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Abstract Background Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. Methods In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. Results Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. Conclusions Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.

The movement of glaciers plays a crucial role in environmental and geological processes, significantly influencing the formation and dynamics of ice bodies. This study leverages feature tracking technology to analyze optical and Synthetic Aperture Radar (SAR) remote sensing imagery, specifically GF-1 optical images and GF-3, Sentinel-1 SAR images, captured during the 2020 to 2021 ablation season in Gongar. The aim was to quantify glacier surface velocities and to evaluate the comparative effectiveness of different remote sensing modalities in capturing these dynamics. Our findings indicate a strong consistency in the spatial distribution of glacier surface velocities derived from diverse remote sensing data sources, with high-precision optical imagery (GF-1) yielding the most accurate velocity measurements, followed by Sentinel-1 SAR data. Notably, large glaciers in Gongar exhibited rapid movements, with an average velocity of 0.16 m/d, primarily at elevations between 4,500 and 6,500 m. The fastest velocities were recorded at approximately 4,500 m elevation. Glaciers with inclines ranging from 10° to 60° displayed the highest velocities within the 20°–30° slope range. It was observed that glaciers on the southeast slope moved faster, exhibiting the highest average surface velocity, in contrast to those on the west slope, which moved more slowly. The surface velocity of the ice tongue region of Krayaylak Glacier that the largest glacier in Pamir, was observed to be lower than 0.6 m/d, indicating a slow movement speed. The study also reveals that the effectiveness of different remote sensing data in detecting glacier velocity in Gongar, with high-resolution data more accurately capturing surface velocities in melting areas or those with slower movement. This study underscores the importance of multi-source remote sensing data in understanding glacier dynamics and contributes valuable insights into the mechanisms driving glacier movements.

Acidic bacterial biofilms-associated enamel white spot lesions (WSLs) are one of the hallmarks of early caries, causing demineralization and decomposition of dental hard tissues. Therefore, to effectively prevent and treat WSLs, it is important to inhibit the activity of cariogenic bacteria while promoting the remineralization of demineralized enamel. Amorphous calcium phosphate (ACP) favors hard tissue remineralization due to its biological activity and ability to release large amounts of Ca2+ and PO43-. However, ACP-based biomineralization technology is not effective due to its lack of antimicrobial properties. Here, carboxymethyl chitosan (CMCS) was employed as a reducing agent and stabilizer, and dual-functional nanohybrids CMCS/AuNPs/ACP with biofilm resistance and mineralization properties were successfully synthesized. The addition of AuNPs enhances the antimicrobial activity and participates in regulating the formation of hydroxyapatite (HAp). The nanohybrids exhibited significant destructive effects against cariogenic bacteria and their biofilms and showed bactericidal activity under bacteria-induced acidic conditions. More importantly, this nanohybrids showed superior results in promoting the remineralization of demineralized enamel, compared to fluoride and CMCS/ACP in vitro. The CMCS/AuNPs/ACP nanohybrids not only reverse the cariogenic microenvironment at the microbial level, but also promote self-repairing of enamel WSLs regarding the microstructure. The present work offers a theoretical and experimental basis for using the CMCS/AuNPs/ACP nanohybrids as a potential dual-functional agent for the clinical treatment of enamel WSLs.

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines.

Background Given its progressive deterioration in the clinical course, noninvasive assessment and risk stratification for the severity of renal fibrosis in chronic kidney disease (CKD) are required. We aimed to develop and validate an end-to-end multilayer perceptron (MLP) model for assessing renal fibrosis in CKD patients based on real-time two-dimensional shear wave elastography (2D-SWE) and clinical variables.Methods From April 2019 to December 2021, a total of 162 patients with CKD who underwent a kidney biopsy and 2D-SWE examination were included in this single-center, cross-sectional, and prospective clinical study. 2D-SWE was performed to measure the right renal cortex stiffness, and the corresponding elastic values were recorded. Patients were categorized into two groups according to their histopathological results: mild and moderate-severe renal fibrosis. The patients were randomly divided into a training cohort (n = 114) or a test cohort (n = 48). The MLP classifier using a machine learning algorithm was used to construct a diagnostic model incorporating elastic values with clinical features. Discrimination, calibration, and clinical utility were used to appraise the performance of the established MLP model in the training and test sets, respectively.Results The developed MLP model demonstrated good calibration and discrimination in both the training [area under the receiver operating characteristic curve (AUC) = 0.93; 95% confidence interval (CI) = 0.88 to 0.98] and test cohorts [AUC = 0.86; 95% CI = 0.75 to 0.97]. A decision curve analysis and a clinical impact curve also showed that the MLP model had a positive clinical impact and relatively few negative effects.Conclusions The proposed MLP model exhibited the satisfactory performance in identifying the individualized risk of moderate-severe renal fibrosis in patients with CKD, which is potentially helpful for clinical management and treatment decision-making.

