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The bonding state of the pile-soil interaction is complex. Traditional monitoring methods and tools have not been fully applied to monitor and evaluate it although it affects the lifecycle safety of the pile. In this study, a health monitoring method is proposed to evaluate the bonding state of the pile-soil contact area; it is a transient impact response method based on piezoelectric ceramic sensors to monitor the pile-soil bonding state. During the test, different damage degrees of the pile-soil bonding state were simulated by considering the working conditions of different soil densities and different crack depths as examples. A horizontal transient impact stress was applied to the pile top, and a piezoelectric ceramic sensor embedded in the pile detected the stress wave. As the stress wave response differs in different damage conditions, an energy index was established to quantitatively monitor the degree of damage.

N6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myelogenous leukemia (AML). Identification of the key regulators of m6A modifications in AML could provide further insights into AML biology and uncover more effective therapeutic strategies for patients with AML. Here, we report overexpression of YTHDF1, an m6A reader protein, in human AML samples at the protein level with enrichment in leukemia stem cells (LSC). Whereas YTHDF1 was dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuated self-renewal, proliferation, and leukemic capacity of primary human and mouse AML cells in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of cyclin E2 in an m6A-dependent manner. Structure-based virtual screening of FDA-approved drugs identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocked the direct binding of YTHDF1 with m6A-modified mRNAs and inhibited YTHDF1-regulated cyclin E2 translation. Moreover, tegaserod reduced the viability of patient-derived AML cells in vitro and prolonged survival in patient-derived xenograft models. Together, our study defines YTHDF1 as an integral regulator of AML progression by regulating the expression of m6A-modified mRNAs, which might serve as a potential therapeutic target for AML.Significance:The m6A reader YTHDF1 is required for progression of acute myelogenous leukemia and can be targeted with the FDA-approved drug tegaserod to suppress leukemia growth.

Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive oral tumors. The aim of this study was to establish a nomogram to predict overall survival (OS) of TSCC patients after surgery. 169 TSCC patients who underwent surgical treatments in the Cancer Hospital of Shantou University Medical College were included. A nomogram based on Cox regression analysis results was established and internally validated using bootstrap resampling method. pTNM stage, age and total protein, immunoglobulin G, factor B and red blood cell count were identified as independent prognostic factors to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of pTNM stage, indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected concordance index of nomogram was higher than that of pTNM stage (0.794 vs. 0.665, p = 0.0008). The nomogram also had a good calibration and improved overall net benefit. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (p

Ubiquitin is a small protein that can be added onto target protein for inducing target degradation, thereby modulating the activity and stability of protein. Relatively, deubiquitinases (DUBs), a class catalase that can remove ubiquitin from substrate protein, provide a positive regulation of the protein amount at transcription level, post-translational modification, protein interaction, etc. The reversible and dynamic ubiquitination-deubiquitination process plays an essential role in maintaining protein homeostasis, which is critical to almost all the biological processes. Therefore, the metabolic dysregulation of deubiquitinases often lead to serious consequences, including the growth and metastasis of tumors. Accordingly, deubiquitinases can be served as key drug targets for the treatment of tumors. The small molecule inhibitors targeting deubiquitinases has become one of the hot spots of anti-tumor drug research areas. This review concentrated on the function and mechanism of deubiquitinase system in the proliferation, apoptosis, metastasis and autophagy of tumor cells. The research status of small molecule inhibitors of specific deubiquitinases in tumor treatment is introduced, aiming to provide reference for the development of clinical targeted drugs.

