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Static stripe order is detrimental to superconductivity. Yet, it has been proposed that transverse stripe fluctuations may enhance the inter-stripe Josephson coupling and thus promote superconductivity. Direct experimental studies of stripe dynamics, however, remain difficult. From a strong-coupling perspective, transverse stripe fluctuations are realized in the form of dynamic "kinks"—sideways shifting stripe sections. Here, we show how modest uniaxial pressure tuning reorganizes directional kink alignment. Our starting point is La1.88Sr0.12CuO4 where transverse kink ordering results in a rotation of stripe order away from the crystal axis. Application of mild uniaxial pressure changes the ordering pattern and pins the stripe order to the crystal axis. This reordering occurs at a much weaker pressure than that to detwin the stripe domains and suggests a rather weak transverse stripe stiffness. Weak spatial stiffness and transverse quantum fluctuations are likely key prerequisites for stripes to coexist with superconductivity. Transverse stripe order fluctuations may promote superconductivity, but experimental verifications remain difficult. Here, the authors report that a mild uniaxial pressure changes the ordering pattern and pins the stripe order to the crystal axis in La1.88Sr0.12CuO4. [ABSTRACT FROM AUTHOR]

Static stripe order is detrimental to superconductivity. Yet, it has been proposed that transverse stripe fluctuations may enhance the inter-stripe Josephson coupling and thus promote superconductivity. Direct experimental studies of stripe dynamics, however, remain difficult. From a strong-coupling perspective, transverse stripe fluctuations are realized in the form of dynamic "kinks"—sideways shifting stripe sections. Here, we show how modest uniaxial pressure tuning reorganizes directional kink alignment. Our starting point is La1.88Sr0.12CuO4 where transverse kink ordering results in a rotation of stripe order away from the crystal axis. Application of mild uniaxial pressure changes the ordering pattern and pins the stripe order to the crystal axis. This reordering occurs at a much weaker pressure than that to detwin the stripe domains and suggests a rather weak transverse stripe stiffness. Weak spatial stiffness and transverse quantum fluctuations are likely key prerequisites for stripes to coexist with superconductivity. Transverse stripe order fluctuations may promote superconductivity, but experimental verifications remain difficult. Here, the authors report that a mild uniaxial pressure changes the ordering pattern and pins the stripe order to the crystal axis in La1.88Sr0.12CuO4. [ABSTRACT FROM AUTHOR]

Increasing resistance of Pseudomonas aeruginosa (P. aeruginosa) to conventional treatments demands the search for novel therapeutic strategies. In this study, the antimicrobial activity of dehydroleucodine (DhL), a sesquiterpene lactone obtained from Artemisia (A.) douglasiana, was screened against several pathogenic virulence effectors of P. aeruginosa. In vitro, minimum inhibitory concentration of DhL was determined against P. aeruginosa strains PAO1, PA103, PA14, and multidrug resistant clinical strain, CDN118. Results showed that DhL was active against each strain where PAO1 and PA103 showed higher susceptibility (MIC 0.48 mg/mL) as compared to PA14 (MIC 0.96 mg/mL) and CDN118 (MIC 0.98 mg/mL). Also, when PAO1 strain was grown in the presence of DhL (MIC50, 0.12 mg/mL), a delay in the generation time was noticed along with significant inhibition of secretory protease and elastase activities, interruption in biofilm attachment phase in a stationary culture, and a significant decline in Type III effector ExoS. At MIC50, DhL treatment increased the sensitivity of P. aeruginosa towards potent antibiotics. Furthermore, treatment of P. aeruginosa with DhL prevented toxin-induced apoptosis in macrophages. These observations suggest that DhL activity was at the bacterial transcriptional level. Hence, antimicrobial activity of DhL may serve as leads in the development of new anti-Pseudomonas pharmaceuticals. [ABSTRACT FROM AUTHOR]

