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Objective The construction of road pile-plate structures can significantly impact adjacent metro tunnels and railway structures. Under stringent regulatory requirements and complex engineering conditions, it is essential to ensure the safety of existing metro and railway structures. Method Based on the new Bai′an Highway project, numerical simulation methods are utilized to construct a Plaxis3D finite element calculation model. This model simulates various construction conditions to analyze the impact of pile-plate structure construction process on the adjacent existing metro and high-speed railway. Result & Conclusion The research results indicate that during the construction of bored cast-in-place piles in this road project, adverse conditions such as hole collapse and soil plug effect are likely to occur. These conditions can negatively impact adjacent metro lines, causing metro tunnel displacement and convergence deformation to exceed control values. In contrast, the construction process has less impact on high-speed railway bridges, with deformation remaining within controllable limits. Therefore, it is necessary to improve and optimize the road construction plan, such as increasing the distance between pile foundation and metro tunnels and extending the length of some piles. A safety assessment of the optimized design scheme is conducted, and subsequent numerical simulation results show that the metro tunnel displacement and deformation caused by road construction can meet the required standards, ensuring metro tunnel structural safety.

Sjögren's syndrome (SS) is a prevalent systemic autoimmune disease, primarily affecting exocrine glands, characterized by lymphocyte and plasma cell infiltration. Patients typically exhibit dry mouth and eyes, with potential involvement of the digestive tract, lungs, and kidneys. In China, SS prevalence ranges from 0.29% to 0.77%, rising to 3.00%-4.00% among the elderly. In Europe, the prevalence is approximately 0.23%. The pathogenesis of SS involves interactions of multiple cells and cytokines, including salivary gland epithelial cells, T-cells, B-cells, dendritic cells, interferon (IFN), interleukin (IL), tumour necrosis factor (TNF) and inflammasomes. Currently, glandular therapy for SS is primarily localised, while treatment for systemic involvement is mainly borrowed from other autoimmune diseases, with no approved targeted drugs yet. Among the targeted therapeutic agents for SS, rituximab, a B-cell targeted therapy, is the most studied and has shown improved salivary efficacy in SS patients with cryoglobulin vasculitis. BAFF inhibitors, CD40 targeting agents, and mesenchymal stem cells have also demonstrated cartain therapeutic effects. For most systemic involvement, glucocorticoids (GCs) are the first-line treatment, while immunosuppressants and biologics serve as second-line options for GCs-tolerant or resistant patients. Although many potential therapeutic targets have been identified, few drugs have been clinically translated. Currently, there is a need to develop relatively safe and effective treatment regimens with minimal adverse effects through comprehensive patient assessment and multidisciplinary collaboration. Future SS drug research will focus on targeted therapies, adverse effects reduction, and multi-drug combinations.

Gastric cancer (GC) has become the first malignant tumor with highest incidence rate and mortality of cancer in China, finding therapeutic targets for gastric cancer is of great significant for improving the survival rate of patients with GC. Recently, many of studies have shown that LncRNAs is involved in multiple biological progresses in the development of GC. This study, we screened for abnormally high expression of LncSHANK3 in GC through the TCGA database, and found that LncSHANK3 sponge adsorbs miR-4530, further competing with MNX1 and binding to miR-4530. We demonstrated the interaction between LncSHANK3 and miR-4530 through luciferase reporting analysis, with miR-4530 negatively regulating MNX1.Through CCK8, colony formation, transwell, and wound healing assays, it was found that LncSHANK3 affects the occurrence of GC through cell proliferation, migration and invasion. In conclusion, LncSHANK3/miR-4530/MNX1 axis is a potential mechanism for the treatment of GC.

Two-hierarchical nanostructures, characterized by two distinct configurations along the height direction, exhibit immense potential for applications in various fields due to their significantly enhanced controllable degree compared to single-order structures. However, due to the limitations imposed by planar technology, the realization of two-hierarchical nanostructures encounters huge challenges. In this work, we developed a one-step etching method based on inductively coupled plasma reactive ion etching for two-hierarchical nanostructures. Thanks to the shrinking effect of the Cr mask and the generation of a passivation layer during etching, the target materials experienced two different states from vertical etching to shrink etching. Consequently, the achieved two-hierarchical nanostructure configuration features a cross-section of an upper triangle and a lower rectangle, showing higher controllable degrees compared to the one-order ones. Both the mask pattern and etching parameters play crucial roles, by which two-hierarchical structures with diversiform shapes can be constructed controllably. This method for two-hierarchical nanostructures offers advantages including excellent control over structural properties, high processing efficiency, uniformity across large areas, and universality in materials. This developed strategy not only presents a simple and rapid nanofabrication platform for realizing optoelectronic devices, but also provides innovative ideas for designing the next generation of high-performance devices.

