Detection of Endoleak after Endovascular Aortic Repair through Deep Learning Based on Non-contrast CT.

OBJECTIVES: To develop and validate a deep learning model for detecting post-endovascular aortic repair (EVAR) endoleak from non-contrast CT. METHODS: This retrospective study involved 245 patients who underwent EVAR between September 2016 and December 2022. All patients underwent both non-enhanced and enhanced follow-up CT. The presence of endoleak was evaluated based on computed tomography angiography (CTA) and radiology reports. First, the aneurysm sac was segmented, and radiomic features were extracted on non-contrast CT. Statistical analysis was conducted to investigate differences in shape and density characteristics between aneurysm sacs with and without endoleak. Subsequently, a deep learning model was trained to generate predicted segmentation of the endoleak. A binary decision was made based on whether the model produced a segmentation to detect the presence of endoleak. The absence of a predicted segmentation indicated no endoleak, while the presence of a predicted segmentation indicated endoleak. Finally, the performance of the model was evaluated by comparing the predicted segmentation with the reference segmentation obtained from CTA. Model performance was assessed using metrics such as dice similarity coefficient, sensitivity, specificity, and the area under the curve (AUC). RESULTS: This study finally included 85 patients with endoleak and 82 patients without endoleak. Compared to patients without endoleak, patients with endoleak had higher CT values and greater dispersion. The AUC in validation group was 0.951, dice similarity coefficient was 0.814, sensitivity was 0.877, and specificity was 0.884. CONCLUSION: This deep learning model based on non-contrast CT can detect endoleak after EVAR with high sensitivity.

Transcriptomic analysis reveals the critical role of chemokine signaling in the anti-atherosclerosis effect of Xuefu Zhuyu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: The process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. AIM: This study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. MATERIALS AND METHODS: AS models were established by subjecting ApoE-/-mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaque was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. RESULTS: After ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the Cytokine-cytokine receptor interaction pathway and Chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12, Ccl22, Cx3cr1, Ccr7, Ccr2, Tnfrsf25, and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, in cell models, the mRNA expressions of Ccl12, Ccl22, and Ccr2 were significantly upregulated (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12, Ccl22, Cx3cr1, Ccr7 and Ccr2 (P < 0.05 or P < 0.01). CONCLUSION: Xuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the Cytokine-cytokine receptor interaction and Chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies.

Discharge coefficient of vertical sluice gates with broad crested weir under free-submerged orifice flows using best subset regression.

Accurate calculation of flow discharge for sluice gates is essential in irrigation, water supply, and structure safety. The measurement of discharge with the requirement of distinguishing flow regimes is not conducive to application. In this study, a novel approach that considers both free and submerged flow was proposed. The energy-momentum method was employed to derive the coefficient of discharge. Subsequently, the discharge coefficient was determined through the experiment which was performed on the physical model of a vertical sluice gate with a broad-crested weir. Feature engineering, incorporating dimensional analysis, feature construction, and correlation-based selection were performed. The best subset regression method was employed to develop regression equations of the discharge coefficient with the generated features. The derived formula was applied to compute the discharge coefficient in the vertical sluice gate and determine the flow discharge. The accuracy of adopted method was assessed by comparing it with recent studies on submerged flow, and the results demonstrate that the developed approach achieves a high level of accuracy in calculating flow discharge. The coefficient of determination for the calculated flow rate is 0.993, and the root mean square percentage error is 5.04%.

Pathological features and molecular signatures of early olfactory dysfunction in 3xTg-AD model mice.