Utilization of agricultural waste to produce biochar has already proven to be an efficient method for transforming waste into valuable resources. In this study, rubber seed shell (RSS) was utilized to prepare two biochar samples via an in-house built reactor (RSSBC-1) and a pyrolysis reactor (RSSBC-2) under identical conditions (600 °C for 3 h at a heating rate of 10 °C per min). A comprehensive characterization of the prepared biochar samples was carried out to reveal the reactor effect on the biochar properties. For this, proximate and ultimate analyses were carried out which estimated the carbon stability, polarity, and aromaticity of the biochar samples. For RSSBC-1, C and N content were higher, whereas H and O content were higher for RSSBC-2, as found from elemental, EDX, and XPS analyses. Point of zero charge (PZC) values of 7.65 and 6.14 for RSSBC-1 and RSSBC-2, respectively, emphasized the importance of pH in the removal of ionic contaminants. Furthermore, the superiority of RSSBC-1 in terms of specific surface area of 336.02 m 2 g -1 compared to 299.09 m 2 g -1 of RSSBC-2 was articulated by BET analysis. XPS and FESEM analyses revealed the chemical state of surface elements and surface morphology, respectively of the biochar samples. XRD patterns assured the amorphous nature of biochar samples, and functional groups were well depicted by FTIR analysis. DLS showed a larger average hydrodynamic diameter for RSSBC-2 (248.68 nm) with a zeta potential of -14.91 mV compared to RSSBC-1 (115.23 nm) with a heterogeneous charge distribution (-16.72 mV and +37.61 mV). TGA analysis revealed the thermal stability of both biochar samples. Overall, the results explicitly depict a distinction in the properties of biochar samples prepared in two different reactors, where RSSBC-1, with its superior properties suggests the in-house built reactor as a promising alternative to expensive pyrolytic reactors for waste valorization., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Vasculogenic mimicry (VM), an endothelial cell-independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin-5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM- cohorts. The expression pattern of laminin-5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan-Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin-5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin-5γ2 and MMP2 in VM+ cohorts compared with the VM- ones. Furthermore, co-expression of VM and laminin-5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin-5γ2 double-positive cohort displayed a significantly poorer disease-free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin-5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin-5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin-5γ2 coordination emerges as a critical prognostic biomarker for OSCC., (© 2022 Company of the International Journal of Experimental Pathology (CIJEP).)

Purpose: To study the association of gastric cancer with various clinicopathological traits in eastern India which can be used as an important factor for further analysis, understanding of the diseases and amelioration of patients., Methods: The retrospective study includes the patients who underwent subtotal or total gastrectomy from surgical oncology department of Chittaranjan National Cancer Institute (hospital) of West Bengal, India between 2014 and 2018. The study includes 751 gastric cancer patients from Chittaranjan National Cancer Institute. We used electronic hospital records to collect data on various clinical parameters and other information. We used Microsoft Office Excel 2007 spreadsheets for the statistical analyses., Results: Incidence of gastric cancer is associated with mid age (40-59 years) group male patients and lymph node metastasis. Frequency of gastric cancer is highest in the antrum (42.21%). Of the mid age group gastric cancer patients, 35.02% were having much high risk of developing diffused type of adenocarcinoma (P < 0.00001). Tobacco intake in form of smoking was found as an important risk factor in gastric cancer development with risk ratio and odds ratio of 1.18 and 3.14 respectively., Conclusion: Collectively, the results of the present study confirm that incidence of diffused type of gastric cancer is increasing as an alarming rate in mid age group male patients and tobacco intake in the form of smoking as an independent risk factor for this type of cancer in eastern India. This result can be used to manage gastric carcinoma in future prospective clinical studies and in patient's improvement., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Ascorbic acid (vitamin C) is critical for Schwann cells to myelinate peripheral nerve axons during development and remyelination after injury. However, its exact mechanism remains elusive. Vitamin C is a dietary nutrient that was recently discovered to promote active DNA demethylation. Schwann cell myelination is characterized by global DNA demethylation in vivo and may therefore be regulated by vitamin C. We found that vitamin C induces a massive transcriptomic shift (n = 3,848 genes) in primary cultured Schwann cells while simultaneously producing a global increase in genomic 5-hydroxymethylcytosine (5hmC), a DNA demethylation intermediate which regulates transcription. Vitamin C up-regulates 10 pro-myelinating genes which exhibit elevated 5hmC content in both the promoter and gene body regions of these loci following treatment. Using a mouse model of human vitamin C metabolism, we found that maternal dietary vitamin C deficiency causes peripheral nerve hypomyelination throughout early development in resulting offspring. Additionally, dietary vitamin C intake regulates the expression of myelin-related proteins such as periaxin (PRX) and myelin basic protein (MBP) during development and remyelination after injury in mice. Taken together, these results suggest that vitamin C cooperatively promotes myelination through 1) increased DNA demethylation and transcription of pro-myelinating genes, and 2) its known role in stabilizing collagen helices to form the basal lamina that is necessary for myelination., (© 2020 International Society for Neurochemistry.)