Because of the high viscosity of severe chain entanglements, a time-consuming process of aligning microstructural orientation in high molecular-weight (Mw) block copolymer photonic crystal films imposed limitations on efficient mass production. In this study, the effective alignment of the block copolymer microstructures in the film state can be carried out within approximately a few minutes. This achievement was realized through the synergistic localized compatibility of dry brush and shear stress during the spin-casting process. The orientation and orderliness of the microphase-separated lamellar structure in as-spun poly(styrene)-block-poly(4-vinylpyridine) (PS-b-P4VP) films can be meticulously controlled by introducing blends with PS homopolymer (hPS) of varying Mws (Mw,hPS) and cholesteric liquid crystal mesogen (Chol). Within the ternary blended films of hPS/PS-b-P4VP(Chol), the wet-brush miscibility by blending low-Mw hPS with a small molecular weight ratio (α) of Mw,hPS to Mw,bPS (Mw of the PS block chain) of α

In order to solve the problem that the crack defects generated on the surface of MEMS devices are difficult to detect under high overload impact, this paper proposes a crack detection method based on attribute weighted naive Bayes improved OTSU algorithm. Based on the analysis of the surface defects in MEMS devices image, the edge information of the crack defect in the image is extracted by image processing such as image detail sharpening, grayscale processing, image enhancement and edge extraction based on Canny operator, and the pseudo crack in the image is removed by the least square method; the attribute weighted naive Bayes algorithm is introduced to improve the traditional OTSU image processing method, the crack defect detection results of the MEMS devices image are obtained, the crack defects are quantitatively characterized, and the length and width of the crack defects are calculated. Comparative experiments were conducted using multiple detection methods, the results showed that the crack detection method proposed in this paper can obtain the crack defect information of MEMS devices efficiently and accurately.

Abstract Background Metastasis and drug resistance of breast cancer have become a barrier to treating patients successfully. Long noncoding RNAs (lncRNAs) are known as vital players in cancer development and progression. Methods The RT-qPCR were used to detect the gene expression. Colony formation assay, would healing assay, and transwell assay were performed to investigate oncogenic functions of cells. CCK8 assay was used to detect the cell viability. Western blot was applied to detect the protein level. Dual-luciferase reporter assay was used to determine the relationship between molecules. Mouse orthotopic xenograft tumor models were established to evaluate the effects of BCAR4 on tumor growth and metastasis in vivo. Results LncRNA BCAR4 was significantly increased in breast cancer patients’ tissues and plasma and upregulated in breast cancer cell lines. BCAR4 upregulation was correlated with the TNM stages and decreased after surgical removal of breast tumors. Silencing of BCAR4 suppressed breast cancer cell colony formation, migration, invasion, and xenograft tumor growth and promoted chemo-sensitivity. Mechanistically, BCAR4 facilitates breast cancer migration and invasion via the miR-644a-CCR7 axis of the MAPK pathway. BCAR4 promotes ABCB1 expression indirectly by binding to and down-regulating miR-644a to induce chemo-resistance in breast cancer. Conclusions Our findings provide insights into the oncogenic role of BCAR4 and implicate BCAR4 as a potential diagnostic biomarker and a promising therapeutic agent to suppress metastasis and inhibit chemo-resistance of breast cancer.

Abstract Background Long non-coding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Abnormally expressed lncRNA can be used as a diagnostic marker for cancer. In this study, we aim to investigate the clinical significance of MIR99AHG expression in lung adenocarcinoma (LUAD), and its biological roles in LUAD progression. Methods The relative expression of MIR99AHG in LUAD tissues and cell lines was analyzed using public databases and RT-qPCR. The biological functions of MIR99AHG were investigated using a loss-of-function approach. The effect of MIR99AHG on lung fibrosis was assessed by scratch assay, invasion assay and lung fibrosis rat model. FISH, luciferase reporter assay and immunofluorescence were performed to elucidate the underlying molecular mechanisms. Results LncRNA MIR99AHG expression level was downregulated in LUAD tissues and cell lines. Low MIR99AHG levels were associated with poorer patient overall survival. Functional analysis showed that MIR99AHG is associated with the LUAD malignant phenotype in vitro and in vivo. Further mechanistic studies showed that, MIR99AHG functions as a competitive endogenous RNA (ceRNA) to antagonize miR-136-5p-mediated ubiquitin specific protease 4 (USP4) degradation, thereby unregulated the expression of angiotensin-converting enzyme 2 (ACE2), a downstream target gene of USP4, which in turn affected alveolar type II epithelial cell fibrosis and epithelial–mesenchymal transition (EMT). In summary, the MIR99AHG/miR-136-5p/USP4/ACE2 signalling axis regulates lung fibrosis and EMT, thus inhibiting LUAD progression. Conclusion This study showed that downregulated MIR99AHG leads to the development of pulmonary fibrosis. Therefore, overexpression of MIR99AHG may provide a new approach to preventing LUAD progression.

