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Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH + subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo . Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.

Background/objectives: Epidemiological evidence is suggestive, but inconclusive, for an association between consumption of red and processed meat and risk of stroke. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. Subjects/methods: We performed a literature search on PubMed database through June 2012 to indentify prospective cohort studies of red and processed meat intake in relation to risk of stroke. Reference lists of the retrieved articles were also reviewed. Both fixed-effects and random-effects model were assumed to compute the summary risk estimates. Results: Five large independent prospective cohort studies were identified. These studies contained a total of 2 39 251 subjects and 9593 stroke events. Comparing the highest category of consumption with lowest category, the pooled relative risks (RRs) of total stroke were 1.15 (95% confidence interval (CI), 1.05–1.25) for total meat (red and processed meat combined) ( n =4), 1.09 (95% CI, 1.01–1.18) for red meat ( n =5) and 1.14 (95% CI, 1.05–1.25) for processed meat ( n =5); the corresponding RRs of ischemic stroke (highest vs lowest quintile) were 1.15 (95% CI, 1.04–1.28), 1.13(95% CI, 1.01–1.25) and 1.19 (95% CI, 1.08–1.31). Consumption of red and/or processed meat was not associated with hemorrhagic stroke. In the dose–response analysis, the risk of stroke increased significantly by 10% and 13% for each 100 g per day increment in total and red meat consumption, respectively, and by 11% for each 50 g per day increment in processed meat consumption. Conclusion: Findings from this meta-analysis indicate that consumption of red and/or processed meat increase risk of stroke, in particular, ischemic stroke.

Gliomas are highly malignant brain tumors that are highly invasive and resistant to conventional therapy. Receptor tyrosine kinases (RTKs) such as PDGFRα (platelet-derived growth factor receptor-α), which show frequent aberrant activation in gliomas, are associated with a process of epithelial–mesenchymal transition (EMT), a cellular alteration that confers a more invasive and drug-resistant phenotype. Although this phenomenon is well documented in human cancers, the processes by which RTKs including PDGFRα mediate EMT are largely unknown. Here, we report that SHP-2 (encoded by PTPN11 ) upregulates an EMT inducer, ZEB1, to mediate PDGFRα-driven glioma EMT, invasion and growth in glioma cell lines and patient-derived glioma stem cells (GSCs) using cell culture and orthotopic xenograft models. ZEB1 and activated PDGFRα were coexpressed in invasive regions of mouse glioma xenografts and clinical glioma specimens. Glioma patients with high levels of both phospho-PDGFRα (p-PDGFRα) and ZEB1 had significantly shorter overall survival compared with those with low expression of p-PDGFRα and ZEB1. Knockdown of ZEB1 inhibited PDGFA/PDGFRα-stimulated glioma EMT, tumor growth and invasion in glioma cell lines and patient-derived GSCs. PDGFRα mutant deficient of SHP2 binding (PDGFRα-F720) or phosphoinositide 3-kinase (PI3K) binding (PDGFRα-F731/42), knockdown of SHP2 or treatments of pharmacological inhibitor for PDGFRα-signaling effectors attenuated PDGFA/PDGFRα-stimulated ZEB1 expression, cell migration and GSC proliferation. Importantly, SHP-2 acts together with PI3K/AKT to regulate a ZEB1-miR-200 feedback loop in PDGFRα-driven gliomas. Taken together, our findings uncover a new pathway in which ZEB1 functions as a key regulator for PDGFRα-driven glioma EMT, invasiveness and growth, suggesting that ZEB1 is a promising therapeutic target for treating gliomas with high PDGFRα activation.

Recovery of new-energy critical metals including scandium, nickel and cobalt as well as copper and zinc from a neutralization residue produced in laterite hydrometallurgical process has been studied. Effect of leaching parameters such as acid consumption, solution pH and temperature has been investigated. It was found that scandium, nickel, cobalt and copper could be recovered at high efficiencies from the residues by selective leaching using sulphuric acid solutions under ambient conditions, while the co-leaching of impurities including iron, aluminium and silicon was low under the optimal conditions. The nickel, cobalt, copper and zinc in the leaching solution could be further concentrated into mixed sulphides and separated from impurities by sulphide precipitation.

Background/Objectives: Epidemiological studies have suggested that dietary fiber intake may be associated with a decreased risk of stroke, but the findings have been inconsistent. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. Subjects/Methods: We performed a literature search on PubMed database through July 2012 to indentify prospective studies of dietary fiber intake in relation to risk of stroke. We also comprehensively reviewed the reference lists of the retrieved articles to identify additional studies. We used a random-effects model to compute the summary risk estimates. Results: Six prospective cohort studies containing a total of 314 864 subjects and 8920 stroke cases were included. The summary relative risk (RR) of stroke for the highest vs lowest category of dietary fiber intake was 0.87 (95% confidence interval (CI), 0.77–0.99). The corresponding RR in the subgroup analyses for men and women was 0.95 (95% CI, 0.83–1.08) and 0.80 (95% CI, 0.66–0.96), respectively; and for ischemic stroke and hemorrhagic stroke was 0.83(95% CI, 0.72–0.96) and 0.86 (95% CI, 0.70–1.06), respectively. Meta-regression indicated no significant difference between gender ( P -interaction=0.18), or stroke subtypes ( P -interaction =0.85). The dose-response analysis suggested a 12% (RR=0.88; 95% CI, 0.79–0.97) reduction in risk of stroke for each 10 g per day increment in dietary fiber intake. Moderate heterogeneity emerged in some of analyses, but disappeared after removing one study substantially contributing to the heterogeneity. Little evidence of publication bias was detected. Conclusion: Findings of this meta-analysis indicate a significant inverse dose-response relationship between dietary fiber intake and risk of stroke.

Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis. We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats. Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats. CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.

OBJECTIVE: We conducted this meta-analysis to compare the clinical outcomes of single-incision and multiple-incision video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer patients. METHODS: A literature search was conducted of the Cochrane Controlled Trials Register Databases, Medline, EMBASE, Web of Science databases, and Chinese Biomedical Literature Database. Eleven studies that compared single-incision VATS with multiple-incision VATS in the treatment of lung cancer were analyzed. Statistical analysis was carried out using RevMan 5.1 software. RESULTS: Eleven trials totaling 1273 patients were included. There were statistically significant differences in the duration of chest tube (standardized mean difference [SMD] = −0.42; 95% confidence interval [CI] [−0.78, −0.07], P < 0.02), hospital stays after surgery (SMD = −0.28; 95% CI [−0.41, −0.15], P < 0.0001), hospital stays after surgery in the subgroup analysis of lobectomy (SMD = −0.28; 95% CI [−0.42, −0.14], P < 0.0001), length of wound (P < 0.05), and pain visual analog scale (VAS) in the postoperative 1 day (SMD = −1.19; 95% CI [−1.94, −0.44], P = 0.002) between single-incision VATS group and multiple-incision VATS group. Compared with patients receiving multiple-incision VATS group, there were no statistically significant differences between the two groups with regard to the operative time (OT), blood loss (BL), rate of conversion to thoracotomy, and complication. CONCLUSION: Compared with multiple-incision VATS on the condition of same lymph nodes retrieved number, single-incision VATS reduced the length of wound, shortened the duration of chest tube, cut down the hospital stays after surgery, alleviated the pain VAS in the postoperative 1 day, did not significantly increase the OT and the BL in operation, and did not increase the rate of conversion to thoracotomy and complication.

Monitoring the stability of the Ronne Ice Shelf, particularly the calving event, is an integral and important part of the study of Antarctic ice sheet mass balance and sea-level rise. This paper presents the results of the analysis of the world’s largest iceberg (A-76 iceberg), which was formed during a calving event in the Ronne Ice Shelf (RIS) on May 13, 2020, and subsequently broke into three fragments (A-76A, A-76B, and A-76C icebergs). The iceberg development cycle, up to this point, including its formation, separation and drift, was observed and analyzed. The detailed development process of rifts associated with the detachment of the A-76 iceberg in front of RIS before calving was analyzed using remote sensing data from multiple sources (ERS, RADARSAT-1, ALOS PALSAR, Landsat-7, and Landsat-8). In addition, based on a total of 66 Sentinel-1 A/B Synthetic Aperture Radar (SAR) images acquired between May 13, 2021 and March 11, 2022, a multi-scale segmentation approach was applied to continuously track the drift path of A-76 icebergs, A-76A, A-76B, and A-76C. We calculated the average drift velocity of these icebergs and found that A-76C iceberg drifted the fastest, followed by A-76A, and A-76B, from May 30, 2021, to March 11, 2022. Future tracking of other iceberg parameters, such as area, thickness, freeboard, and volume, could help assess the melting rates of the icebergs.

AbstractBackgroundPopulation aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. MethodsThe frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. ResultsThe prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5′-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. ConclusionsProinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.

Fractures are an important indicator of ice shelf instability and predecessors of calving events. It is of great importance to identify fractures and understand the formation and propagation processes of fractures. However, automated methods of fracture identification also erroneously extract non‐fracture features, which are mixed with the automatically extracted fractures, negatively impacting the accuracy of the results. In this study, a framework for fracture extraction with glaciological property‐based constraints was proposed to extract fractures and filter out non‐fracture features. The extraction module consists of image preprocessing and linear feature extraction. The constraints were based on glaciological property analysis, including constraints based on physical properties of fractures and structural properties of ice shelves. The framework was applied to Mosaic of Antarctica and Landsat 8 Operational Land Imager images to extract fractures on the Filchner–Ronne Ice Shelf. The results suggest that most of the non‐fracture features were successfully filtered out, accounting for about half of all linear features. Upon comparison, it was found that the proposed method detected ∼97% of the rifts and ∼42% of the crevasses detected by manual extraction. The spatial pattern and formation mechanisms of the fractures were analyzed based on strain maps. The formation of crevasses is closely related to shear margin and longitudinal tension, while the large rifts near the ice shelf front are likely to be related to the strikes of lateral ice flow tributaries. The constraint strategy can be further improved by utilizing more glaciological properties to obtain more‐accurate fracture extraction. Plain Language Summary Ice shelf fracture is of great importance because it leads to ice shelf calving. Ice shelf calving will then accelerate ice loss in Antarctica and sea level rise. However, masses of non‐fracture features are mixed into automatic fracture extraction results. To deal with this problem, an extraction framework with constraints was proposed to filter out non‐fracture features. The constraints are based on the different patterns found in fractures and non‐fractures. The framework was applied to two imagery sets of the Filchner–Ronne Ice Shelf. The results suggest that most of the non‐fracture features were successfully filtered out, which account for about half of the extraction results. The automatic extraction identified ∼97% of rifts and ∼42% of the crevasses of the manual extraction results. Based on the analysis of the fracture map, crevasse formation is mostly caused by shear margin and longitudinal tension, while the large rifts near the ice shelf front may be caused by strikes of lateral ice flow tributaries. The constraint strategy can be further improved by utilizing more glaciological properties to more accurately extract features. Key Points Universal glaciological constraints are applied to filter out non‐fracture features, which account for half of the extraction results Rift extraction accuracy for Mosaic of Antarctica and Operational Land Imager reached 96% and 99%, respectively The extracted fractures from the Filchner–Ronne Ice Shelf are densest in areas with high strain rates