BACKGROUND: Olfactory dysfunction is known to be an early manifestation of Alzheimer's disease (AD). However, the underlying mechanism, particularly the specific molecular events that occur during the early stages of olfactory disorders, remains unclear. METHODS: In this study, we utilized transcriptomic sequencing, bioinformatics analysis, and biochemical detection to investigate the specific pathological and molecular characteristics of the olfactory bulb (OB) in 4-month-old male triple transgenic 3xTg-AD mice (PS1M146V/APPSwe/TauP301L). RESULTS: Initially, during the early stages of olfactory impairment, no significant learning and memory deficits were observed. Correspondingly, we observed significant accumulation of amyloid-beta (Aß) and Tau pathology specifically in the OB, but not in the hippocampus. In addition, significant axonal morphological defects were detected in the olfactory bulb, cortex, and hippocampal brain regions of 3xTg-AD mice. Transcriptomic analysis revealed a significant increase in the expression of neuroinflammation-related genes, accompanied by a significant decrease in neuronal activity-related genes in the OB. Moreover, immunofluorescence and immunoblotting demonstrated an activation of glial cell biomarkers Iba1 and GFAP, along with a reduction in the expression levels of neuronal activity-related molecules Nr4a2 and FosB, as well as olfaction-related marker OMP. CONCLUSION: In sum, the early accumulation of Aß and Tau pathology induces neuroinflammation, which subsequently leads to a decrease in neuronal activity within the OB, causing axonal transport deficits that contribute to olfactory disorders. Nr4a2 and FosB appear to be promising targets for intervention aimed at improving early olfactory impairment in AD.

Revealing PPP1R12B and COL1A1 as piRNA pathway genes contributing to abdominal aortic aneurysm through integrated analysis and experimental validation.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a permanent dilation of the abdominal aorta, with a high mortality rate when rupturing. Although lots of piRNA pathway genes (piRPGs) have recently been linked to both neoplastic and non-neoplastic illnesses, their role in AAA is still unknown. Utilizing integrative bioinformatics methods, this research discovered piRPGs as biomarkers for AAA and explore possible molecular mechanisms. METHODS: The datasets were obtained from the Gene Expression Omnibus and piRPGs were identified from the Genecards database. The "limma" and "clusterProfiler" R-packages were used to discover differentially expressed genes and perform enrichment analysis, respectively. Hub piRPGs were further filtered using least absolute shrinkage and selection operator regression, random forests, as well as receiver operating characteristic curve. Additionally, multi-factor logistic regression (MLR), extreme gradient boosting (XGboost), and artificial neural network (ANN) were employed to construct prediction models. The relationship between hub piRPGs and immune infiltrating cells and sgGSEA were further studied. The expression of hub piRPGs was verified by qRT-PCR, immunohistochemistry, and western blotting in AAA and normal vascular tissues and analyzed by scRNA-seq in mouse AAA model. SRAMP and cMAP database were utilized for the prediction of N6-methyladenosine (m6A) targets therapeutic drug. RESULTS: 34 differentially expressed piRPGs were identified in AAA and enriched in pathways of immune regulation and gene silence. Three piRPGs (PPP1R12B, LRP10, and COL1A1) were further screened as diagnostic genes and used to construct prediction model. Compared with MLR and ANN, Xgboost showed better predictive ability, and PPP1R12B might have the ability to distinguish small and large AAA. Furthermore, the expression levels of PPP1R12B and COL1A1 were consistent with the results of bioinformatics analysis, and PPP1R12B showed a downward trend that may be related to m6A. CONCLUSION: The results suggest that piRPGs might serve a significant role in AAA. PPP1R12B, COL1A1, and LRP10 had potential as diagnostic-specific biomarkers for AAA and performed better in XGboost model. The expression and localization of PPP1R12B and COL1A1 were experimentally verified. Besides, downregulation of PPP1R12B caused by m6A might contribute to the formation of AAA.

Stability analysis of riverbanks with a dual structure under water-root-soil coupling.

The collapse mechanism of dual-structure vegetation riverbanks at different water levels is unclear. A method for calculating the critical collapse width of a dual-structure vegetation bank under different failure modes that consider the variations in river and groundwater levels and the influence of vegetation roots is proposed. Combined with the influence of flow lateral erosion and slope toe accumulation, a calculation model of riverbank stability was established. The results show that shear failure is the main failure mode when the cohesive soil layer on a dual-structure bank is thick, and the critical collapse width of the bank with root soil is higher than that of the soil bank. The critical collapse width of the bank varied with the water level during different water level periods. Compared with a soil riverbank, a rooted soil riverbank can significantly prolong the bank collapse time. The collapse width of a soil bank without vegetation roots is smaller than that of a rooted soil bank, and the cumulative collapse width is related to calculation time. The greater the thickness of rooted soil, the slower the decay rate of bank stability under water flow erosion.