Ionic surfactants are easily adsorbed by silt and clay particles, thus affecting the flocculation characteristics and settling behavior. The settling velocity, typical size, Zeta potential and surface tension of silt flocs were measured in the presence of two different kinds of ionic surfactants. The results indicated that the cetyltrimethylammonium bromide (CTAB, a typical cationic surfactant) can dramatically accelerate the settling of slit particles, while the linear alkylbenzene sulfonate (LAS, a typical anionic surfactant) slightly retarded silt sedimentation to some extent. In still water, the representative settling velocity dramatically increased from 0.36 cm s−1 to 0.43 cm s−1 with the increase of CTAB concentration, which increased by more than 20%. Oppositely, the sedimentation rate decreased from 0.36 cm s−1 to 0.33 cm s−1 with the increase of LAS concentration. In flowing water, as the flow rate increased from 0 to 20 cm s−1 and the ionic surfactant concentration increased from 0 to 10 mg L−1, the sedimentation rate decreased to 57% and 89% in the presence of CTAB and LAS respectively, which was due to an enhanced dispersion of silt particles and a breaking of flocs. The SEM image test shows that the floc particle size increased 1.5 times of the primary particle size under the high CTAB concentration. The flocculation induced by ionic surfactants greatly influences the sediment size as well as the law of settling velocity. The intrinsic influence mechanism was also discussed based on the variations of silt particle properties. This systematic study can be used for further development of flocculation models and particle size distribution of fine-grained soil.

In order to explore the nutritional value and active function of Akebia trifoliata pericarp, the main nutritional components contents of protein, fat, total sugar, reducing sugar, 8 mineral elements, total flavonoids, total phenols and total saponins were determined by using Kjeldahl method, acid hydrolysis, phenol sulfuric acid method, 3,5-dinitrosalicylic acid method, ICP-AES method, NaNO2-AlCl3 method, Folin-ciocalten and vanillin-perchloric acid. The antioxidant capacity of pericarp extracts was also evaluated. The results showed that the contents of protein (8.16%±0.11%), reducing sugar (19.31%±0.21%) and total sugar (32.61%±0.18%) in the peel of Akebia trifoliata were high, and the pectin content determined by gravimetric method was (20.08%±0.20%). Among the eight nutrient elements measured, K content was the richest (14061.17 μg/g DW), followed by Ca (4959.28 μg/g DW). The orders of the contents of eight mineral elements were K>Ca>Mg>Fe>Mn>Na>Cu>Zn. The contents of total flavonoids, polyphenolics and saponins were (20.58±0.12), (31.53±0.18) and (45.20±12.04) mg/g DW, respectively. The scavenging capabilities of extraction on the free radicals of DPPH and ABTS+ were also investigated. When the scavenging rate reached to 50%, the IC50 values on DPPH and ABTS+ free radicals scavenging were 0.049, 0.052 mg/mL, respectively. The scavenging ability of extracts in Akebia trifoliata pericarp was dose-dependent. The contents of total flavonoids, total polyphenols and total saponins had strong and positive correlations with antioxidant activity (P

Waldenström Macroglobulinemia (WM) is a rare chronic lymphoproliferative disease, accounting for less than 2% of hematological malignancies. It is characterized by plasma cytoid lymphocyte infiltration in bone marrow and abnormal increase of monoclonal IgM in peripheral blood. Only 5%–10% of cases of WM secrete monoclonal IgG and IgA components or do not secrete monoclonal long immunoglobulin. This case is the first to report of serum protein recombination from lgM and Igkappa band mutation to abnormal lgG and Igkappa band after 6 years of treatment in a male patient with WM.

BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-022-02588-8.

The complex band structure and carrier decay response upon photoexcitation of the chiral semiconductor tellurium remain to be unveiled. Here, the authors report unusual dynamic band modifications in Te near band-edge structure due to photoinduced symmetry breaking and strong anisotropy in carrier decay dynamics.