Objective: To develop a clinical prediction model for the risk of distant metastasis in patients with intrahepatic cholangiocarcinoma, to assess the risk of distant metastasis and prognosis of patients, and to explore the efficacy of radiotherapy and chemotherapy in people with different risks of distant metastasis. Method: Clinicopathological data of 15,497 patients diagnosed with intrahepatic cholangiocarcinoma from January 2000 to December 2018were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and all eligible patients were randomly divided into a training cohort and a validation cohort in a 7:3 ratio. Univariate and multivariate logistic regression analyses were performed on the training cohort to identify independent factors for distant metastasis. A prediction model for distant metastasis in patients with intrahepatic ductal carcinoma was constructed based on the independent risk factors for distant metastasis. Receiver Operating Characteristic (ROC) and calibration curves were used to assess the predictive accuracy of the model, and Decision Curve Analysis (DCA) was used to evaluate the clinical utility of the column line graphs.Tumor distant metastasis risk stratification and subgroup survival analysis were performed according to the model, and the benefits of radiotherapy and chemotherapy were explored with the help of the model. Result: Multivariable logistic analysis showed that age, T-stage, N-stage, degree of differentiation, and tumor size were independent risk factors for distant metastasis. The area under the ROC curve (AUC value) was 0.733 (CI95%: 0.713-0.753) and 0.750 (CI95%:0.721-0.780) for the training and validation sets, respectively, and the calibration curves indicated good agreement between predicted and actual values, and the decision curves showed good clinical utility of the model.Subgroup survival analysis suggested that the prognosis is poor in the intermediate and high risk groups, and that radiotherapy and chemotherapy canimprove the prognosis in these groups, with no benefit for the low risk groups. Conclusion: The prediction model of distant metastasis in patients with intrahepatic cholangiocarcinoma based on the SEER database has good prediction accuracy, which helps physicians to assess the risk of distant metastasis and prognosis of patients, thus providing a reference for individualized clinical treatment decisions for patients. Chemotherapy and radiotherapy can significantly improve the survival prognosis of patients with intermediate and high risk of distant metastasis.

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N6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myelogenous leukemia (AML). Identification of the key regulators of m6A modifications in AML could provide further insights into AML biology and uncover more effective therapeutic strategies for patients with AML. Here, we report overexpression of YTHDF1, an m6A reader protein, in human AML samples at the protein level with enrichment in leukemia stem cells (LSC). Whereas YTHDF1 was dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuated self-renewal, proliferation, and leukemic capacity of primary human and mouse AML cells in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of cyclin E2 in an m6A-dependent manner. Structure-based virtual screening of FDA-approved drugs identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocked the direct binding of YTHDF1 with m6A-modified mRNAs and inhibited YTHDF1-regulated cyclin E2 translation. Moreover, tegaserod reduced the viability of patient-derived AML cells in vitro and prolonged survival in patient-derived xenograft models. Together, our study defines YTHDF1 as an integral regulator of AML progression by regulating the expression of m6A-modified mRNAs, which might serve as a potential therapeutic target for AML.Significance:The m6A reader YTHDF1 is required for progression of acute myelogenous leukemia and can be targeted with the FDA-approved drug tegaserod to suppress leukemia growth.

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Supplementary Tables 1-4, Figure Legend from Association of Specific Genotypes in Metastatic Suppressor HTPAP with Tumor Metastasis and Clinical Prognosis in Hepatocellular Carcinoma

The phosphatidic acid phosphatase HTPAP has been defined as a metastatic suppressor of hepatocellular carcinoma (HCC), but little is known about its function or potential applications as a prognostic marker. In this study, we analyzed patterns of HTPAP genetic variation and gene expression in 864 patients who underwent HCC resection, assessing these patterns for correlations to tumor metastasis potential. Focusing on two tagSNPs that were selected (+357G/C and +1838A/G), we found that only the +357G/C genotype was significantly associated with HTPAP mRNA and protein expression levels and the probability of metastasis. In an independent cohort of 665 HCC patients, we determined that the +357G/C genotype was associated with shorter time to recurrence and overall survival. Together, these results indicated that the HTPAP tagSNP +357 GG+GC genotypes may influence HCC metastatic potential and clinical prognosis by down-regulating HTPAP expression. Extending these results, a global expression profiling analysis identified 41 genes including the pro-inflammatory genes IL-8 and TLR2 that were significantly overexpressed in the +357 GG+GC group, as possible coregulated markers with HTPAP. Together, our findings identify an HTPAP genotype and associated gene expression pattern that favors metastasis progression and that could be used to predict tumor metastasis and prognosis in HCC patients. Cancer Res; 71(9); 3278–86. ©2011 AACR.

Supplementary Figure 1 from Association of Specific Genotypes in Metastatic Suppressor HTPAP with Tumor Metastasis and Clinical Prognosis in Hepatocellular Carcinoma

Sulfur vacancies on MoS2 enhanced the activation of peroxymonosulfate to remove organic pollutants in wastewater.