Abstract Background The incidence of pediatric inflammatory bowel disease (PIBD) has been steadily increasing globally. Delayed diagnosis of PIBD increases the risk of complications and contributes to growth retardation. To improve long-term outcomes, there is a pressing need to identify novel markers for early diagnosis of PIBD. Methods The candidate biomarkers for PIBD were identified from the GSE117993 dataset by two machine learning algorithms, namely LASSO and mSVM-RFE, and externally validated in the GSE126124 dataset and our PIBD cohort. The role of ficolin-1 (FCN1) in PIBD and its association with macrophage infiltration was investigated using the CIBERSORT method and enrichment analysis of the single-cell dataset GSE121380, and further validated using immunoblotting, qRT-PCR, and immunostaining in colon biopsies from PIBD patients, a juvenile murine DSS-induced colitis model, and THP-1-derived macrophages. Results FCN1 showed great diagnostic performance for PIBD in an independent clinical cohort with the AUC of 0.986. FCN1 expression was upregulated in both colorectal biopsies and blood samples from PIBD patients. Functionally, FCN1 was associated with immune-related processes in the colonic mucosa of PIBD patients, and correlated with increased proinflammatory M1 macrophage infiltration. Furthermore, single-cell transcriptome analysis and immunostaining revealed that FCN1 was almost exclusively expressed in macrophages infiltrating the colonic mucosa of PIBD patients, and these FCN1+ macrophages were related to hyper-inflammation. Notably, proinflammatory M1 macrophages derived from THP-1 expressed high levels of FCN1 and IL-1β, and FCN1 overexpression in THP-1-derived macrophages strongly promoted LPS-induced activation of the proinflammatory cytokine IL-1β via the NLRP3-caspase-1 axis. Conclusions FCN1 is a novel and promising diagnostic biomarker for PIBD. FCN1+ macrophages enriched in the colonic mucosa of PIBD exhibit proinflammatory phenotypes, and FCN1 promotes IL-1β maturation in macrophages via the NLRP3-caspase-1 axis.

The conventional laser triangulation displacement sensor (LTDS) is difficult to achieve large dynamic range and high precision measurement simultaneously, since LTDS is affected by factors such as limited detector size, nonlinear input and output variables, laser power fluctuation, speckle noise, electronic noise, etc. Given the above background, we proposed a modified LTDS using a diffraction grating to improve the dynamic range and precision simultaneously. Different from the conventional LTDS, the modified LTDS generates more than one spots on the image sensor, thereby the displacements with different ranges can be obtained from the multiple order diffraction spots. Ultimately, the dynamic range and measurement accuracy will be improved simultaneously by integrating these displacements. In this paper, the principle of the modified LTDS for large dynamic range and high precision measurement is described in detail, and we verified the validity and effectiveness of this idea through the experiment. Compared with the traditional LTDS, the experimental results show that the linearity of the modified LTDS is improved by a factor of 1.5685 and the dynamic range is improved 1.2986 times as well as maintaining the same linearity.

The Tarim River Basin, China’s largest inland river basin, is renowned for its ecological fragility characterized by concurrent greening and desertification processes. Soil wind erosion emerges as a critical factor impacting the natural ecosystem of this region. This study employs a soil wind erosion model tailored to cultivated land, grassland, and desert terrains to analyze the multitemporal characteristics of and spatial variations in soil wind erosion across nine subbasins within the Tarim River Basin, utilizing observed data from 2010, 2015, and 2018. Additionally, this study investigates the influence of various factors, particularly wind speed, on the soil wind erosion dynamics. Following established standards of soil erosion classification, the intensity levels of soil erosion are assessed for each calculation grid within the study area alongside an analysis of the environmental factors influencing soil erosion. Findings indicate that approximately 38.79% of the total study area experiences soil wind erosion, with the Qarqan River Basin exhibiting the highest erosion modulus and the Aksu River Basin registering the lowest. Light and moderate erosion predominates in the Tarim River Basin, with an overall decreasing trend observed over the study period. Notably, the Qiemo River Basin, Dina River Basin, and Kaidu Kongque River Basin display relatively higher proportions of eroded area compared to their total subbasin area. Furthermore, this study underscores the substantial influence of the annual average wind speed on soil erosion within the study area, advocating for prioritizing soil and water conservation programs, particularly in the downstream regions of the Tarim River Basin, to mitigate future environmental degradation.

