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With the development of tunnel construction, the detection, control, and treatment of all kinds of tunnel lining diseases have received increased attention. Therefore, tunnel nondestructive testing technology is widely used as an intelligent emerging technology. Due to the cost limitations of industrial applications, nondestructive testing technology of medium- and small-shield tunnels experiences serious losses in accuracy and speed when transferred to large-diameter shield tunnels. A large shield tunnel forming quality inspection vehicle is developed by integrating a two-dimensional (2D) laser scanner with a wheel shaft encoder and an industrial computer. Based on this equipment, an asymmetric shield quality inspection method based on digital images is proposed. By analyzing the construction environment of a large-diameter shield tunnel, the ground and vehicle body point clouds are filtered, the central axis is extracted using the neighborhood vector method, and the central coordinate system of the tunnel is established. The inspection route is arranged eccentrically, and the sampling point clouds are divided into dense and sparse side point clouds according to their tunnel density. Moreover, different methods are used to pick up the joint features of the segment. The dense side point cloud is expanded around the central axis into a 2D gray image, and the joint image is segmented by scaling, normalization, and gradient threshold segmentation. According to the classification of joints based on the linear equation, the linear distribution formula of sparse and dense side joints is deduced by combining the segment structure and the point placement, with the sparse side joints picked up indirectly. According to the joint characteristic points, the edge point clusters on both sides of the segment and the segment misalignment are calculated. The least square method is used to fit the tunnel point cloud and calculate tunnel ellipticity. Tests are conducted in a large-diameter shield tunnel to verify the effectiveness of the inspection method, and the following conclusions are made from the test results: The inspection speed of the molding quality inspection vehicle in the 14-meter shield tunnel is 3 km·h−1; compared with traditional detection methods, the average deviation of segment dislocation detection is less than 2 mm; the average deviation of tunnel contour maximum deformation detection is less than 2 mm, and the average deviation of ovality detection is less than 0.1%. This meets the high-speed, high-precision, and low-cost requirements of large-diameter shield tunnel molding quality inspections.

BackgroundThe relationship between plant-based diets and gallstone disease has been debated. This study aimed to shed light on the association between plant-based dietary index and the risk of developing gallstone disease.MethodsEligible participants were selected from National Health and Nutrition Examination Survey (NHANES) 2017-2020. Three plant-based diet indexes (PDI, healthy PDI, unhealthy PDI) were calculated using data from two NHANES 24-h dietary recall interviews. Restricted Cubic Spline and multivariate logistic regression were used to analyze the associations. Subgroup analysis was adopted to make the results more robust.ResultsA total of 5673 eligible participants were analyzed. After adjusting for various confounding variables, uPDI was positively associated with gallstone disease (OR = 1.53, 95%CI: 1.02-2.29). No association was found between PDI/hPDI and gallstone disease (p > 0.05). The results of subgroup analysis did not show any positive association between uPDI and gallstones in specific groups.ConclusionOur study shows that the elevated uPDI are linked to a higher risk of gallstone disease.

We introduce Catalyst.jl, a flexible and feature-filled Julia library for modeling and high-performance simulation of chemical reaction networks (CRNs). Catalyst supports simulating stochastic chemical kinetics (jump process), chemical Langevin equation (stochastic differential equation), and reaction rate equation (ordinary differential equation) representations for CRNs. Through comprehensive benchmarks, we demonstrate that Catalyst simulation runtimes are often one to two orders of magnitude faster than other popular tools. More broadly, Catalyst acts as both a domain-specific language and an intermediate representation for symbolically encoding CRN models as Julia-native objects. This enables a pipeline of symbolically specifying, analyzing, and modifying CRNs; converting Catalyst models to symbolic representations of concrete mathematical models; and generating compiled code for numerical solvers. Leveraging ModelingToolkit.jl and Symbolics.jl, Catalyst models can be analyzed, simplified, and compiled into optimized representations for use in numerical solvers. Finally, we demonstrate Catalyst's broad extensibility and composability by highlighting how it can compose with a variety of Julia libraries, and how existing open-source biological modeling projects have extended its intermediate representation.