A high incidence of oral squamous cell carcinoma (OSCC) is observed in South-East Asian countries due to addictions such as chewing tobacco. Local invasion and distant metastases are primary causes of poor prognosis in OSCC. This study aimed to understand the alterations in metastasis biomarkers, such as stromal cell-derived factor-1α (SDF-1 or SDF1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4), in OSCC patient samples that were stratified based on the history of addiction to chewing tobacco. Targeted immunohistochemical staining and Western blotting were performed on primary tumour and metastatic lymph node (LN) tissues in parallel. Overexpression of hepatocyte growth factor (HGF), activated form of its cognate receptor tyrosine kinase, c-Met (p-Met), GRB2-associated-binding protein 1 (Gab1), phospho-protein kinase B (pAkt), nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2) were observed in primary tumour and metastatic lymph nodes in both chewer and non-chewer cohorts. Variance analysis showed significant positive correlation between them (P < .0001) indicating upregulation of these biomarkers upon ligand-induced activation of c-Met in both tobacco chewers and non-chewers. Significantly higher expressions of SDF1α and CXCR4 were observed in both primary tumours and metastatic lymph nodes of tobacco chewers (P < .0001) and coincided with overexpressed HGF. In contrast, no significant correlation was observed between expression of HGF and that of SDF1α and CXCR4 in non-chewers. Together, our findings provide important insights into the association of HGF/c-Met and the SDF1α/CXCR4 axis in lymph node metastasis and to an aetiological link with the habit of chewing tobacco., (© 2021 Company of the International Journal of Experimental Pathology (CIJEP).)

Rationale: The clinical use of PI3K inhibitors, such as buparlisib, has been plagued with toxicity at effective doses. The aim of this study is to determine if vitamin C, a potent epigenetic regulator, can improve the therapeutic outcome and reduce the dose of buparlisib in treating PIK3CA -mutated triple negative breast cancer (TNBC). Methods: The response of TNBC cells to buparlisib was assessed by EC 50 measurements, apoptosis assay, clonogenic assay, and xenograft assay in mice. Molecular approaches including Western blot, immunofluorescence, RNA sequencing, and gene silencing were utilized as experimental tools. Results: Treatment with buparlisib at lower doses, along with vitamin C, induced apoptosis and inhibited the growth of TNBC cells in vitro . Vitamin C via oral delivery rendered a sub-therapeutic dose of buparlisib able to inhibit TNBC xenograft growth and to markedly block metastasis in mice. We discovered that buparlisib and vitamin C coordinately reduced histone H3K4 methylation by enhancing the nuclear translocation of demethylase, KDM5, and by serving as a cofactor to promote KDM5-mediated H3K4 demethylation. The expression of genes in the PI3K pathway, such as AKT2 and mTOR, was suppressed by vitamin C in a KDM5-dependent manner. Vitamin C and buparlisib cooperatively blocked AKT phosphorylation. Inhibition of KDM5 largely abolished the effect of vitamin C on the response of TNBC cells to buparlisib. Additionally, vitamin C and buparlisib co-treatment changed the expression of genes, including PCNA and FILIP1L, which are critical to cancer growth and metastasis. Conclusion: Vitamin C can be used to reduce the dosage of buparlisib needed to produce a therapeutic effect, which could potentially ease the dose-dependent side effects in patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Nikolsky's sign has been a very useful diagnostic tool in cases of skin disorders like pemphigus, toxic epidermal necrolysis, etc., The sign is demonstrated when lateral pressure is applied on the border of an intact blister, which results in the dislodgment of the normal epidermis and extension of the blister., Competing Interests: There are no conflicts of interest., (Copyright: © Journal of Family Medicine and Primary Care.)