Abstract Migration and invasion inhibitory protein (MIIP) has been identified as a tumor suppressor in various cancer types. Although MIIP is reported to exert tumor suppressive functions by repressing proliferation and metastasis of cancer cells, the detailed mechanism is poorly understood. In the present study, we found MIIP is a favorable indicator of prognosis in triple-negative breast cancer. MIIP could inhibit tumor angiogenesis, proliferation, and metastasis of triple-negative breast cancer cells in vivo and in vitro. Mechanistically, MIIP directly interacted with ITGB3 and suppressed its downstream signaling. As a result, β-catenin was reduced due to elevated ubiquitin-mediated degradation, leading to downregulated VEGFA production and epithelial mesenchymal transition. More importantly, we found RGD motif is essential for MIIP binding with ITGB3 and executing efficient tumor-suppressing effect. Our findings unravel a novel mechanism by which MIIP suppresses tumorigenesis in triple-negative breast cancer, and MIIP is thus a promising molecular biomarker or therapeutic target for the disease.

IntroductionThe incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteria Pediococcus pentosaceus (P. pentosaceus) can interfere with intestinal immunity, but it is still unknown whether it can alleviate PIBD and the concrete mechanism of immune regulation is unclear.MethodsFor this study, 3-week-old juvenile mice were selected for modeling the development of PIBD. The mice treated with 2% DSS were randomly divided into two groups, which were given P. pentosaceus CECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism exploration in vivo. THP-1 and NCM460 cells were used to investigate the effects of P. pentosaceus CECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalk in vitro.ResultsP. pentosaceus CECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically, P. pentosaceus CECT8330 could inhibit intestinal epithelial apoptosis by suppressing the NF-κB signaling pathway. Meanwhile, it reprogramed macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, leading to a decreased secretion of IL-1β which contributes to the reduction in ROS production and epithelial apoptosis. Additionally, the 16S rRNA sequence analysis revealed that P. pentosaceus CECT8330 could recover the balance of gut microbiota, and a significantly increased content of Akkermansia muciniphila was particularly observed.ConclusionP. pentosaceus CECT8330 shifts macrophage polarization toward an anti-inflammatory M2 phenotype. The decreased production of IL-1β leads to a reduction in ROS, NF-κB activation, and apoptosis in the intestinal epithelium, all of which help to repair the intestinal barrier and adjust gut microbiota in juvenile colitis mice.

Abstract Background Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. Results Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. Conclusions This work provides a new paradigm for the treatment of residual HCC after IRFA. Graphical Abstract

IntroductionSargassum fusiform is considered a traditional Chinese medicinal herb to treat many diseases, Sargassum fusiform polysaccharides (SFPS) were found to display many important biological activities. The purpose of this study was to investigate the in vitro antioxidant activity of crude polysaccharide from Sargassum fusiforme and its protective effect against H2O2-induced injury in LO2 cells.MethodsSFPS was extracted from Sargassum fusiforme using water extraction and alcohol precipitation. High-performance liquid chromatography (HPLC) was used to measure its monosaccharide composition. The in vitro antioxidant activity of SFPS was evaluated using scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical assays. Moreover, its hepatoprotective activity was examined by establishing H2O2-induced LO2 cells injury model.Results and discussionThe results showed that the SFPS was composed of Glc, Ara, Fuc, Gal, Man, Rha and Xyl. Meanwhile, SFPS exhibited strong antioxidant activity and potential hepatoprotective effect. Further studies found that SFPS could alleviate LO2 cells injury induced by H2O2 via decreasing malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, increasing superoxide dismutase (SOD) and catalase (CAT) activities and inhibiting intracellular reactive oxygen species (ROS) production. These results revealed that SFPS had the ability to protect the liver cells from H2O2-induced liver injury through its antioxidant activity.