Integrative analysis of DNA methylome and transcriptome reveals epigenetic regulation of bisphenols-induced cardiomyocyte hypertrophy.

Cardiac hypertrophy, a kind of cardiomyopathic abnormality, might trigger heart contractile and diastolic dysfunction, and even heart failure. Currently, bisphenols (BPs) including bisphenol A (BPA), and its alternatives bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) are ubiquitously applied in various products and potentially possess high cardiovascular risks for humans. However, the substantial experimental evidences of BPs on heart function, and their structure-related effects on cardiomyocyte hypertrophy are still urgently needed. DNA methylation, a typical epigenetics, play key roles in BPs-induced transcription dysregulation, thereby affecting human health including cardiovascular system. Thus, in this study, we performed RNA-seq and reduced representation bisulfite sequencing (RRBS) to profile the landscapes of BPs-induced cardiotoxicity and to determine the key roles of DNA methylation in the transcription. Further, the capabilities of three BPA analogues, together with BPA, in impacting heart function and changing DNA methylation and transcription were compared. We concluded that similar to BPA, BPAF, BPF and BPS exposure deteriorated heart function in a mouse model, and induced cardiomyocyte hypertrophy in a H9c2 cell line. BPAF, BPF and BPS all played BPA-like roles in both transcriptive and methylated hierarchies. Moreover, we validated the expression levels of four cardiomyocyte hypertrophy related candidate genes, Psmc1, Piptnm2, Maz and Dusp18, which were all upregulated and with DNA hypomethylation. The findings on the induction of BPA analogues on cardiomyocyte hypertrophy and DNA methylation revealed their potential detrimental risks in heart function of humans.

Systemic alterations of tricarboxylic acid cycle enzymes in Alzheimer's disease.

Mitochondrial dysfunction, especially tricarboxylic acid (TCA) cycle arrest, is strongly associated with Alzheimer's disease (AD), however, its systemic alterations in the central and peripheral of AD patients are not well defined. Here, we performed an integrated analysis of AD brain and peripheral blood cells transcriptomics to reveal the expression levels of nine TCA cycle enzymes involving 35 genes. The results showed that TCA cycle related genes were consistently down-regulated in the AD brain, whereas 11 genes were increased and 16 genes were decreased in the peripheral system. Pearson analysis of the TCA cycle genes with Aß, Tau and mini-mental state examination (MMSE) revealed several significant correlated genes, including pyruvate dehydrogenase complex subunit (PDHB), isocitrate dehydrogenase subunits (IDH3B, IDH3G), 2-oxoglutarate dehydrogenase complex subunit (DLD), succinyl-CoA synthetase subunit (SUCLA2), malate dehydrogenase subunit (MDH1). In addition, SUCLA2, MDH1, and PDHB were also uniformly down-regulated in peripheral blood cells, suggesting that they may be candidate biomarkers for the early diagnosis of AD. Taken together, TCA cycle enzymes were systemically altered in AD progression, PDHB, SUCLA2, and MDH1 may be potential diagnostic and therapeutic targets.

Integrated transcriptomics reveals the brain and blood biomarkers in Alzheimer's disease.

BACKGROUND: The systematic molecular associations between the peripheral blood cells and brain in Alzheimer's disease (AD) remains unclear, which hinders our understanding of AD pathological mechanisms and the exploration of new diagnostic biomarkers. METHODS: Here, we performed an integrated analysis of the brain and peripheral blood cells transcriptomics to establish peripheral biomarkers of AD. By employing multiple statistical analyses plus machine learning, we identified and validated multiple regulated central and peripheral network in patients with AD. RESULTS: By bioinformatics analysis, a total of 243 genes were differentially expressed in the central and peripheral systems, mainly enriched in three modules: immune response, glucose metabolism and lysosome. In addition, lysosome related gene ATP6V1E1 and immune response related genes (IL2RG, OSM, EVI2B TNFRSF1A, CXCR4, STAT5A) were significantly correlated with Aß or Tau pathology. Finally, receiver operating characteristic (ROC) analysis revealed that ATP6V1E1 showed high-diagnostic potential for AD. CONCLUSION: Taken together, our data identified the main pathological pathways in AD progression, particularly the systemic dysregulation of the immune response, and provided peripheral biomarkers for AD diagnosis.

