Protective Effect of Curcumin on the Tight Junction Integrity and Cellular Senescence in Human Retinal Pigment Epithelium of Early Diabetic Retinopathy.

Diabetic retinopathy (DR) is a secondary complication of diabetes that can lead to visual impairment and blindness. The retinal pigment epithelium (RPE) is a monolayer of pigment cells that forms the blood-retinal barrier (BRB) via tight junction (TJ) proteins and plays a crucial role in the physiological function of the retina. Hyperglycemia induces RPE death and BRB breakdown, which accelerates the process of DR. Curcumin, an active extract of Curcuma longa , has anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective properties. However, the effect of Curcumin on the BRB under high glucose conditions remains unknown. This study aimed to investigate the protective effects of Curcumin on RPE physiology in vitro and in vivo . Curcumin significantly alleviated cell viability inhibition under high glucose conditions. Moreover, high glucose reduced extracellular signal-regulated kinase and Akt pathways activation to diminish RPE cell growth but reversed by Curcumin treatment. Curcumin protected not only TJ integrity but also retinoid regeneration through TJ proteins and isomerase modulation in diabetic retina. Furthermore, Curcumin decreased the expression of angiogenic factor to inhibit retinal neovascularization. Finally, Curcumin treatment markedly reduced apoptosis during hyperglycemia. In conclusion, Curcumin can alleviate the progression of DR by promoting RPE survival, TJ integrity, retinoid isomerase activity, RPE senescence inhibition, and neovascularization. Therefore, Curcumin exhibits high potential for use as a therapeutic agent for early DR.

Inflammasome functional activities in B lymphocytes.

Studies in animal models and human subjects have shown that, in addition to their implication in innate immunity, inflammasomes also can play a role in adaptive immunity. However, the contribution of the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway to adaptive immunity remains incompletely explored. Here, we show that NLRP3 plays an important role in different facets of B cell functions, including proliferation, antibody production, and secretion of inflammatory and anti-inflammatory cytokines. When exposed to B cell receptor engagement, Toll-like receptor activation, stimulation in conditions that mimic T cell-dependent responses, or NLRP3 activation, B cells manifest disparate responses and produce different cytokine patterns critical for modulating innate and adaptive immunity, indicating that the cytokines produced serve a critical link between the early innate immune response and the delayed adaptive immunity. Importantly, genetic ablation of nlrp3 reduced the inflammasome-mediated functions of B cells. We propose that, in the absence of other cell types, the potential of B lymphocytes to respond to NLRP3 engagement enables them to initiate inflammatory cascades through recruitment of other cell subsets, such as macrophages and neutrophils. Since NLRP3 activation of B cells is not followed by pyroptosis, even in the presence of a basal caspase-1 activity, this pathway acts as a bridge that optimizes interactions between the innate and adoptive branches of the immune response.

Protocol for isolating small cytosolic dsDNA from cultured murine cells.

We recently identified a class of small cytosolic double-stranded DNA (scDNA) approximately 20-40 bp in size in human and mouse cells. Here, we present a protocol for scDNA isolation from cultured murine cells. We describe steps for cytosolic compartment separation, DNA isolation in the cytosolic fraction using phenol-chloroform extraction, and ethanol precipitation. We then detail procedures for denaturing purified cytosolic DNA through urea polyacrylamide gel electrophoresis and obtaining scDNA in the cytosolic DNA fraction via gel purification. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Basal actomyosin pulses expand epithelium coordinating cell flattening and tissue elongation.

Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. However, during cell expansion under mechanical stress, actomyosin networks are strengthened and polarized to relax stress. Thus, cells face a conflicting situation between the enhanced actomyosin contractile properties and the expansion behaviour of the cell or tissue. To address this paradoxical situation, we study late Drosophila oogenesis and reveal an unusual epithelial expansion wave behaviour. Mechanistically, Rac1 and Rho1 integrate basal pulsatile actomyosin networks with ruffles and focal adhesions to increase and then stabilize basal area of epithelial cells allowing their flattening and elongation. This epithelial expansion behaviour bridges cell changes to oocyte growth and extension, while oocyte growth in turn deforms the epithelium to drive cell spreading. Basal pulsatile actomyosin networks exhibit non-contractile mechanics, non-linear structures and F-actin/Myosin-II spatiotemporal signal separation, implicating unreported expanding properties. Biophysical modelling incorporating these expanding properties well simulates epithelial cell expansion waves. Our work thus highlights actomyosin expanding properties as a key mechanism driving tissue morphogenesis.