This paper established the equivalent linear motion equation of TRMD. To further investigate the potential application of the TRMD in nonlinear vibration, the Bouc-wen nonlinear model of the structure with TRMD is provided, the vibration control efficacy of TRMD and hysteretic characteristics of the main structure under harmonic excitation are analyzed. The results show that TRMD suppresses the main structure displacement of the Bouc-wen hysteretic nonlinear structure while the hysteretic loop energy dissipation capacity of the structure itself is reduced. For some seismic excitations, the control effect of TRMD on the nonlinear structure is very obvious, but because the spectral characteristics of different seismic excitations generally vary greatly, the control effect of TRMD on the main structure displacement also varies greatly.

Breast cancer (BC) is one of the frequently diagnosed cancers, and the leading cause of cancer-related death among women worldwide. The roles of protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) in human cancer have been exploring, but the clinical significance and biological function of PCMT1 in BC are not yet clear. In this study, based on the TCGA-BRCA data set, the results showed that high expression of PCMT1 gene was significantly correlated with shorter overall survival (OS), disease specific survival (DSS) and progress free suvival (PFS) of BC patients. Utilizing the immunohistochemical assay, we found that PCMT1 protein was located in the cytoplasm of BC cells, and PCMT1 expression was only obviously correlated with progesterone receptor expression of patients (p

Background Esophagogastric junction adenocarcinoma (EJA) lacks serum biomarkers to assist in diagnosis and prognosis. Here, we aimed to evaluate the diagnostic and prognostic value of serum insulin-like growth factor binding protein 3 (IGFBP3) in EJA patients. Methods 320 participants were recruited from November 2016 to January 2020, who were randomly divided into a training cohort (112 normal controls and 102 EJA patients including 24 early-stage patients) and a validation cohort (56 normal controls and 50 EJA patients including 12 early-stage patients). We used receiver operating characteristics curve (ROC) to evaluate diagnostic value. The predictive performance of the nomogram was evaluated by the concordance index (C-index). Results Serum IGFBP3 levels were significantly lower in early-stage EJA or EJA patients than those in controls (P Conclusions We found that serum IGFBP3 was a potential diagnostic and prognostic marker of EJA. Meanwhile, the nomogram might predict the prognosis of EJA more accurately and efficiently.

With the amount of data generated by Internet of Things (IoT) devices increase dramatically, the insufficient computing ability of terminal devices becomes obvious when processing massive computing tasks. The computing tasks need to be offloaded from resource-constrained devices to edge servers with stronger computing capability. It is a challenge for computing offloading to achieve global optimization with multiple objectives such as minimizing task completion times, optimizing energy consumption and maintaining load balancing as the network state and task demands dynamically change. This paper presents optimized edge computing offloading algorithm for software-defined IoT. First, to provide global state for making decisions, a software defined edge computing (SDEC) architecture is proposed. The edge layer is integrated into the control layer of software-defined IoT, and multiple controllers share the global network state information via east-west message exchange. Moreover, an edge computing offloading algorithm in software-defined IoT (ECO-SDIoT) based on deep reinforcement learning is proposed. It enables the controllers to offload the computing task to the most appropriate edge server according to the global states, task requirements, and reward. Finally, the performance metrics for edge computing offloading were evaluated in terms of unit task processing latency, load balancing of edge servers, task processing energy consumption, and task completion rate, respectively. Simulation results show that ECO-SDIoT can effectively reduce task completion time and energy consumption compared with other strategies.