Abstract Background Complex manifestation of stigma across personal, community, and structural levels and their effect on HIV outcomes are less understood than effects in isolation. Yet, multilevel approaches that jointly assesses HIV criminalization and personal sexual behavior stigma in relation to HIV testing have not been widely employed or have only focused on specific subpopulations. The current study assesses the association of three types of MSM-related sexual behavior-related stigma (family, healthcare, general social stigma) measured at both individual and site levels and the presence/absence of laws criminalizing HIV transmission with HIV testing behaviors to inform HIV surveillance and prevention efforts among HIV-negative MSM in a holistic and integrated way. Methods We included nine National HIV Behavioral Surveillance (NHBS) 2017 sites: Baltimore, MD; Denver, CO; Detroit, MI; Houston, TX; Long Island/Nassau-Suffolk, NY; Los Angeles, CA; Portland, OR; San Diego, CA; and Virginia Beach and Norfolk, VA. Multivariable generalized hierarchical linear modeling was used to examine how sexual behavior stigmas (stigma from family, anticipated healthcare stigma, general social stigma) measured at the individual and site levels and state HIV criminalization legislation (no, HIV-specific, or sentence-enhancement laws) were associated with past-year HIV testing behaviors across sites (n = 3,278). Results The majority of MSM across sites were tested for HIV in the past two years (n = 2,909, 95.4%) with the average number of times tested ranging from 1.79 (SD = 3.11) in Portland, OR to 4.95 (SD = 4.35) in Los Angeles, CA. In unadjusted models, there was a significant positive relationship between stigma from family and being tested for HIV in the past two years. Site-level HIV-specific criminalization laws were associated with an approximate 5% reduction in the prevalence of receiving any HIV test in the past two years after individual level stigma and sociodemographic covariate adjustments (PR = 0.94, 95% CI, 0.90–0.99). Conclusions Structural barriers faced by MSM persist and ending the HIV epidemic in the US requires a supportive legal environment to ensure effective engagement in HIV services among MSM. Home-based solutions, such as self-testing, used to deliver HIV testing may be particularly important in punitive settings while legal change is advocated for on the community and state levels.

Recent studies have shown that the brain functional connectome constitutes a unique fingerprint that allows the identification of individuals from a group. However, what information encoded in the brain that makes us unique remains elusive. Here, we addressed this issue by examining how individual identifiability changed along the language hierarchy. Subjects underwent fMRI scanning during rest and when listening to short stories played backward, scrambled at the sentence level, and played forward. Identification for individuals was performed between two scan sessions for each task as well as between the rest and task sessions. We found that individual identifiability tends to increase along the language hierarchy: the more complex the task is, the better subjects can be distinguished from each other based on their whole-brain functional connectivity profiles. A similar principle is found at the functional network level: compared to the low-order network (the auditory network), the high-order network is more individualized (the frontoparietal network). Moreover, in both cases, the increase in individual identifiability is accompanied by the increase in inter-subject variability of functional connectivities. These findings advance the understanding of the source of brain individualization and have potential implications for developing robust connectivity-based biomarkers.

Abstract Background Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. Methods The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. Results We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Conclusions Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression.

Previous literature has associated math literacy with linguistic factors such as verbal ability and phonological skills. However, few studies have investigated "linguistic synchrony," shown in mathematical discussions. This study modelled math literacy and examined the relationship of math literacy with linguistic synchrony between students and facilitators. We retrieved data from 20,776 online mathematical discussion threads at a secondary school level. First, we assessed students' math literacy based on their discussions and classified them into high- and low-math literacy groups. Then, we conducted Cross-Recurrence Quantification Analysis (CRQA) to calculate linguistic synchrony within each thread. The result implies that students with high math literacy are more likely to share common words (eg, mathematical terms) with facilitators. At the same time, they would paraphrase the facilitators' words rather than blindly mimic them as the exact sentences or phrases. On the other hand, students with low math literacy tend to use overlapping words with facilitators less frequently and are more likely to repeat the exact same phrases from the facilitators. The findings provide an empirical data analysis and insights into mathematical discussions and linguistic synchrony. In addition, this paper implies the directions to improve online mathematical discussions and foster math literacy.

Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the occurrence of distant tumor metastasis with YAP1-associated anti-angiogenic therapy over time. It provides insight into new pathways and treatment paradigms that may be targeted to increase the long-term success of anti-angiogenic therapies.

Abstract Multivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation pathway. In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. However, the mechanisms by which MVBs are sorted to the lysosome and plasma membrane remain unclear. In addition, whether the trafficking of MVBs can determine whether exosomes are released from cells, the factors are involved in cargo loading and regulating the fate of MVBs, and the roles that MVBs play in the development of disease are unknown. Consequently, this review focuses on the mechanism of MVB biogenesis, intraluminal vesicle formation, sorting of different cargoes, and regulation of their fate. We also discuss the mechanisms of emerging amphisome-dependent secretion and degradation. In addition, we highlight the contributions of MVBs to the heterogeneity of EVs, and their important roles in cancer. Thus, we attempt to unravel the various functions of MVBs in the cell and their multiple roles in tumor progression. Video Abstract

