were significantly reduced in both inactive and active JSLE patients, and VTN treatment in THP-1 derived macrophages led to a significant increased cell pyroptosis by activation of Nod-like receptor family protein 3 (NLRP3) inflammasomes, resulting in caspase-1 activation, cleaved gasdermin D (GSDMD), and IL-18 secretion. Most importantly, the urinary VTN was also linearly correlated with clinical characteristics of JSLE, implying that VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE. Conclusion. This study provided a novel role of VTN in pyroptosis in JSLE through the urinary proteomic profile for JSLE, which could be a nonintrusive monitoring strategy in clinical diagnosis.

Background Cardiomyocytes loss is the predominant pathogenic characteristic in the hypoxia-induced injury. Meanwhile, it has been corroborated that Bcl-2 E1B 19-KDa interacting protein 3 (BNIP3) provokes apoptosis and autophagy. For moderating cardiomyocytes loss, we initially probed the cyto-protection effects of 6-Gingerol (6 G), meanwhile, its potential mechanisms associated with BNIP3 were elucidated in our studies.Methods We pretreated cardiomyocytes H9c2 cells with 6 G at different concentrations (0–100 μM) before exposure to hypoxia. Thereafter, the cell viability, lactate dehydrogenase (LDH), apoptosis and protein expression were respectively assessed using cell counting kit-8 and methyl thiazolyl tetrazolium (MTT) assay, LDH assay kit, Annexin V-fluorescein isothiocyannate/propidium iodide (Annexin V-FITC/PI) apoptosis detection kit and Western blotting analysis. In addition, we also analyzed BNIP3 level after treatment. Moreover, we enforced the exogenous overexpression of BNIP3 and then evaluated the cell viability, apoptosis, and protein level again.Results In our present work, we observed that the cell viability was promoted by 6 G in the hypoxia-induced H9c2 cells in a dose-dependent manner. Moreover, hypoxia-induced LDH release, apoptosis and autophagy were inhibited by 6 G pretreatment through promoting phosphorylation of PI3K, AKT and mTOR. Remarkably, accumulation of BNIP3 protein was significantly reduced by 6 G in hypoxia-induced H9c2 cells. Mechanistically, 6 G initiated the phosphorylated expression of PI3K, AKT and mTOR by down-regulating BNIP3 with reducing cardiomyocytes apoptosis and autophagy.Conclusion Hypoxia-induced cardiomyocytes injury was ameliorated by 6 G through suppressing BNIP3 expression with triggering PI3K/AKT/mTOR signalling pathway.

Background Myocardial ischemia is the main reason for ischemic heart disease. Baicalin is a plant-derived flavonoid with cardio-protective activity. Herein, we tested the influences of baicalin on cardiomyocytes H9c2 apoptosis aroused by hypoxia stimulation.Methods Firstly, H9c2 cells were subjected to hypoxia and/or baicalin exposure. Cell viability and apoptosis, along with hypoxia-inducible factor 1α (HIF1α) and Bcl-2/adenovirus E1B 19-KDa interacting protein 3 (BNIP3) expressions were tested respectively. Then, si-HIF1α was transfected into H9c2 cells to probe whether up-regulation of HIF1α attended to the influences of baicalin on hypoxia-stimulated H9c2 cells. Finally, the regulatory effect of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on HIF1α expression was analyzed.Results Hypoxia exposure aroused H9c2 cell viability reduction and apoptosis. Baicalin mitigated H9c2 cell viability reduction and apoptosis aroused by hypoxia. Moreover, HIF1α/BNIP3 pathway was further activated by baicalin in hypoxia-exposed H9c2 cells. Silencing HIF1α lowered the functions of baicalin on hypoxia-exposed H9c2 cells. Besides, baicalin enhanced hypoxia-caused activation of Nrf2/HO-1 pathway. Activation of Nrf2/HO-1 pathway was associated with the up-regulation of HIF1α and protective functions of baicalin on hypoxia-exposed H9c2 cells.Conclusion Baicalin relieved cardiomyocytes H9c2 apoptosis aroused by hypoxia might be achieved through activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway.HighlightsBaicalin mitigates H9c2 cell viability loss and apoptosis aroused by hypoxia;Baicalin activates HIF1a/BNIP3 pathway in hypoxia-exposed H9c2 cells;Silencing HIF1α weakens the influences of baicalin on hypoxia-exposed H9c2 cells;Baicalin promotes Nrf2/HO-1 pathway in hypoxia-exposed H9c2 cells;Promotion of Nrf2/HO-1 pathway is related to the up-regulation of HIF1α.