Abstract Background Foxp3+CD4+ regulatory T cells (Treg) constitutes a key event in autoimmune diseases. STAT5b is the critical link between the IL-2/15 and FOXP3, the master regulator of Treg cells. Methods The CD3+T cell and Foxp3+CD4+ regulatory T cells were overexpressioned or knockdown MKL-1 and STAT5a and tested for Treg cell development and function. Direct interaction of MKL-1 and STAT5a were analyzed by coimmunoprecipitation assays, Luciferase assay, Immunofluoresence Staining and Yeast two-hybrid screening. The effect of MKL-1 and STAT5a on the Treg genes expression was analyzed by qPCR and western blotting and Flow cytometry. Results However, the molecular mechanisms mediating STAT5b-dependent Treg genes expression and Treg cell phenotype and function in autoimmune diseases are not well defined. Here, we report that the MKL-1 is a coactivator for the major Treg genes transcription factor STAT5b, which is required for human Treg cell phenotype and function. The N terminus of STAT5b, which contains a basic coiled-coil protein–protein interaction domain, binds the C-terminal activation domain of MKL-1 and enhances MKL-1 mediated transcriptional activation of Treg-specific, CArG containing promoters, including the Treg-specific genes Foxp3. Suppression of endogenous STAT5b expression by specific small interfering RNA attenuates MKL-1 transcriptional activation in cultured human cells. The STAT5b–MKL-1 interaction identifies a role of Treg-specific gene regulation and regulated mouse Treg cell development and function and suggests a possible mechanism for the protective effects of autoimmune disease Idiopathic Thrombocytopenic Purpura (ITP). Conclusions Our studies demonstrate for the first time that MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function. Video abstract

Purpose: miR-5100 participates in the proliferation of lung cancer and pancreatic cancer cells, and participates in the differentiation of osteoblasts. However, the regulation of gastric cancer cells in gastric cancer cells remains unclear. Experimental design: The blood of patients was collected to detect the expression level of miR-5100, and the apoptosis and autophagy levels of cells were detected using western blot, flow cytometry, and confocal. At the same time, in vitro tumor formation experiments in nude mice were used to verify the results of in vitro experiments. Results: The expression of miR-5100 is related to the prognosis of gastric cancer, miR-5100 can enhance the apoptosis level of gastric cancer cells and inhibit the occurrence of autophagy by targeting CAAP1. MKL1 can inhibit the apoptosis of gastric cancer cells and promote the occurrence of autophagy by targeting CAAP1. At the same time, MKL1 can also increase the expression of miR-5100. Conclusions: Our research reveals the mechanism by which the MKL1/miR-5100/CAAP1 loop regulates apoptosis and autophagy levels in gastric cancer cells, and miR-5100 is expected to become a new potential target for gastric cancer treatment. Keywords: MKL1, miR-5100, CAAP1, Autophagy, Apoptosis, Gastric cancer

Abstract Background Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. But the exact molecular mechanism of ERα-36 and STAT3 on metastasis is still not fully understood. Methods MCF-7 and MDA-MB-231 human breast cancer cell lines and MCF-10A were overexpressioned or knockdown ERα-36 and STAT3 and tested for migration, invasion and proliferation assays. Direct interaction of STAT3 and ERα-36 were analyzed by coimmunoprecipitation assays. The effect of STAT3 and ERα-36 on MMP2/9 expression was analyzed by qPCR and western blotting. STAT3 phospholyation and acetylation by ERα-36 and p300 were observed and quantified by coimmunoprecipitation assays and western blotting. Results Cross-talk between ERα-36 and STAT3 was demonstrated to mediate through a direct physical association between the two proteins. Furthermore, the interaction between ERα-36 and STAT3 was demonstrated to give rise to functional changes in their signaling events. Both MMP2 and MMP9 expression require the binding of the newly identified protein complex, ERα-36-STAT3, to its promoter, the second phase, which is more robust, depends on ERα-mediated recruitment of p300 onto the complex and the subsequent acetylation of STAT3. In addition, STAT3 is tyrosine-phosphorylated in a biphasic manner, and the late phase requires ERα-36-mediated p300-dependent acetylation. Furthermore, interference with acetylation of STAT3 by overexpression of acetylation null STAT3 mutant led to the loss of MMP2 and MMP9 expression. ChIP analysis and reporter gene assays revealed that ERα-36-STAT3 complex binding to the MMP2 and MMP9 promoter led to an enhanceosome formation and facilitated MMP2 and MMP9 expression. Conclusions Our studies demonstrate for the first time that the function of MMP2 and MMP9 in breast cancer cell migration, which is mediated by interactions between ERα-36 and STAT3.