PurposeSorafenib is a multi-kinase inhibitor that is used as a standard treatment for advanced hepatocellular carcinoma (HCC). However, the mechanism of sorafenib resistance in HCC is still unclear. It has been shown that CISD2 expression is related to the progression and poor prognosis of HCC. Here, we show a new role for CISD2 in sorafenib resistance in HCC.MethodsBioinformatic analysis was used to detect the expression of negative regulatory genes of ferroptosis in sorafenib-resistant samples. The concentration gradient method was used to establish sorafenib-resistant HCC cells. Western blot was used to detect the protein expression of CISD2, LC3, ERK, PI3K, AKT, mTOR, and Beclin1 in HCC samples. Quantitative real-time PCR (qPCR) was used to detect gene expression. CISD2 shRNA and Beclin1 shRNA were transfected to knock down the expression of the corresponding genes. Cell viability was detected by a CCK-8 assay. ROS were detected by DCFH-DA staining, and MDA and GSH were detected with a Lipid Peroxidation MDA Assay Kit and Micro Reduced Glutathione (GSH) Assay Kit, respectively. Flow cytometry was used to detect apoptosis and the levels of ROS and iron ions.ResultsCISD2 was highly expressed in HCC cells compared with normal cells and was associated with poor prognosis in patients. Knockdown of CISD2 promoted a decrease in the viability of drug-resistant HCC cells. CISD2 knockdown promoted sorafenib-induced ferroptosis in resistant HCC cells. The levels of ROS, MDA, and iron ions increased, but the change in GSH was not obvious. Knockdown of CISD2 promoted uncontrolled autophagy in resistant HCC cells. Inhibition of autophagy attenuated CISD2 knockdown-induced ferroptosis. The autophagy promoted by CISD2 knockdown was related to Beclin1. When CISD2 and Beclin1 were inhibited, the effect on ferroptosis was correspondingly weakened.ConclusionInhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant HCC.

Abstract Background Emerging evidence indicates that tumor cells release a large amount of exosomes loaded with cargos during tumorigenesis. Exosome secretion is a multi-step process regulated by certain related molecules. Long non-coding RNAs (lncRNAs) play an important role in hepatocellular carcinoma (HCC) progression. However, the role of lncRNA HOTAIR in regulating exosome secretion in HCC cells remains unclear. Methods We analyzed the relationship between HOTAIR expression and exosome secretion-related genes using gene set enrichment analysis (GSEA). Nanoparticle tracking analysis was performed to validate the effect of HOTAIR on exosome secretion. The transport of multivesicular bodies (MVBs) after overexpression of HOTAIR was detected by transmission electron microscopy and confocal microscopy analysis of cluster determinant 63 (CD63) with synaptosome associated protein 23 (SNAP23). The mechanism of HOTAIR’s regulation of Ras-related protein Rab-35 (RAB35), vesicle associated membrane protein 3 (VAMP3), and SNAP23 was assessed using confocal co-localization analysis, phosphorylation assays, and rescue experiments. Results We found an enrichment of exosome secretion-related genes in the HOTAIR high expression group. HOTAIR promoted the release of exosomes by inducing MVB transport to the plasma membrane. HOTAIR regulated RAB35 expression and localization, which controlled the docking process. Moreover, HOTAIR facilitated the final step of fusion by influencing VAMP3 and SNAP23 colocalization. In addition, we validated that HOTAIR induced the phosphorylation of SNAP23 via mammalian target of rapamycin (mTOR) signaling. Conclusion Our study demonstrated a novel function of lncRNA HOTAIR in promoting exosome secretion from HCC cells and provided a new understanding of lncRNAs in tumor cell biology.

Purpose. Red blood cell distribution width (RDW) has been regarded as an emerging biomarker of the general population and cardiovascular disease. In this study, we aimed to evaluate the association between RDW and diabetic retinopathy (DR). Methods. This case-control study included 167 patients with DR, 131 patients with diabetes mellitus (DM), and 170 age- and sex-matched healthy controls from April 2014 to May 2019. Demographic data, laboratory parameters, and ocular examinations were collected. Results. RDW values of the DR group were significantly higher than those of the healthy control (p

Abstract Background Hypoxia-inducible factor 1α (HIF-1α) is essential in hepatocellular carcinoma (HCC) glycolysis and progression. Yes-associated protein (YAP) is a powerful regulator and is overexpressed in many cancers, including HCC. The regulatory mechanism of YAP and HIF-1α in HCC glycolysis is unknown. Methods We detected YAP expression in 54 matched HCC tissues and the adjacent noncancerous tissues. The relationship between YAP mRNA expression and that of HIF-1α was analyzed using The Cancer Genome Atlas HCC tissue data. We cultured HepG2 and Huh7 HCC cells under normoxic (20% O2) and hypoxic (1% O2) conditions, and measured the lactate and glucose levels, migration and invasive capability, and the molecular mechanism of HCC cell glycolysis and progression. Results In this study, we detected YAP expression in 54 matched HCC tissues and the adjacent noncancerous tissues. We observed that hypoxia-induced YAP activation is crucial for accelerating HCC cell glycolysis. Hypoxia inhibited the Hippo signaling pathway and promoted YAP nuclear localization, and decreased phosphorylated YAP expression in HCC cells. YAP knockdown inhibited HCC cell glycolysis under hypoxic. Mechanistically, hypoxic stress in the HCC cells promoted YAP binding to HIF-1α in the nucleus and sustained HIF-1α protein stability to bind to PKM2 gene and directly activates PKM2 transcription to accelerate glycolysis. Conclusions Our findings describe a new regulatory mechanism of hypoxia-mediated HCC metabolism, and YAP might be a promising therapeutic target in HCC.