Danggui Buxue decoction ameliorates mitochondrial biogenesis and cognitive deficits through upregulating histone H4 lysine 12 acetylation in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement 'blood' and 'qi' (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. AIM OF THE STUDY: This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). MATERIALS AND METHODS: The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot, immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. RESULTS: In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aß accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1. Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. CONCLUSIONS: These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.

Efficacy of salvage therapies after failure of adjuvant anti-PD-1 monotherapy for melanoma in the Chinese population: a multi-institutional cohort study.

The majority of melanoma patients experience relapse during adjuvant therapy or after the end of therapy. Sixty-one patients from 3 melanoma centres who experienced recurrence and received adjuvant pembrolizumab for resected stage III/IV melanoma were enrolled. Disease characteristics, recurrence characteristics, subsequent management and outcomes were retrospectively analysed. Sixty-one patients were enrolled in this study. The median time to first relapse from the commencement of adjuvant pembrolizumab was 8 months (1-22 months). The first recurrences were locoregional alone in 25 patients (41%), distant alone in 29 (47.5%) and concurrent locoregional and distant relapse in 7 (11.5%). At the first recurrence, 4 patients (80%) who underwent resection alone experienced further relapse of disease. Three (60%) patients who were treated with adjuvant pembrolizumab following surgery, 2 (100%) patients who were treated with adjuvant chemotherapy, 2 (66.7%) patients who were treated with adjuvant chemotherapy and pembrolizumab combined and 3 (100%) patients who were treated with adjuvant radiotherapy and pembrolizumab combined had further recurrence. Of the three patients treated with adjuvant BRAF/MEKi following the first relapse, none had yet recurred. Of the 8 patients treated with pembrolizumab alone, only one patient (12.5%) who recurred after ceasing adjuvant PD1 had a partial response. The overall response rate to BRAF/MEKi was 75%, 3/4; to pembrolizumab in combination with an oral multitargeted receptor tyrosine kinase inhibitor, it was 22.2%, 2/9; to chemotherapeutic agents alone, it was 33.3%, 1/3; and to chemotherapeutic agents combined with pembrolizumab, it was 37.5%, 3/8. The patient treated with imatinib had progressive disease after 3 months of treatment. Of the 6 patients who received temozolomide combined with pembrolizumab, 3 (3/6, 50%) had a partial response. The median OS of the patients who relapsed locoregionally only was longer than that of the patients who relapsed distally at the first recurrence (35 months and 14 months, respectively; P < 0.01). The outcomes of the patients with disease recurrence during or after the completion of 1 year of adjuvant anti-PD1 therapy were poor despite multimodality treatment.

Bioinformatics prediction and experimental verification of a novel microRNA for myocardial fibrosis after myocardial infarction in rats.

Background: MicroRNAs (miRNAs) are endogenous noncoding single-stranded small RNAs. Numerous studies have shown that miRNAs have pivotal roles in the occurrence and development of myocardial fibrosis (MF). However, miRNA expression profile in rats with MF after myocardial infarction (MI) is not well understood. The present study aimed to find the potential miRNA for MF post MI. Methods: SPF male Sprague-Dawley (SD) rat models of acute myocardial infarction (AMI) were established by ligating the anterior descending branch of the left coronary artery, while sham-operated rats were only threaded without ligation as a control group. Hematoxylin-eosin and Masson trichrome staining were used to detect myocardial histopathological changes for model evaluation. The differentially expressed miRNAs were detected by using the Agilent Rat miRNA gene chip in the myocardial tissue of the infarct marginal zone. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by DAVID. The expression of miR-199a-5p was verified by real-time fluorescence quantitative PCR (qRT-PCR). Transfected miR-199a-5p mimics into cardiac fibroblasts (CFs) to construct cell models of miR-199a-5p overexpression. Dual-luciferase reporter assay was employed to validate the target gene of miR-199a-5p. The protein expression of the target gene in CFs transfected with miR-199a-5p mimics were detected by Western blot. Results: Myocardial fibrosis was exacerbated in the model group compared with the control group. Thirteen differentially expressed miRNAs between the two groups were screened and their expression levels in the model group were all higher than those in the control group. The expression of miR-199a-5p was significantly increased in the model group in qRT-PCR, which was consistent with the results of the gene chip. KEGG enrichment analysis showed that the target genes of miR-199a-5p were enriched in the insulin signaling pathway. Furthermore, dual-luciferase reporter assay indicated that miR-199a-5p could negatively regulate the expression of GSK-3ß. After transfection, the expression of miR-199a-5p was increased in the miR-199a-5p mimics group. The protein expression of GSK-3ß was decreased in CFs transfected with miR-199a-5p mimics. Conclusion: Our study identified miR-199a-5p could promote the progression of myocardial fibrosis after myocardial infarction by targeting GSK-3ß, which provides novel targets for diagnosis and treatment of MF.