N6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myeloid leukemia (AML), while the detailed mechanism remains elusive. Here we report that YTHDF1, an m6A reader protein, is overexpressed in human AML samples with enrichment in leukemia stem cells (LSCs). Whereas YTHDF1 is dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuates self-renewal and proliferation of patient-derived LSCs, and impedes leukemia establishment in immunodeficient mice. Mechanistically, YTHDF1 promotes the translation of diverse m6A-modified oncogene mRNAs particularly cyclin E2. We applied a structure-based virtual screening of FDA-approved drugs and identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocks the direct binding of YTHDF1 with m6A-modified mRNAs and inhibits YTHDF1-regulated mRNA translation. Moreover, tegaserod inhibits leukemogenesis in vitro and in mice, phenocopying the loss of YTHDF1. Together, our study defines YTHDF1 as an integral regulator of AML progression at the translational level and identifies tegaserod as a potential therapeutic agent for AML by targeting YTHDF1.Statement of SignificanceThe RNA m6A reader YTHDF1 is an oncoprotein in AML.YTHDF1 promotes the translation of m6A-modified oncogene mRNAs.Tegaserod, an FDA-approved drug for irritable bowel syndrome, inhibits YTHDF1-regulated mRNA translation and leukemogenesis.Graphical Abstract

The transcriptional capacities of target genes are strongly influenced by promoters, whereas few studies have focused on the development of robust, high-performance and cross-species promoters for wide application in different bacteria. In this work, four novel promoters (Pk.rtufB, Pk.r1, Pk.r2, and Pk.r3) were predicted from Ketogulonicigenium robustum and their inconsistency in the -10 and -35 region nucleotide sequences indicated they were different promoters. Their activities were evaluated by using green fluorescent protein (gfp) as a reporter in different species of bacteria, including K. vulgare SPU B805, Pseudomonas putida KT2440, Paracoccus denitrificans PD1222, Bacillus licheniformis and Raoultella ornithinolytica, due to their importance in metabolic engineering. Our results showed that the four promoters had different activities, with Pk.r1 showing the strongest activity in almost all of the experimental bacteria. By comparison with the commonly used promoters of E. coli (tufB, lac, lacUV5), K. vulgare (Psdh, Psndh) and P. putida KT2440 (JE111411), the four promoters showed significant differences due to only 12.62% nucleotide similarities, and relatively higher ability in regulating target gene expression. Further validation experiments confirmed their ability in initiating the target minCD cassette because of the shape changes under the promoter regulation. The overexpression of sorbose dehydrogenase and cytochrome c551 by Pk.r1 and Pk.r2 resulted in a 22.75% enhancement of 2-KGA yield, indicating their potential for practical application in metabolic engineering. This study demonstrates an example of applying bioinformatics to find new biological components for gene operation and provides four novel promoters with broad suitability, which enriches the usable range of promoters to realize accurate regulation in different genetic backgrounds.

The primary goal of an exploratory oncology clinical trial is to identify an effective drug for further development. To expedite the drug development process and increase the chance of finding acti...

Background It has been demonstrated that ischemic preconditioning (IPC), and ischemic postconditioning (IPost) have a significant protective effect on myocardial ischemia/reperfusion (MI/R) injury by alleviating oxidative stress and mitochondrial disturbances, although the underlying molecular mechanisms are not clear. To demonstrate that cardioprotection against anoxia/reoxygenation (A/R) injury is transduced via the Notch1/Hes1/VDAC1 signaling pathway. Methods Using proteomics techniques, liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and tandem affinity purification (TAP), to screen for differentially expressed proteins associated with Hes1, followed by standard bioinformatics analysis. The co-immunoprecipitation (Co-IP) assay confirmed an interaction between Hes1 and VDAC1 proteins. H9c2 cells were transfected with Hes1 adenoviral N-terminal TAP vector (AD-NTAP/Hes1) and Hes1-short hairpin RNA adenoviral vector (AD-Hes1-shRNA) to establish A/R injury, ischemic preconditioning (IPC), and ischemic postconditioning (IPost) models, respectively. The expression of Hes1 and VDAC1 proteins were measured by western blotting, while the levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptosis were evaluated by flow cytometry. Results AD-NTAP/Hes1 can activate the exogenous protein expression of Hes1, thus decreasing creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activity and promoting cell viability. The study found that VDAC1 was a potential target protein for Hes1 and the overexpression of Hes1 protein expression downregulated protein expression levels of VDAC1, reduced ROS production, stabilized ΔΨm, and inhibited apoptosis in H9c2 cells. Additionally, downregulation of Hes1 protein expression also upregulated VDAC1 protein expression, increased ROS production, imbalanced ΔΨm, promoted cell apoptosis, and attenuated the cardioprotection afforded by IPC and IPost. Conclusions The Notch1/Hes1 signaling pathway activated by IPC/IPost can directly downregulate the protein expression of VDAC1 and consequently relieve A/R injury.