Far-Field Petahertz Sampling of Plasmonic Fields.

The response of metal nanostructures to optical excitation leads to localized surface plasmon (LSP) generation with nanoscale field confinement driving applications in, for example, quantum optics and nanophotonics. Field sampling in the terahertz domain has had a tremendous impact on the ability to trace such collective excitations. Here, we extend such capabilities and introduce direct sampling of LSPs in a more relevant petahertz domain. The method allows to measure the LSP field in arbitrary nanostructures with subcycle precision. We demonstrate the technique for colloidal nanoparticles and compare the results to finite-difference time-domain calculations, which show that the build-up and dephasing of the plasmonic excitation can be resolved. Furthermore, we observe a reshaping of the spectral phase of the few-cycle pulse, and we demonstrate ad-hoc pulse shaping by tailoring the plasmonic sample. The methodology can be extended to single nanosystems and applied in exploring subcycle, attosecond phenomena.

Nighttime color constancy using robust gray pixels.

Color constancy is a basic step for achieving stable color perception in both biological visual systems and the image signal processing (ISP) pipeline of cameras. So far, there have been numerous computational models of color constancy that focus on scenes under normal light conditions but are less concerned with nighttime scenes. Compared with daytime scenes, nighttime scenes usually suffer from relatively higher-level noise and insufficient lighting, which usually degrade the performance of color constancy methods designed for scenes under normal light. In addition, there is a lack of nighttime color constancy datasets, limiting the development of relevant methods. In this paper, based on the gray-pixel-based color constancy methods, we propose a robust gray pixel (RGP) detection method by carefully designing the computation of illuminant-invariant measures (IIMs) from a given color-biased nighttime image. In addition, to evaluate the proposed method, a new dataset that contains 513 nighttime images and corresponding ground-truth illuminants was collected. We believe this dataset is a useful supplement to the field of color constancy. Finally, experimental results show that the proposed method achieves superior performance to statistics-based methods. In addition, the proposed method was also compared with recent deep-learning methods for nighttime color constancy, and the results show the method's advantages in cross-validation among different datasets.

Retinal Layer Segmentation in OCT Images With Boundary Regression and Feature Polarization.

The geometry of retinal layers is an important imaging feature for the diagnosis of some ophthalmic diseases. In recent years, retinal layer segmentation methods for optical coherence tomography (OCT) images have emerged one after another, and huge progress has been achieved. However, challenges due to interference factors such as noise, blurring, fundus effusion, and tissue artifacts remain in existing methods, primarily manifesting as intra-layer false positives and inter-layer boundary deviation. To solve these problems, we propose a method called Tightly combined Cross-Convolution and Transformer with Boundary regression and feature Polarization (TCCT-BP). This method uses a hybrid architecture of CNN and lightweight Transformer to improve the perception of retinal layers. In addition, a feature grouping and sampling method and the corresponding polarization loss function are designed to maximize the differentiation of the feature vectors of different retinal layers, and a boundary regression loss function is devised to constrain the retinal boundary distribution for a better fit to the ground truth. Extensive experiments on four benchmark datasets demonstrate that the proposed method achieves state-of-the-art performance in dealing with problems of false positives and boundary distortion. The proposed method ranked first in the OCT Layer Segmentation task of GOALS challenge held by MICCAI 2022. The source code is available at https://www.github.com/tyb311/TCCT.

Upregulation of CELSR1 expression promotes ovarian cancer cell proliferation, migration, and invasion.

Cadherin epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an epithelial sheet or multicellular clusters. CELSR1 has been suggested to play a role in glioma, breast cancer, and chronic lymphocytic leukemia development; however, whether it has a role in the pathogenesis of ovarian cancer remains unknown. The aim of this study was to determine the role of CELSR1 in ovarian cancer and elucidate its underlying molecular mechanisms. By analyzing gene expression data downloaded from the Cancer Genome Atlas database, we found that CELSR1 expression was upregulated in ovarian cancer tissues compared to that in normal ovarian tissues. High CELSR1 expression levels were associated with poor prognosis in patients with ovarian cancer. Cell proliferation, scratch, and transwell assays revealed that CELSR1 promoted the proliferation, migration, and invasion of ovarian cancer cells in vitro. In addition, transcriptome sequencing analysis revealed that CELSR1 knockdown in T29H cells resulted in the dysregulation of the expression of 1320 genes. Further analysis revealed that genes involved in proliferation- and migration-associated signaling pathways were regulated by CELSR1. Our study demonstrates that CELSR1 is highly expressed in ovarian cancer cells and regulates their proliferation and migration, suggesting its potential as a diagnostic marker and therapeutic target.