Case report: complete remission with crizotinib in ROS1 fusion-positive sinonasal mucosal melanoma.

Introduction: Sinonasal mucosal melanoma (SNMM) originates from melanocytes. Currently, the main treatment methods, including surgery, radiotherapy and chemotherapy, have little effect on the recurrence and metastasis of SNMM. However, targeted therapy may be a breakthrough in treating SNMM. Methods: A SNMM patient with ROS1 fusion received 250mg Crizotinib capsule (2 times a day, 1 tablet each time) therapy. Results: The patient achieved partial remission after 4 months of treatment and complete remission after 8 months of treatment. Conclusion: Our findings suggest that crizotinib can be an option to improve overall survival and quality of life of patients with metastatic ROS1-fusion SNMM. We believe that our report will provide insights for the application of crizotini in the treatment of melanoma.

Efficacy and Underlying Mechanism of Berberine Against Atherosclerosis: A Meta-Analysis in Preclinical Animal Studies.

ABSTRACT: Atherosclerosis is the primary cause of many cardiovascular diseases, and an increasing number of studies have shown that berberine could delay plaque formation and development. Therefore, we aimed to evaluate its effects and explore its mechanisms in this meta-analysis. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases for original preclinical studies to conduct meta-analysis. Twelve articles (16 studies; 312 ApoE -/- mice) were included, and all the studies scored 3-5 points according to SYRCLE's risk of bias tool. Berberine could significantly decrease plaque area and plaque macrophage content (plaque area, SMD = -2.02, 95% CI: -2.80 to -1.24, P = 0.000; plaque macrophage content, SMD = -4.28, 95% CI: -7.67 to -0.88, P = 0.013); lower the levels of TC, triglyceride, and low-density lipoprotein (TC, SMD = -1.47, 95% CI: -2.20 to -0.74, P = 0.000; triglyceride, SMD = -0.77, 95% CI: -1.21 to -0.33, P = 0.000; low-density lipoprotein, SMD = -0.61, 95% CI: -1.11 to -0.11, P = 0.000), and change the secretion of inflammatory cytokines (IL-1ß, SMD = -2.29, 95% CI: -3.40 to -1.18, P = 0.000; interleukin-6, SMD = -1.48, 95% CI: -2.11 to -0.85, P = 0.008; tumor necrosis factor-α, SMD = -1.98, 95% CI: -3.01 to -0.94, P = 0.000; interleukin-10, SMD = 1.78, 95% CI: 0.76 to 2.80, P = 0.015), but there were no significant differences in high-density lipoprotein levels and plaque lipid content (high-density lipoprotein, SMD = 0.02, 95% CI: -0.35 to 0.40, P = 0.021; plaque lipid content, SMD = -6.85, 95% CI: -21.09 to 7.39, P = 0.007). The results were robust across a range of sensitivity analyses. Therefore, the results indicate that berberine is a promising drug for the treatment of atherosclerosis through regulating lipid metabolism, inflammation, and plaque composition. However, some potential mechanisms remain to be further elucidated.

Super-resolution reconstruction based on BM3D and compressed sensing.