Vitamin C supplementation has been shown to decrease triple-negative breast cancer (TNBC) metastasis. However, the molecular mechanism whereby vitamin C inhibits metastasis remains elusive. It has been postulated that vitamin C reduces the levels of HIF-1α, the master regulator of metastasis, by promoting its hydroxylation and degradation. Here, we show that vitamin C at 100 µM, a concentration achievable in the plasma in vivo by oral administration, blocks TNBC cell migration and invasion in vitro. The protein level of HIF-1α remains largely unchanged in cultured TNBC cells and xenografts, partially due to its upregulated transcription by vitamin C, suggesting that HIF-1α unlikely mediates the action of vitamin C on metastasis. Vitamin C treatment upregulates the expression of synaptopodin 2 and downregulates the expression of the transcription coactivator YAP1 , both genes in the Hippo pathway. The changes in SYNPO2 and YAP1 expression were subsequently validated at mRNA and protein levels in cultured TNBC cells and xenografts. Further experiments showed that vitamin C treatment inhibits F-actin assembly and lamellipodia formation, which correlates with the changes in SYNPO2 and YAP1 expression. Overall, these results suggest that vitamin C inhibits TNBC metastasis by affecting the expression of SYNPO2 and YAP1 . Vitamin C may thus have a potential role in the prevention and treatment of TNBC metastasis.

Background/aim: The aim of this pilot study was to perform morphometric analysis of the foramen magnum (FM) using cone-beam computed tomography (CBCT)., Materials and Methods: This study included CBCT images of 120 individuals (60 males and 60 females). The sagittal and transverse diameters and circumference of the FM were measured. The data were statistically analyzed with Chi-square and t -tests to assess the level of significance for sex and age., Results: The means of its sagittal and transverse diameters and also circumference were higher in males than in females. Statistically significant differences were found between transverse and circumference in case of males and females for all variables ( P < 0.05). No statistically significant difference ( P > 0.05) was found in sagittal diameter and age groups for all variables., Conclusion: CBCT images can provide valuable information regarding FM and the measurements of its sagittal and transvers diameters and also its circumference may be reliably used for sexual dimorphism in anthropometric analysis and forensic medicine., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Forensic Dental Sciences.)

Background: Bromodomain and extra-terminal inhibitors (BETi) have shown efficacy for the treatment of aggressive triple negative breast cancer (TNBC). However, BETi are plagued by a narrow therapeutic window as manifested by severe toxicities at effective doses. Therefore, it is a limitation to their clinical implementation in patient care., Methods: The impact of vitamin C on the efficacy of small compounds including BETi was assessed by high-throughput screening. Co-treatment of TNBC by BETi especially JQ1 and vitamin C was evaluated in vitro and in vivo., Findings: High-throughput screening revealed that vitamin C improves the efficacy of a number of structurally-unrelated BETi including JQ1, I-BET762, I-BET151, and CPI-203 in treating TNBC cells. The synergy between BETi and vitamin C is due to suppressed histone acetylation (H3ac and H4ac), which is in turn caused by upregulated histone deacetylase 1 (HDAC1) expression upon vitamin C addition. Treatment with JQ1 at lower doses together with vitamin C induces apoptosis and inhibits the clonogenic ability of cultured TNBC cells. Oral vitamin C supplementation renders a sub-therapeutic dose of JQ1 able to inhibit human TNBC xenograft growth and metastasis in mice., Interpretation: Vitamin C expands the therapeutic window of BETi by sensitizing TNBC to BETi. Using vitamin C as a co-treatment, lower doses of BETi could be used to achieve an increased therapeutic index in patients, which will translate to a reduced side effect profile. FUND: University of Miami Sylvester Comprehensive Cancer Center, Bankhead Coley Cancer Research program (7BC10), Flight Attendant Medical Research Institute, and NIH R21CA191668 (to GW) and 1R56AG061911 (to CW and CHV)., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Pemphigus is comprised of a group of life-threatening autoimmune diseases that is characterized by circulating IgG antibodies targeting several types of keratinocyte antigens. After introduction of systemic steroids, survival has improved dramatically. However, mortality and morbidity were still very high due to side effects of steroids. Pulse therapy is defined as discontinuous/intermittent intravenous infusion of very high doses of corticosteroids along with certain immunosuppressive agents over a short period. This therapy was introduced to minimize the side effects of conventional corticosteroid therapy. The target is to achieve a faster response and stronger efficacy and to decrease the need for long-term use of systemic corticosteroids. As a result, this therapy has gained its popularity since three decades. The purpose of this article is to review the various available pulse therapy regimens with dosage, indications and contraindications and side effects., Competing Interests: There are no conflicts of interest.