Coal-gas outburst is the one of most serious coal mine dynamic disasters which affects safety mining, with 39 deaths reported during 2019 in China. The mechanism of coal-gas outbursts is complex, and the prediction methods are immature at present. This article was based on previous research results. Firstly, the occurrence mechanism of coal-gas outburst disasters was summarized. It is clear that the occurrence of coal-gas outburst disasters is jointly affected based on the stability of the static structure of coal-rock, the gas parameters, and the release intensity of shock stress. Secondly, the stability evaluation models of coal-rock static structure, gas parameters, and shock stress release intensity were built, respectively, based on the influence factors. Then they were coupled and supposed to form a new prediction model. Finally, the prediction method was applied to the Ji15-17200 working face of No.12 coal mine in Pingmei company. The working face was divided into three danger levels including weak outburst danger area, medium outburst danger area, and strong outburst danger area. The accuracy of the predicted results was analyzed based on the actual mining condition of the Ji15-17200 working face. The results show that prediction accuracy is high, and it can be used for actual applications. The research results are of guiding significance to better prevent and control coal-gas outburst accidents and ensure safe production in coal mines.

Abstract Expression of endoplasmic reticulum (ER) stress-associated genes is often dysregulated in cancer progression. ER protein 29 (ERp29) is abnormally expressed in many neoplasms and plays an important role in tumorigenesis. Here, we showed ERp29 is a novel target for microRNA-135a-5p (miR-135a-5p) to inhibit the progression of colorectal cancer (CRC); correspondingly, ERp29 acts as an oncoprotein in CRC by promoting proliferation and metastasis of CRC cells, and suppressing apoptosis of the cells. More importantly, we found that miR-135a-5p expression is reversely upregulated by ERp29 through suppressing IL-1β-elicited methylation of miR-135a-5p promoter region, a process for enterocyte to maintain a balance between miR-135a-5p and ERp29 but dysregulated in CRC. Our study reveals a novel feedback regulation loop between miR-135a-5p and ERp29 that is critical for maintaining appropriate level of each of them, but partially imbalanced in CRC, resulting in abnormal expression of miR-135a-5p and ERp29, which further accelerates CRC progression. We provide supporting evidence for ERp29 and miR-135a-5p as potential biomarkers for diagnosis and treatment of CRC.

Calcium-dependent protein kinases (CDPKs) are important in calcium influx, triggering several biological processes in Cryptosporidium spp. As they are not present in mammals, CDPKs are considered promising drug targets. Recent studies have characterized CpCDPK1, CpCDPK3, CpCDPK4, CpCDPK5, CpCDPK6, and CpCDPK9, but the role of CpCPK2A remains unclear. In this work, we expressed recombinant CpCDPK2A encoded by the cgd2_1060 gene in Escherichia coli and characterized the biologic functions of CpCDPK2A using qRT-PCR, immunofluorescence microscopy, immuno-electron microscopy, and in vitro neutralization. The results revealed that CpCDPK2A protein was highly expressed in the apical region of sporozoites and merozoites and in macrogamonts. Monoclonal or polyclonal antibodies against CpCDPK2A failed to block the invasion of host cells. Among the 44 candidate inhibitors from molecular docking of CpCDPK2A, one inhibitor was identified as having a potential effect on both Cryptosporidium parvum growth and CpCDPK2A enzyme activities. These data suggest that CpCDPK2A may play some roles during the development of C. parvum and might be a potential drug target against cryptosporidiosis.

Fluid mobility (i.e., permeability to viscosity ratio) is a key parameter that can evaluate the reservoir permeability and delineate the fluid characteristic in hydrocarbon-saturated reservoirs. Based on the asymptotic representation for the frequency-dependent reflections in the fluid-saturated pore-elastic media and frequency-dependent AVO inversion, we propose a novel method for estimating fluid mobility from poststack seismic data. First, we establish the relationship between fluid mobility and frequency-dependent AVO analysis. Then, the fluid mobility is estimated using the theory of frequency-dependent AVO inversion. Tests on synthetic data reveal that the fluid mobility shows excellent imageability for the fluid-saturated reservoirs and can accurately delineate the spatial distribution shape of the gas-saturated reservoir. The application of field data examples demonstrates that the fluid mobility calculated by the proposed method produces less background interferences caused by elastic layers compared with the conventional frequency-dependent fluid indicator. The frequency-dependent fluid mobility takes into account the dispersion features associated with hydrocarbon reservoirs, and it provides a new way to detect the location of hydrocarbon reservoirs and characterize their spatial distribution.