The Prandtl-Tomlinson (PT) model is the most widely used and successful minimalistic model to describe atomistic scale friction. It can describe the thermally activated, stress assistant process which shows stick-slip frictional behavior. The relationship between the energy barrier and lateral force is critical to determine how the frictional force depends on velocity and temperature. There is some confusion in the literature to derive such relationship. The underlying assumption and approximations are not stated in a clear way and the rigorous derivations are missing. This study discusses the asymptotic behavior of the energy barrier as the support-spring coupling lowers it to zero and gives a detailed derivation of the asymptotic expression of the energy barrier within the framework of PT model.

The coseismic geothermal changes of ground temperature observed at observatories near the epicenter of the 2020 Jiashi Ms = 6.4 earthquake in China, provide a unique opportunity to study heat generation and conduction in rock. Here, evolutions of rock temperature at the Xikeer, Jiashizongchang, and Gedaliang observatories, which are located at epicentral distances of 1.4, 27.42, and 50 km respectively, were analyzed. Significant coseismic geothermal changes of 0.0432 °C were observed at the Xikeer observatory at the depth of 33.38 m, at which clear diurnal variations can be observed. Smaller changes of ~0.0001 °C were observed at the depths of 12.3 and 22.8 m at the Xikeer observatory and 22.3 m at the Jiashizongchang observatory. The stress transfer induced by the coseismic rupture induced a rise in local ground temperature, but the magnitude of the change was relatively small. The larger amplitude change at the Xikeer observatory was caused by fluid infiltration. We note that diurnal variation has been recorded at the Gedaliang observatory, but the coseismic response is no longer in existence. The temperature increases at the hypocentral area were higher than expected in the ground due to the coseismic stress transfer, but the change attenuated rapidly with distance.

Abstract Vascular endothelial growth factor A (VEGF-A) is a pivotal player in angiogenesis. It is capable of influencing such cellular processes as tubulogenesis and vascular smooth muscle cell (VSMC) proliferation, yet very little is known about the actual signaling events that mediate VEGF-A induced VSMC phenotypic switch. In this report, we describe the identification of an intricate VEGF-A-induced signaling cascade that involves VEGFR2, STAT3, and Myocardin. We demonstrate that VEGF-A promotes VSMC proliferation via VEGFR2/STAT3-mediated upregulating the proliferation of markers like Cyclin D1 and PCNA. Specifically, VEGF-A leads to nitrosylation of Myocardin, weakens its effect on promoting the expression of contractile markers and is unable to inhibit the activation of STAT3. These observations reinforce the importance of nitric oxide and S-nitrosylation in angiogenesis and provide a mechanistic pathway for VEGF-A-induced VSMC phenotypic switch. In addition, Myocardin, GSNOR and GSNO can create a negative feedback loop to regulate the VSMC phenotypic switch. Thus, the discovery of this interactive network of signaling pathways provides novel and unexpected therapeutic targets for angiogenesis-dependent diseases.

Abstract Background Timely identification of deteriorating patients is crucial to prevent the progression to cardiac arrest. However, current methods predicting emergency department cardiac arrest are primarily static, rule-based with limited precision and cannot accommodate time-series data. Deep learning has the potential to continuously update data and provide more precise predictions throughout the emergency department stay. Methods We developed and internally validated a deep learning-based scoring system, the Deep EDICAS for early prediction of cardiac arrest and a subset of arrest, cardiopulmonary resuscitation (CPR), in the emergency department. Our proposed model effectively integrates tabular and time series data to enhance predictive accuracy. To address data imbalance and bolster early prediction capabilities, we implemented data augmentation techniques. Results Our system achieved an AUPRC of 0.5178 and an AUROC of 0.9388 on on data from the National Taiwan University Hospital. For early prediction, our system achieved an AUPRC of 0.2798 and an AUROC of 0.9046, demonstrating superiority over other early warning scores. Moerover, Deep EDICAS offers interpretability through feature importance analysis. Conclusion Our study demonstrates the effectiveness of deep learning in predicting cardiac arrest in emergency department. Despite the higher clinical value associated with detecting patients requiring CPR, there is a scarcity of literature utilizing deep learning in CPR detection tasks. Therefore, this study embarks on an initial exploration into the task of CPR detection.