Convolutional neural networks (CNNs) are widely used for hyperspectral image (HSI) classification due to their better ability to model the local details of HSI. However, CNNs tends to ignore the global information of HSI, and thus lack the ability to establish remote dependencies, which leads to computational cost consumption and remains challenging. To address this problem, we propose an end-to-end Inception Transformer network (IFormer) that can efficiently generate rich feature maps from HSI data and extract high- and low-frequency information from the feature maps. First, spectral features are extracted using batch normalization (BN) and 1D-CNN, while the Ghost Module generates more feature maps via low-cost operations to fully exploit the intrinsic information in HSI features, thus improving the computational speed. Second, the feature maps are transferred to Inception Transformer through a channel splitting mechanism, which effectively learns the combined features of high- and low-frequency information in the feature maps and allows for the flexible modeling of discriminative information scattered in different frequency ranges. Finally, the HSI features are classified via pooling and linear layers. The IFormer algorithm is compared with other mainstream algorithms in experiments on four publicly available hyperspectral datasets, and the results demonstrate that the proposed method algorithm is significantly competitive among the HSI classification algorithms.

Abstract Background In this study, we have investigated the potential regulatory mechanisms of IL‐35 to relieve lupus nephritis (LN) through regulating Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway in mesangial cells. Results Among 105 significant differentially expressed proteins (DEPs) between juvenile systemic lupus erythematosus (JSLE) patients with LN and healthy controls, LAIR1, PDGFRβ, VTN, EPHB4, and EPHA4 were downregulated in JSLE‐LN. They consist of an interactive network with PTPN11 and FN1, which involved in IL‐35‐related JAK/STAT signaling pathway. Besides, urinary LAIR1 was significantly correlated with JSLE‐LN clinical parameters such as SLEDAI‐2K, %CD19+ B, and %CD3+ T cells. Through bioinformatics analysis of co‐immunoprecipitation with mass spectrometry results, including GO, KEGG, and STRING, five genes interacted with Lair1 were upregulated by IL‐35, but only Myh10 was downregulated. Therefore, we presumed an interactive network among these DEPs, JAK/STAT, and IL‐35. Moreover, the downregulated phosphorylated (p)‐STAT3, p‐p38 MAPK, and p‐ERK, and the upregulated p‐JAK2/p‐STAT1/4 in IL‐35 overexpressed mesangial cells, and RNA‐sequencing results validated the potential regulatory mechanisms of IL‐35 in alleviating JSLE‐LN disease. Moreover, the relieved histopathological features of nephritis including urine protein and leukocyte scores, a decreased %CD90+αSMA+ mesangial cells and pro‐inflammatory cytokines, the inactivated JAK/STAT signals and the significant upregulated Tregs in spleen, thymus and peripheral blood were validated in Tregs and IL‐35 overexpression plasmid‐treated lupus mice. Conclusions Our study provided a reference proteomic map of urinary biomarkers for JSLE‐LN and elucidated evidence that IL‐35 may regulate the interactive network of LAIR1‐PTPN11‐JAK‐STAT‐FN1 to affect JAK/STAT and MAPK signaling pathways to alleviate inflammation in JSLE‐LN. This finding may provide a further prospective mechanism for JSLE‐LN clinical treatment.

As one of the major contributors to the early failures of steel bridge deck pavements, the bonding between steel and asphalt overlay has long been a troublesome issue. In this paper, a novel composite bonding structure was introduced consisting of epoxy resin micaceous iron oxide (EMIO) primer, solvent-free epoxy resin waterproof layer, and ethylene-vinyl acetate (EVA) hot melt pellets. A series of strength tests were performed to study its mechanical properties, including pull-off strength tests, dumbbell tensile tests, lap shear tests, direct tension tests, and 45°-inclined shear tests. The results suggested that the bonding structure exhibited fair bonding strength, tensile strength, and shear strength. Anisotropic behaviour was also observed at high temperatures. For epoxy resin waterproof layer, the loss of bonding strength, tensile strength, and shear strength at 60°C was 70%, 35%, and 39%, respectively. Subsequent pavement performance-oriented tests included five-point bending tests and accelerated wheel tracking tests. The impacts of bonding on fatigue resistance and rutting propagation were studied. It was found that the proposed bonding structure could provide a durable and well-bonded interface and was thus beneficial to prolong the fatigue lives of asphalt overlay. The choice of bonding materials was found irrelevant to the ultimate rutting depth of pavements. But the bonding combination of epoxy resin waterproof and EVA pellets could delay the early-stage rutting propagation.