In the various papers published in the field of super-resolution microscopy, denoising of raw images based on block-matching and 3D filtering (BM3D) was rarely reported. BM3D for blocks of different sizes was studied. The denoising ability is related to block sizes. The larger the block is, the better the denoising effect is. When the block size is >40, a good denoising effect can be achieved. Denoising has a great influence on the super-resolution reconstruction effect and the reconstruction time. Better super-resolution reconstruction and shorter reconstruction time can be achieved after denoising. Using compressed sensing, only 20 raw images are needed for super-resolution reconstruction. The temporal resolution is less than half a second. The spatial resolution is also greatly improved.

Impact of the Grain for Green Project on water resources and ecological water stress in the Yanhe River Basin.

The Grain for Green project (GGP), initialized by the Chinese government in 1999, has achieved substantial achievements accompanied by a decrease in surface runoff on the Loess Plateau, but the impacts of large-scale afforestation on regional water resources are uncertain. Hence, the objective of this study was to explore the impact of land use change on generalized water resources and ecological water stress using the blue and green water concepts, taking the Yanhe River Basin as the case study. The Soil and Water Assessment Tool (SWAT) was applied to quantify the green water and blue water, which are defined as generalized water resources. The ecological water requirement of vegetation (forest and grass), agricultural water footprint and virtual water flow are considered regional water requirements. The land use types of 1980 (Scenario I) and 2017 (Scenario II) were entered into the SWAT model while keeping the other parameters constant to isolate the influence of land use changes. The results show that the average annual differences in blue, green and generalized water resources were -72.08 million m3, 24.34 million m3, and -47.74 million m3, respectively, when the simulation results of Scenario II were subtracted from those of Scenario I, which shows that land use change caused by the GGP led to a decrease in blue and generalized water resources and an increase in green water resources. Surface runoff in Scenario I was more than that in Scenario II in all of the years of the study period from 1980-2017, and green water storage in Scenario I was more than that in Scenario II in all of the years of the study period except in 1998; although lateral flow in Scenario I was less than that in Scenario II except in 2000 and 2015, as was groundwater runoff in 1992, 2000 and 2015, and green water flow in 1998. Blue water flow, green water storage and green water flow in Scenario II were less than those in Scenario I in the whole basin, 12.89 percent of the basin and 99.21 percent of the basin, respectively. The total water footprint increased from 1995 to 2010 because the forest water footprint increased significantly in this period, although the agricultural water footprint and grass water footprint decreased. The ecological water stress index values had no obvious temporal change trends in either land use scenario, but the ecological water stress index in Scenario II was greater than that in Scenario I, which illustrates that the GGP led to an increase in ecological water stress from the perspective of generalized water resources.

The regulatory function of piRNA/PIWI complex in cancer and other human diseases: The role of DNA methylation.

Piwi-interacting RNAs (piRNAs) are a class of short chain noncoding RNAs that are constituted by 26-30 nucleotides (nt) and can couple with PIWI protein family. piRNAs were initially described in germline cells and are believed to be critical regulators of the maintenance of reproductive line. Increasing evidence has extended our perspectives on the biological significance of piRNAs and indicated that they could still affect somatic gene expression through DNA methylation, chromatin modification and transposon silencing, etc. Many studies have revealed that the dysregulation of piRNAs might contribute to diverse diseases through epigenetic changes represented by DNA methylation and chromatin modification. In this review, we summarized piRNA/PIWI protein-mediated DNA methylation regulation mechanisms and methylation changes caused by piRNA/PIWI proteins in different diseases, especially cancers. Since DNA methylation and inhibitory chromatin marks represented by histone H3 lysine 9 (H3K9) methylation frequently cooperate to silence genomic regions, we also included methylation in chromatin modification within this discussion. Furthermore, we discussed the potential clinical applications of piRNAs as a new type promising biomarkers for cancer diagnosis, as well as the significance of piRNA/PIWI protein-associated methylation changes in treatment, providing disparate insights into the potential applications of them.

Retrospective Review of Efficacy and Safety of Anlotinib in Advanced Leiomyosarcoma: A Real-World Study.