ObjectivesAt present, esophageal squamous cell carcinoma (ESCC) patients accepting neoadjuvant chemoradiotherapy (nCRT) plus surgery lack corresponding prognostic indicators. This study aimed to construct a prognostic prediction model for ESCC patients undergoing nCRT and surgery based on immune and inflammation-related indicators.MethodsWe retrospectively analyzed the levels of serum immune- and inflammation-related indicators of ESCC patients before receiving nCRT plus surgery in the training cohort (99 patients) and validation cohort (67 patients), which were collected from 2007 to 2020. Univariate and multivariate Cox survival analyses were conducted to evaluate the indicators to set up a nomogram associated with the patients’ overall survival (OS). The prediction accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), decision curve, calibration curve, integrated discrimination improvement (IDI), and net reclassification improvement (NRI).ResultsUnivariate and multivariate Cox analyses demonstrated that immune globin A (IgA) and C-reactive protein (CRP) were independent risk factors. A nomogram based on IgA, CRP, and cTNM stage was established for predicted OS in the training cohort and validated in the validation cohort. The C-index of the nomogram was 0.820 (95% CI: 0.705–0.934), which was higher than that of the cTNM stage (0.655 (95% CI: 0.546–0.764),p< 0.05) in the training cohort, and similar results were observed in the validation cohort (0.832 (95% CI: 0.760–0.903 vs 0.635 (95% CI: 0.509–0.757),p< 0.001). Furthermore, the prediction accuracy and net benefit of the nomogram verified by the calibration curve, decision curve, NRI, and IDI were satisfactory in the training and validation cohorts.ConclusionThe newly constructed nomogram concluding serum IgA, CRP, and cTNM stage might be helpful in the prognosis prediction for ESCC patients receiving nCRT plus surgery.

Purpose: To evaluate the efficacy and safety of different types of anesthesia (LA, LA with IVA, and GA) used during PKP.Patients and methods: A total of 150 patients of single-level OTLF were prospectively included in this study from February 2019 to February 2020. They were randomly divided into three groups of 50 patients each and treated with GA, LA, or LA with IVA. Severity of back pain was measured preoperatively, intraoperatively, and 1 h, 1 day, 1 month, and 1 year postoperatively using VAS scores. The ODI was administered and the AHVB on lateral thoracolumbar radiographs was measured preoperatively and at 1 month and 1 year postoperatively. The MMSE was administered at 1 and 7 days postoperatively to monitor for the development of POCD.Results: 131 patients completed the full postoperative follow-up schedule. The average duration of surgery in the LA group was slightly longer than the other two groups. The intraoperative VAS score of the LA+IVA group was significantly lower than that of the LA group. The MMSE scores at 1 day and 1 week postoperatively were significantly decreased only in the GA group. The incidence of POCD was 45% (18/40) at 1 day and 5% (2/40) and at 1 week postoperatively in the GA group, whereas POCD was not observed in the other two groups. The GA group had the highest incidence of anesthesia-related adverse reactions.Conclusion: IVA with ropivacaine can effectively reduce intraoperative and early postoperative pain, shorten the duration of surgery, reduce surgery-related complications.

Background CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB–IV melanoma. Methods Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety. Results Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3+ infiltrates. Surprisingly, the baseline cell density of CD3+CD8− T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (P = 0.0179). Conclusions These findings suggest responses to this combination may be seen even in patients without a typical “immune-active” microenvironment. Trial registration number NCT02565992.

Pulmonary arterial hypertension (PAH) is a fatal disease whose molecular mechanism is unknown. The trimethylation of lysine 36 on histone 3 (H3K36me3) catalyzed by SETD2 and the modification of N6-methyladenine (m6A) mRNA mediated by METTL14 play important roles in a variety of normal and pathological biological processes. However, the role of these epigenetic controls in the pathogenesis of PAH remains unclear. In this study, the expression of SETD2 and METTL14 was elevated in pulmonary artery smooth muscle cells (PASMCs) of hypoxia-induced PAH mice. We further constructed a mouse model with SETD2 specific knockout in smooth muscle cells (SETD2SM22α Cre). Our results suggest that the lack of SETD2 in SMCs protected mice from hypoxia-induced PAH and significantly reduced right ventricular systolic pressure (RVSP), right ventricular/left ventricular plus septum [RV/(LV+S)] weight ratio, and pulmonary median width. In addition, the absence of SETD2 in SMCs alleviates the level of METTL14 expression and the m6A RNA methylation level in PAH SMCs. These results obtained from mice suggest that strategies that target the inhibition of SETD2/METTL14 activity may be a viable treatment for PAH in a clinical setting.