Abstract Background This investigation aimed to evaluate the role of methylation in the regulation of microRNA (miR)-122, miR-125b and miR-106b gene expression and the expression of their target genes during isoniazid (INH)-induced liver injury. Methods Rats were given INH 50 mg kg− 1·d− 1 once per day for 3, 7, 10, 14, 21 and 28 days and were sacrificed. Samples of blood and liver were obtained. Results We analysed the methylation and expression levels of miR-122, miR-125b and miR-106b and their potential gene targets in livers. Liver tissue pathologies, histological scores and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities changed, indicating the occurrence of liver injury. Relative expression levels of miR-122, miR-125b and miR-106b genes in the liver decreased after INH administration and correlated with the scores of liver pathology and serum AST and ALT activities, suggesting that miR-122, miR-125b and miR-106b are associated with INH-induced liver injury. The amount of methylated miR-122, miR-125b and miR-106b in the liver increased after INH administration and correlated with their expression levels, suggesting the role of methylation in regulating miRNA gene expression. Two miR-122 gene targets, cell cycle protein G1 (Cyclin G1) and cationic amino acid transporter-1 (CAT-1), also increased at the mRNA and protein levels, which suggests that lower levels of miR-122 contribute to the upregulation of Cyclin G1 and CAT-1 and might play a role in INH-induced liver injury. Signal transducer and activator of transcription 3 (STAT3) was a common target gene of miR-125b and miR-106b, and its expression levels of mRNA and protein increased after INH administration. The protein expression of phosphorylated (p)-STAT3 and the mRNA expression of RAR-related orphan receptor gamma (RORγt) regulated by p-STAT3 also increased. Meanwhile, the mRNA and protein expression of interleukin (IL)-17 regulated by RORγt, and the mRNA and protein expression of CXCL1 and MIP-2 regulated by IL-17 increased after INH administration. These results demonstrate that lower levels of hepatic miR-125b and miR-106b contribute to the upregulation of STAT3 in stimulating the secretion of inflammatory factors during INH-induced liver injury. Conclusions Our results suggested that DNA methylation probably regulates the expression of miRNA genes (miR-122, miR-125b, and miR-106b), affecting the expression of their gene targets (Cyclin G1, CAT-1, and STAT3) and participating in the process of INH-induced liver injury.

High percentage reclaimed asphalt pavement (RAP) is prevailing in pavement engineering for its advantages in sustainability and environmental friendliness, however, its fatigue resistance remains a major concern. Fine aggregate matrix (FAM) is a crucial part in the fatigue resistance of asphalt mixtures with high RAP content. Hence, the linear amplitude sweep (LAS) test of FAM has been developed to study the fatigue resistance of asphalt mixtures. However, the torsional loading mode of the LAS test with a dynamic shear rheometer (DSR) is a limitation to simulate traffic load. In this paper, an alternative LAS test for FAM with high RAP content was proposed. Beam FAM specimens were tested using a dual-cantilever flexural loading fixture in a dynamic mechanical analyzer (DMA). To investigate the influence of RAP content and the rejuvenating agent (RA), four kinds of FAM mixes were tested with this method to study their fatigue resistance. The test results suggested that the repeatability of this alternative approach was reliable. A fatigue failure criterion based on maximum C × N was defined. Then, fatigue life prediction models based on viscoelastic continuum damage (VECD) analysis were established according to the LAS test results and validated by a strain-controlled time sweep (TS) test. It turned out that as RAP content increased, the modulus of FAM would be significantly raised, accompanied with a drop in the phase angle. The fatigue life of FAM would be greatly shortened when the RAP binder replacement rate reached 50%. Adding RA could considerably improve the dynamic properties of FAM mixes with high RAP content, resulting in a decrease in modulus, increase in phase angle and elongating fatigue life, but could not recover to the level of virgin binder.

BackgroundAnti-tuberculosis (anti-TB) drug-induced liver injury (ADLI) is one of the most common adverse effects associated with TB treatment. Cytochrome P450 (CYP) 1A1 and glutathione S-transferase (GST) P1 are important phase I/II metabolizing enzymes involved in drug metabolism and detoxification. Genetic polymorphism and CpG island methylation have been reported as factors influencing the expression of CYP1A1 and GSTP1.ObjectiveThis study aimed to determine the potential relationships of CYP1A1 and GSTP1 polymorphisms and CpG island methylation with ADLI risk.DesignThis was a population-based one-to-one matched case-control study.SettingThe subjects were patients with TB receiving treatment in China from December 2010 to June 2013.PatientsIn total, 127 patients with TB and ADLI (case group) and 127 patients with TB but without liver injury (control group) were included in this study. Subjects were matched in terms of sex, age, and therapeutic regimen.MethodsThe general condition of each patient was assessed using questionnaires. The CYP1A1 MspI and GSTP1 Ile105Val polymorphisms as well as methylation status were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the methylation-specific PCR method.ResultsWe found no significant difference in GSTP1 and CYP1A1 genotypes between the two groups, probably because the sample size was not large enough; however, patients with ADLI had significantly higher GSTP1 and CYP1A1 promoter methylation rates than control subjects [odds ratio (OR) = 2.467 and 2.000, respectively]. After adjusting for drinking, which significantly differed between the groups as per univariate analysis, we found that hypermethylation of GSTP1 and CYP1A1 promoters was associated with ADLI (OR = 2.645 and 2.090, respectively).ConclusionHypermethylation of CpG islands of GSTP1 and CYP1A1 promoters may thus play important roles in the development of ADLI and provide evidence of being used as novel markers for ADLI risk prediction.