Fucoidan has many biological functions, including anti-tumor activity. Additionally, it has been suggested that low-molecular-weight fucoidans have greater bioactivities. This study aimed to examine the degradation, purification, physicochemical characterization and in vitro antitumor activity of fucoidan from Sargassum hemiphyllum (Turner) C. Agardh. Fucoidan was isolated using DEAE-cellulose-52 (F1, F2), Vc-H2O2 degration, and Sepharose CL-6B gel (DF1, DF2) from crude Sargassum fucoidans. Physicochemical characteristics of four isolated fucoidans were examined using chemical and monosaccharide composition, average molecular weight (Mw), and FTIR. Furthermore, the anti-proliferative effects of purified fucoidans on human hepatocellular carcinoma cells (HepG2), human Burkitt Lymphoma cells (MCF-7), human uterine carcinoma cells (Hela) and human lung cancer cells (A549) were analyzed by MTT method. The apoptosis of HepG2 cells was detected by flow cytometry. Our data suggest that the contents of polysaccharide, L-fucose and sulfate of DF2 were the highest, which were 73.93%, 23.02% and 29.88%, respectively. DF1 has the smallest molecular weight (14,893 Da) followed by DF2 (21,292 Da). The four fractions are mainly composed of fucose, mannose and rhamnose, and the infrared spectra are similar, all of which contain polysaccharide and sulfate characteristic absorption peaks. The results of MTT assay showed that the four fractions had inhibitory effects on HepG2 and A549 in the range of 0.5–8 mg/mL, and the four fractions had strong cytotoxic effects on HepG2 cells. DF2 had the best inhibitory effect on HepG2 (IC50 = 2.2 mg/mL). In general, the antitumor activity of Sargassum fucoidans is related to the content of L-fucose, sulfate and molecular weight, and Sargassum fucoidan has the best inhibitory effect on HepG2 hepatocellular carcinoma cells. Furthermore, when compared to MCF-7, Hela, and A549 cells, Sargassum fucoidans had the best capacity to reduce the viability of human hepatocellular carcinoma cells (HepG2) and to induce cell apoptosis, proving itself to have a good potential in anti-liver cancer therapy.

The corresponding engineering effects are inevitable and occurred when the coal mines working face mining. The main manifestations are distribution of mining stress and fracture of overlying rock seams. The mining effects play a controlling role in the occurrence of dynamic disasters such as disastrous coal mine earthquakes and rock bursts. In view of this, taking No. 1305 working face mining of Dongtan coal mine for background, the distribution and transfer characteristics of mining stress in working face and fracture characteristics of roof rock formation were studied by theoretical analysis, numerical simulation, and microseismic monitoring. The change mechanism of stress, strain, strain rate, and energy of rock mass in the process of coal mine earthquake gestation was expounded by the Burgers mechanical model. The results show that the microseismic hypocenters are mainly concentrated near the increasing pressure zone and the fractured zone. The hypocenter first gathered at the main roof, and then, it gradually developed upward and returns to the main roof after mining. The distribution of microseismic frequency and advanced support pressure is basically consistent. The microseismic energy peak value area with respect to the support pressure peak value area often presented a certain lag. The relationship of empirical formula is inferred as YE=ME+∆d. The overlaying rock caving zone and fractured zone with height of 37.8 m and 95 m, respectively, were revealed by microseismic monitoring. It is 8.4% larger than the numerical result. It shows that the prediction results of overlying rock fracture height based on the distribution of large energy hypocenter points is well applied in the field, and the operations are simple and intuitive.

Purpose: To investigate the effect of primary varicocele and related surgery in male infertility through meta-analysis.Methods: A systematic search of the literature was conducted using the Medline, Embase, Cochrane, and CNKI databases. The search was up to September 2019. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using RevMan 5.2. A random-effects model was used to calculate the overall combined risk estimates.Results: After screening 687 articles, 4 randomized controlled trials with 349 patients were included. One hundred seventy two patients were addressed in embolization/ligation, with 177 patient's observation treatment. The number of spontaneous pregnancies in the two groups was 41 and 40, respectively. There was no significant difference in pregnancy rate between the operation group and the control group. RR = 1.05 [0.72, 1.54].Conclusion: There is not enough evidence to explain the surgical treatment of varicocele can improve the natural fertility of the infertile couples, and there is still a need for most of prospective randomized controlled trials to verify the efficacy of varicocele surgery for treating of male infertility. We do not deny the importance of this operation, we just want to call on everyone to strictly grasp the indications of the operation, avoid ineffective medical expenses, and avoid unnecessary pain to patients.