The development of novel wastewater treatment processes that use heterogeneous catalysts to activate hydrogen peroxide (H2O2) with bicarbonate (HCO3−) has been a subject of great interest in recent years; however, significant challenges remain, despite research into numerous metal-based catalysts. The work presented herein employed oxygen-doped graphitic carbon nitride (O/g-C3N4) as a non-metal catalyst for activating H2O2 in the presence of HCO3−, and this method represented the first system capable of removing organic pollutants in the dark, to our knowledge. The catalysts were characterized using several microscopic imaging, spectroscopic, electrochemical, and crystallographic techniques, as well as N2-physorption procedures. Analysis of the results revealed that the O/g-C3N4 catalyst possessed a high specific surface area and many defect sites. Various operational parameters, including the relative amounts of HCO3−, H2O2, and O/g-C3N4, were systemically investigated. A clear performance enhancement was observed in the degradation of organic contaminants when subjected to the HCO3−–H2O2–O/g-C3N4 system, and this result was ascribed to the synchronous adsorption and chemical oxidation processes. The novel system presented herein represented a new water treatment technology that was effective for removing organic contaminants.

Despite the intensive development of heterogeneous catalysts with transition metal for the Guerbet reaction, a detailed understanding of the metal species and reaction mechanism (rate-determining s...

Myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) is a subtype of MDS/MPN that exhibits a combination of the features of both MDS and MPN. To date, no curative treatment is available for MDS/MPN-U; however, previous studies have suggested a potential survival advantage for ruxolitinib and hypomethylating agents. We reported a case of a JAK2-negative but KRAS-positive MDS/MPN-U patient treated with ruxolitinib plus decitabine. After treatment, the patient's clinical symptoms were moderated, and the size of the spleen and the peripheral blood cell counts were reduced. These effects might be due to the regimen's ability to reduce STAT5 activation and upregulate microRNA-181c to downregulate the variant allele frequency (VAF) of KRAS.

Small-particle interlayers (lenticles) show some characteristic hydraulic properties and can affect the movement of unsaturated water. In this study, we developed a novel online capillary-water-absorption monitoring device and conducted three groups of comparison tests to simulate lenticle positions and thicknesses with respect to the capillary rise. The results show that the characteristic wetting front exhibits a fast rise in the early stage, a slow rise in the middle stage, and stability in the later stage. The motion of the capillary water in the lenticle is mainly transversal, with the upward curve being “flat,” and the longer is “flat,” the longer is the time needed for the water to move. The interlayer can form a capillary stagnation zone with moisture content close to saturation. The high interlayer may form a discontinuous corrugated capillary zone. Thus, when the wetting front reaches the “coarse-grain (lower)-fine-grain (upper)” interface, the “anti-capillary barrier effect” results in more moisture in the upper layer. Thus, when the wetting front of the capillary water reaches the “fine-grain (upper)-coarse-grain (lower)” interface, the “capillary barrier effect” causes the moisture content of the upper tailings to decreases sharply because of the horizontal movement of the water in the fine medium. It is clear that the presence of lenticles can retard the rise of capillary water by storing water.

The paper introduces the research background, current status and performance of architectural membrane materials, analyzes the superiority of PVC and PTFE performance, discusses the aging and standards of architectural membrane materials, and conducts new rheological destruction of architectural membrane materials. The aging and relaxation characteristics described by the constitutive equations, and the viscos-elastoplastic rheological failure of architectural membranes for constitutive experiments. At the end of the thesis, the aging performance degradation of architectural membrane materials is discussed, and the aging of architectural membrane materials and the significance of membrane performance degradation are explored in depth.