Abstract In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to maintain their growth and survival, even under normoxic conditions. Such tumor cell metabolic reprogramming is regulated by factors such as hypoxia and the tumor microenvironment. In addition, dysregulation of certain signaling pathways also contributes to cancer metabolic reprogramming. Among them, the Hippo signaling pathway is a highly conserved tumor suppressor pathway. The core oncosuppressive kinase cascade of Hippo pathway inhibits the nuclear transcriptional co-activators YAP and TAZ, which are the downstream effectors of Hippo pathway and oncogenic factors in many solid cancers. YAP/TAZ function as key nodes of multiple signaling pathways and play multiple regulatory roles in cancer cells. However, their roles in cancer metabolic reprograming are less clear. In the present review, we examine progress in research into the regulatory mechanisms of YAP/TAZ on glucose metabolism, fatty acid metabolism, mevalonate metabolism, and glutamine metabolism in cancer cells. Determining the roles of YAP/TAZ in tumor energy metabolism, particularly in relation to the tumor microenvironment, will provide new strategies and targets for the selective therapy of metabolism-related cancers.

The success of targeted drug therapy for cancer patients has attracted extensive attention from academia and society. However, the rapid development of acquired drug resistance is becoming a major challenge. Autophagy, as an essential homeostatic and catabolic process, is crucial for the degradation or recycling of proteins and cellular components. Autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor–stroma interactions, and resistance to cancer therapy. A growing body of evidence shows that in multiple types of cancer, autophagy is also a key regulator in the tumor microenvironment and the cellular drug response. However, our understanding of the process of autophagy remains incompletely. In this review, we identify the role of autophagy and describe recent advances in the identification of the mechanism by which autophagy is implicated in drug resistance, with a focus on the mode of action, and validation as potential therapeutics.

Abstract Background Autophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. However, the connection between autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays an important role in lactic acid transport and H+ clearance in cancer cells, and Wnt/β-catenin signaling can increase cancer cell glycolysis. We investigated whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by activating the Wnt/β-catenin signaling pathway, accompanied by MCT1 upregulation. Methods Autophagic activity was evaluated using western blotting, immunoblotting, and transmission electron microscopy. The underlying mechanisms of autophagy activation on HCC cell glycolysis were studied via western blotting, and Transwell, lactate, and glucose assays. MCT1 expression was detected using quantitative reverse transcription–PCR (real-time PCR), western blotting, and immunostaining of HCC tissues and the paired adjacent tissues. Results Autophagy promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/β-catenin signaling pathway activation mediated the effect of autophagy on HCC cell glycolysis. β-Catenin downregulation inhibited the autophagy-induced glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was highly expressed in HCC tissues, and high MCT1 expression correlated positively with the expression of microtubule-associated protein light chain 3 (LC3). Conclusion Activation of autophagy can promote metastasis and glycolysis in HCC cells, and autophagy induces MCT1 expression by activating Wnt/β-catenin signaling. Our study describes the connection between autophagy and glucose metabolism in HCC cells and may provide a potential therapeutic target for HCC treatment.

Fengyun-4A (FY-4A) is the first satellite of the Chinese second-generation geostationary orbit meteorological satellites (FY-4). The Advanced Geostationary Radiation Imager (AGRI), onboard FY-4A does not load with high-precision calibration facility in visible and near infrared (VNIR) channel. As a consequence, it is necessary to comprehensively evaluate its radiometric performance and quantitatively describe the attenuation while using its VNIR data. In this paper, the radiometric performance at VNIR channels of FY-4A/AGRI is evaluated based on Aqua/MODIS data using the deep convective cloud (DCC) target. In order to reduce the influence of view angle and spectral response difference, the bi-directional reflectance distribution function (BRDF) correction and spectral matching have been performed. The evaluation result shows the radiometric performance of FY-4A/AGRI: (1) is less stable and with obvious fluctuations; (2) has a lower radiation level because of 24.99% lower compared with Aqua/MODIS; 3) has a high attenuation with 9.11% total attenuation over 2 years and 4.0% average annual attenuation rate. After the evaluation, relative radiometric normalization between AGRI and MODIS in VNIR channel is performed and the procedure is proved effective. This paper proposed a more reliable reference for the quantitative applications of FY-4A data.