In the present study, a selenium-chondroitin sulfate (SeCS) was synthesized by the sodium selenite (Na2SeO3) and ascorbic acid (Vc) redox reaction using chondroitin sulfate derived from shark cartilage as a template, and characterized by SEM, SEM-EDS, FTIR and XRD. Meanwhile, its stability was investigated at different conditions of pH and temperatures. Besides, its antioxidant activity was further determined by the DPPH and ABTS assays. The results showed the SeCS with the smallest particle size of 131.3 ± 4.4 nm and selenium content of 33.18% was obtained under the optimal condition (CS concentration of 0.1 mg/mL, mass ratio of Na2SeO3 to Vc of 1:8, the reaction time of 3 h, and the reaction temperature of 25 °C). SEM image showed the SeCS was an individual and spherical nanostructure and its structure was evidenced by FTIR and XRD. Meanwhile, SeCS remained stable at an alkaline pH and possessed good storage stability at 4 °C for 28 days. The results on scavenging free radical levels showed that SeCS exhibited significantly higher antioxidant activity than SeNPs and CS, indicating that SeCS had a potential antioxidant effect.

Abstract Previous studies have reported that the aberrantly expressed AKR1B10 is associated with many cancer development, however the functional roles of AKR1B10 and its regulatory mechanisms in hepatocellular carcinoma (HCC) have been limited studied. In this project, we identified AKR1B10 functional as an oncogene in HCC through tumor/normal human tissue comparison from both GEO microarray and TCGA RNAseq dataset. Further experimental validations from three HCC cell lines (SMMC-7721, HePG2 and HeP3B) also suggested the ontogenetic functions of AKR1B10 in HCC tumor growth. By knocking down AKR1B10 through shRNA in HCC HeP3B cells, we showed it significantly induced cell cycle arrest and inhibited cell growth. Interestingly, integrative analysis of TCGA RNAseq data and miRNA-seq data predicted that miR-383-5p, a novel post-transcriptional tumor suppressor, is negatively associated with AKR1B10 expression. To further investigate the role of miR-383-5p in regulating AKR1B10 in HCC, we performed Dual-luciferase reporter assay experiments. Results showed that miR-383-5p is an upstream modulator targeting AKR1B10 in the post-transcriptional stage. Thus, we report AKR1B10 modulated regulated by miR-383-5p, promotes HCC tumor progress, and could be potentially a therapeutic target for precision medicine in HCC.

Abstract Background Breast cancer is one of the most frequent malignancies and the second leading cause of cancer-related mortality in women. MicroRNAs play a key role in breast cancer development and progression. microRNA(miR)-8084 has been observed an aberrant expression in breast cancer. However, the functions and regulatory axes of miR-8084, particularly in breast cancer, were not entirely clear. Methods miR-8084 expression in breast cancer were investigated in a GEO dataset by in silico analysis and in 42 paired tumor tissues by qPCR. The effects of deregulation of miR-8084 on breast cancer cell proliferation, migration and invasion in vitro and tumorigenicity in vivo were examined by colony-formation assay, wound healing assay, transwell assay and nude mouse subcutaneous tumor formation model. The target gene of miR-8084 were predicted by TargetScan and miRDB, and confirmed by luciferase reporter system. The roles of miR-8084 in the breast cancer cell proliferation, apoptosis and epithelial–mesenchymal transition (EMT) were investigated by MTS, FACS and associated-marker detection by western blot. Results miR-8084 is significantly up-regulated in both serum and malignant tissues from the source of breast cancer patients. miR-8084 promotes the proliferation of breast cancer cells by activating ERK1/2 and AKT. Meanwhile miR-8084 inhibits apoptosis by decreasing p53-BAX related pathway. miR-8084 also enhances migration and invasion by inducing EMT. Moreover, the tumor suppressor ING2 is a potential target of miR-8084, and miR-8084 regulatory axes contribute to pro-tumor effect, at least partially through regulating ING2. Conclusion Our results strongly suggest that miR-8084 functions as an oncogene that promotes the development and progression of breast cancer, and miR-8084 is a potential new diagnostic marker and therapeutic target of breast cancer.

Abstract Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro. Subcutaneous xenografts and pulmonary metastases models were constructed in nude mice to compare the differences in tumorgenesis and metastasis after Knockdown of PKM2. Our results obtained from in vitro cell biological behavior, in vivo tumorigenicity studies, and primary GC samples revealed an oncogenic role for PKM2 in GC. Furthermore, for those GC patients who received radical resection, PKM2 might serve as a novel prognostic biomarker and target which would allow for a brand new treatment strategy for GC in the clinical settings.