Purpose: To investigate the impact of ascorbate, via DNA hydroxymethylation, on VEGF expression in retinal pigment epithelial (RPE) cells., Methods: Dot-blot and hydroxymethylated DNA immunoprecipitation sequencing were applied to evaluate the impact of ascorbate on DNA hydroxymethylation in ARPE-19 cells. RNA sequencing (RNA-seq) was carried out to analyze the transcriptome. Quantitative RT-PCR and ELISA were conducted to examine the transcription and secretion of VEGF from cultured cells. Primary human fetal RPE cells and RPE-J cells were used to verify the effect of ascorbate on VEGF expression. ELISA was used to measure VEGF in the vitreous humor of Gulo-/- mice, which, like humans, cannot synthesize ascorbate de novo., Results: Treatment with ascorbate (50 μM) promoted 5-hydroxymethycytosine (5hmC) generation and changed the genome-wide profiles of 5hmC in ARPE-19 cells. Ascorbate also caused a dramatic shift in the transcriptome-3186 differential transcripts, of which 69.3% are correlated with altered 5hmC in promoters or gene bodies. One of the most downregulated genes was VEGFA, which encodes the VEGF protein. The suppression of VEGF by ascorbate is independent of hypoxia-inducible factor 1-alpha (HIF-1α) but correlates with increased 5hmC in the gene body. The decreased transcription and secretion of VEGF by ascorbate were verified in primary human fetal RPE cells. Furthermore, adding ascorbate in the diet for Gulo-/- mice resulted in decreased levels of VEGF in the RPE/choroid and vitreous humor., Conclusions: Ascorbate inhibits VEGF expression in RPE cells likely via DNA hydroxymethylation. Thus, ascorbate could be implicated in the prevention or treatment of diseases such as age-related macular degeneration (AMD).

Neurite orientation dispersion and density imaging (NODDI), a MRI multi-shell diffusion technique, has offered new insights for the study of microstructural changes in neurodegenerative diseases. Mainly, the present study aimed to determine the connection between NODDI-derived parameters and changes in white matter (WM) abnormalities at early stages of amyotrophic lateral sclerosis (ALS). Spinal cords from ALS mice (G93A-SOD1 mice) were scanned in a Bruker Avance III HD 17.6T magnet. Fluorescent axonal-tagged mice (YFP, G93A-SOD1 mice) were used for quantitative histological analysis. NODDI showed a decrease in intra-cellular volume fraction (-24%) and increases in orientation dispersion index (+35%) and isotropic volume fraction (+33%). In addition, histoathological results demonstrated a reductions in axonal area (-11%) and myelin content (-29%). A histological decrease in WM intra-axonal space (-71%) and an increase in the extra-axonal compartment (+22%) were also detected. Our studies demonstrate that NODDI may be a suitable technique for detecting presymptomatic spinal cord WM microstructural degeneration in ALS.