Objective: Retrospective study on the safety and efficacy of anlotinib in the treatment of advanced leiomyosarcoma in real-world. Methods: Clinical data were collected from patients suffered from advanced leiomyosarcoma who received anlotinib treatment in Cancer Hospital of the University of Chinese Academy of Sciences from January 2018 to December 2020. Objective response rate (ORR) and disease control rate (DCR) were analyzed according to the RECIST 1.1 criteria. The progression free survival (PFS), overall survival (OS) and adverse reactions were recorded and calculated. Results: A total of 19 patients (14 female, 5 male) were enrolled, 3 (15.8%) achieved partial response (PR), 11 (57.9%) achieved stable disease (SD), with an ORR of 15.8%, a DCR of 73.7%, a median PFS of 4.1 months (95% CI: 3.0~5.2) and a median OS of 23.5 months (95% CI: 14.2~32.7). The majority of adverse events were grade 1/2, the most common grade 3/4 adverse events were hand-foot syndrome (12.5%), hypertension (5.3%) and oral ulcer (5.3%). Conclusion: Our results forecast that anlotinib is effective, safe and alternative in treatment of advanced leiomyosarcoma in real-world, combined with immunotherapy may become a potential treatment option. Further, more prospective randomized controlled trials are needed to confirm these findings.

Next Generation Sequencing Reveals Pathogenic and Actionable Genetic Alterations of Soft Tissue Sarcoma in Chinese Patients: A Single Center Experience.

Background: Next generation sequencing (NGS) has systematically investigated the genomic landscape of soft tissue sarcoma (STS) in Western patients, but few reports have described the utility of NGS in identifying pathogenic and targetable mutations in Asian patients. Methods: We review our single center experience of identifying the genomic profile and feasible genetic mutations in 65 Chinese patients with STS by NGS. Results: On average, 3.35 mutations were identified per patient (range, 0-28), and at least one mutation could be detected in 95.4% (62/65) of patients. TP53, MDM2, CDK4, KDR, and NF1 were the most frequent mutation genes in Chinese STS patients. Actionable mutations were discovered in 36.9% (24/65) of patients, and clinical benefit was achieved in 4 patients treated with corresponding molecular targeted therapies. Conclusions: Our study describes the mutation profile of Chinese STS patients by a single center experience. Some patients have achieved improved clinical outcomes by adopting treatment based on the results of genetic testing. NGS may affect clinical decision-making as a routine clinical test for patients with STS.

METTL3-induced UCK2 m6A hypermethylation promotes melanoma cancer cell metastasis via the WNT/ß-catenin pathway.

BACKGROUND: Melanoma is a highly aggressive, malignant skin tumor with a statistically high mortality rate. N6-methyladenosine (m6A) modification is involved in a variety of biological processes, including tumorigenesis. m6A modifications regulate the fate and functions of RNA, such as mRNA stability, nuclear processing, transport, localization, translation, primary microRNA (miRNA) processing, and RNA-protein interactions. Several members (including METTL3, METTL14, FTO, ALKBH5, and YTHDF2) are actively involved in a variety of human cancers. However, the basic mechanism of the involvement of uridine cytidine kinase 2 (UCK2) in melanoma metastasis has not been studied. UCK2 is upregulated in a variety of malignancies. However, the complex molecular mechanisms and therapeutic effects of UCK2 in melanoma remain unclear. METHODS: The expression of UCK2 was evaluated by qRT-PCR. The effects of UCK2 on the biological characteristics of PC cells were investigated on the basis of loss-of-function analyses. Immunoprecipitation-qPCR (MeRIP-qPCR) was performed to identify the m6A targeted effect of UCK2 in melanoma cancer. RESULTS: Based on the bioinformatics analysis in this study, up-regulation of UCK2 could be essential in melanoma cancer, and associated with poor survival. Furthermore, the m6A modification regulated by METTL3 led to UCK2 increased messenger RNA (mRNA) stability in melanoma cancer. Functional and mechanistic experiments indicated that UCK2 enhanced the metastasis of melanoma cancer cells through the WNT/ß-catenin pathway. CONCLUSION: In this study, we found that m6A-METTL3 axis induced abnormal UCK2 expression plays a role in melanoma metastasis by enhancing the Wnt/ß-catenin pathway, which may provide new clues for melanoma metastasis. It also provides a potential target for the prevention and treatment of melanoma.