Seismic low-frequency component included more fluid information, which was still a focus in geophysics. Seismic pre-stack data contained more fluid information, but signal to noise ratio (SNR) was low. By comparison, seismic post-stack data had a high SNR, but some fluid information was lost during data processing. Different angel stacks reflected different fluid seismic amplitude, compared with near-angle stacks. Far angle stacks had more low frequency components, which were more benefit for fluid identification. Based on this principle, combined with the pre-stacks and post-stacks seismic data, more fluid information would be included. In this study, a new fluid identification method was proposed. This method combined the post-stack seismic and pre-stack seismic data, it took into consideration high SNR of the post-stack seismic data and the large fluid amplitude differences of the pre-stack different angles. Field testing indicated this method was quite effective in detecting fluids. Keywords: Fluid identification, Seismic low-frequency, Signal to noise ratio, Post-stack seismic data, Pre-stack seismic data

As a green and preferred technology for energy crisis and environmental issues, continuous research on photocatalysis and gas sensing has come forth at an explosive rate. Thus far, promising synthetic methods have enabled various designs and preparations of semiconductor-based nanostructure which have shown superior activity. This review summarized various synthetic routines toward carbon sphere template derived hollow nanostructures and their successful attempts in synthesize doping, solid solution, heterostructure, and surface modified nanostructures for heterogeneous photocatalysis and gas sensing. Moreover, the challenges and future prospects are briefly discussed. It is eagerly anticipated that this review may broaden the view and in-depth understanding of carbon sphere template derived hollow nanostructures while expected to have further progresses in heterogeneous photocatalysis, gas sensing and other related fields which will make great contributions to their application.

Oil and gas pipeline leakage incidents occur from time to time, causing environmental pollution, property damages and other serious consequences. Flattening the oil and gas pipelines to stop the flow can effectively reduce losses. The extrusion device can quickly arrive at the incident scene and flatten the pipeline within a short time using hydraulic power or mechanical force so as to stop the flow. However, due to the springback problem, a small amount of oil or gas will still leak. Therefore, studying the bending springback of flattened oil and gas pipelines is very essential to solving the oil or gas leakage problem. This paper analyzes the theories related to flattening and closure of oil and gas pipelines. Springback is an inevitable result of the elastic redistribution of the internal stress in a flattened pipeline. Regarding the bending springback problem of flattened steel pipelines, based on the assumptions of plane strain, this paper applies the plate bending theory and establishes a theoretical model for the bending springback process of flattened steel pipelines and obtains the factors affecting the bending springback of flattened pipelines. At the same time, it uses the model in conjunction with the experiment to analyze the relationship between the springback of a flattened pipeline and the closure efficiency.

Objective: To measure oxalate, calcium, and sodium contents of traditional Chinese medicines (TCMs) that are commonly used to prevent and dissolve urinary stones to exclude the possibility that long-term use of such medicines promotes stone formation. The second objective was to measure citrate, potassium, and magnesium contents in the same medicines to provide possible clues about the mechanisms of prevention and dissolution of urinary stones by TCMs. Methods: Ten of the most commonly-used TCMs for preventing and dissolving urinary stones were chosen and subjected to ion chromatography (IC) to measure water-soluble and total oxalate and citrate contents. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to measure calcium, potassium, magnesium, and sodium contents in a water extract and in digestion liquid. Results: Average contents of water-soluble oxalate, calcium, and sodium in the water extract were 41.92, 84.32, and 22.82 mg/100 g, respectively, far below the normal dietary intake of adults in China. The average contents of citrate and magnesium in water extracts were 268.99 and 66.65 mg/100 g, respectively, below the recommended intake for adults. These ion contents are therefore insufficient to inhibit the formation of urinary stones. The average content of potassium in the water extract was 867.71 mg/100 g, which was relatively abundant, so taking the prescription used in this experimental protocol can increase the body's potassium content to some extent. Conclusions: Long-term use of TCMs would not increase the risk of urinary stone formation. The potassium content in TCMs is high, which is one possible reason for the prevention of urinary stones by TCMs.

This study was performed to investigate the quality of fresh wet noodles made from flour milling streams. The basic composition, texture properties, cooking characteristics, and moisture status were measured to evaluate the qualities of noodles. The results indicated that as storage time increased, the springiness of fresh wet noodles gradually decreased, but the hardness increased. Additionally, the cooking loss rate was increased obviously, and the water absorption rate generally decreased. The relaxation times T21 and T22, analyzed by low-field nuclear magnetic resonance, showed a downward trend that proton mobility became poor and bound water changed into intermediate water. Noodles made from reduction flour exhibited better quality. Compared to that with ambient temperature storage, the wet noodles under frozen storage showed better quality. The relaxation time T21, and T22 showed a positive correlation with noodle quality.

SLC7A5, who is also named LAT-1, has been validated as a promoter regulated by miRNA-126 in our previous research for gastric cancer cells. However, the mechanisms driving SLC7A5 to affect the bio-function of gastric cancer cells are unclear, remaining us lots of to elucidate. The aim of this study is to investigate the regulating effect of CRKL, one of the critical genes involving with gastric cancer progression, on SLC7A5 expression. By studying the gastric cancer cell lines and clinical pathological specimens, we found that the expression of SLC7A5 was significantly correlated to CRKL. By depleting CRKL in gastric cancer SGC-7901 cells, the SLC7A5 expression was impaired, and the invasion and migration of SGC-7901 cells were suppressed. Ectopic expression of SLC7A5 could drastically rescue the phenotypes induced by CRKL depletion in this study. Accordingly, we conclude that SLC7A5 functions as a promoter in gastric cancer metastasis, and CRKL could be one of its regulators modulating the expression of SLC7A5 and consequentially affect the metastatic feature of SGC-7901 cells. The findings in this study indicate a regulation relationship between CRKL and SLC7A5, and provide useful evidence for gastric cancer therapeutic strategies.

BACKGROUND:Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is crucial for successful drug development. However, due to immune tolerance, making it difficult to generate antibodies using conventional approaches. METHODOLOGY/FINDINGS:Mixed four human gastric cancer (GC) cell lines were used as the immunogen in A/J mice; sixteen highly positive hybridoma colonies were selected via fluorescence-activated cell sorting-high throughput screening (FACS-HTS) using a total of 20,000 colonies in sixty-seven 96-well plates against live cells (mixed human GC cells versus human PBMC controls). MS17-57 and control commercial Alkaline Phosphatase (ALP) mAbs were used to confirm the target antigens (Ags), which were identified as ALPs expressed on the GC cell surface through a combination of western blot, immunoprecipitation and mass spectrometry (MS). MS identified the Ags recognized by MS17-57 to be two variants of a secreted ALP, PALP and IALP (Placental and intestinal ALP). These proteins belong to a hydrolase enzyme family responsible for removing phosphate groups from many types of molecules. Immunofluorescence staining using MS17-57 demonstrated higher staining of gastrointestinal (GI) cancer tissues compared to normal GI tissues (P

MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.

Iron deficiency anemia is an extra-stomach disease experienced in H. pylori carriers. Individuals with type A blood are more prone to suffering from H. pylori infection than other individuals. To clarify the molecular mechanisms underlying H. pylori-associated anemia, we collected erythrocytes from A, B, O, and AB blood donors and analyzed morphology, the number of erythrocytes with H. pylori colonies attached to them, and iron contents in erythrocytes and H. pylori (NCTC11637 and SS1 strains) by means of optical microscopy, scanning electron microscopy, and synchrotron radiation soft X-ray imaging. The number of type A erythrocytes with H. pylori attached to them was significantly higher than that of other erythrocytes (P

Abstract Background Added sugars intake is common among individuals with Parkinson’s disease (PD), yet the link between added sugars intake and PD is not well understood. Our study aims to investigate the association between added sugars intake and PD. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) from1990 to 2020. Added sugars intake was estimated based on a 24-hour dietary recall from participants. Multivariable logistic regression analysis was employed to explore the relationship between added sugars intake and the prevalence of PD. Restricted cubic spline (RCS) was used to explore the nonlinear association between added sugars intake and PD. To further observe whether the conclusions were consistent across different subgroups, we conducted subgroup analyses to investigate the association of added sugars intake with PD in different populations. Results The study included 12,489 participants, of which 100 had PD. When weighted, the data represented 136,959,144 participants. The study revealed a positive association between added sugars intake and the prevalence of PD. In multivariable regression models adjusted for all confounding factors, compared with the lowest quartile of added sugars intake, the third quartile (OR = 2.99; 95% CI: 1.43–6.26) and those consuming more than 25% of their calories from added sugars (OR = 3.34; 95% CI: 1.03–10.86) had the highest risk of PD. The RCS curve showed an L-shaped nonlinear association between added sugars intake and PD. Two-segment linear regression by sex revealed that PD prevalence in women was linearly related to sugar intake (nonlinear P = 0.465), while men exhibited an L-shaped nonlinear relationship (nonlinear P = 0.03). Additionally, subgroup analysis showed that alcohol consumption and diabetes significantly influenced the association between added sugars intake and the prevalence of PD. Conclusion These results highlight a positive association between added sugars intake and the prevalence of PD, particularly among women, heavy drinkers, and individuals with diabetes.