Mutual communication between radiosensitive and radioresistant esophageal cancer cells modulates their radiosensitivity.

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.

Communication between small cytosolic dsDNA and autophagy inhibits CGAS (cyclic GMP-AMP synthase) activation.

The CGAS (cyclic GMP-AMP synthase)-STING1 (stimulator of interferon response cGAMP interactor 1) pathway is an important innate immune pathway that induces proinflammatory cytokine production following stimulation with dsDNA > 45 bp. We recently identified a class of ~ 20-40 bp small cytosolic dsDNA (scDNA) that blocks CGAS-STING1 activation. In this punctum, we discuss the mechanism underlying the inhibition of CGAS-STING1 activation via scDNA. scDNA binds to CGAS but cannot activate its enzymatic activity. It competes with dsDNA > 45 bp for binding with CGAS to inhibit CGAS-STING1 activation. Moreover, scDNA activates macroautophagy/autophagy and induces the autophagic degradation of STING1 and long dsDNA. Autophagy then increases scDNA levels, driving a feedback loop that accelerates the degradation of STING1 and long cytosolic dsDNA. These findings reveal that mutual communication between scDNA and autophagy inhibits CGAS-STING1 activation following stimulation with dsDNA > 45 bp.

Postoperative urinary leakage after bilateral totally extraperitoneal herniorrhaphy in a patient with a healed cystostomy and appendectomy: A case report.

We report a case of postoperative urinary leakage after bilateral laparoscopic totally extraperitoneal (TEP) herniorrhaphy. A man in his upper 80s with a healed cystostomy and appendectomy underwent bilateral TEP herniorrhaphy. Urinary leakage was noted by ultrasound examination 4 days after bilateral TEP. Cystography and computed tomography conclusively confirmed a 6-mm extraperitoneal fistula at the site of the previous cystostomy. The fistula involved the anterior bladder wall and was associated with an extended urinoma. The patient was treated by indwelling catheterization using a Foley catheter and repeated ultrasound-guided puncture and aspiration of the inguinal effusion at the bedside. The patient was completely healed 69 days after the operation with no mesh infection or bladder dysfunction. We believe that urinary leakage is possible after TEP herniorrhaphy in patients with a healed suprapubic cystostomy. Therefore, indwelling catheterization using a Foley catheter should be implemented before surgery, and the Foley catheter can be removed within 1 week after surgery if no postoperative urinary leakage is observed. A history of suprapubic cystotomy should not be regarded as a contraindication for TEP surgery. This is the first report of urinary leakage after bilateral TEP herniorrhaphy in a patient with a healed cystostomy and appendectomy.

Diagnostic value of preoperative examination for evaluating margin status in breast cancer.

BACKGROUND: A positive resection margin is a major risk factor for local breast cancer recurrence after breast-conserving surgery (BCS). Preoperative imaging examinations are frequently employed to assess the surgical margin. AIM: To investigate the role and value of preoperative imaging examinations [magnetic resonance imaging (MRI), molybdenum target, and ultrasound] in evaluating margins for BCS. METHODS: A retrospective study was conducted on 323 breast cancer patients who met the criteria for BCS and consented to the procedure from January 2014 to July 2021. The study gathered preoperative imaging data (MRI, ultrasound, and molybdenum target examination) and intraoperative and postoperative pathological information. Based on their BCS outcomes, patients were categorized into positive and negative margin groups. Subsequently, the patients were randomly split into a training set (226 patients, approximately 70%) and a validation set (97 patients, approximately 30%). The imaging and pathological information was analyzed and summarized using R software. Non-conditional logistic regression and LASSO regression were conducted in the validation set to identify factors that might influence the failure of BCS. A column chart was generated and applied to the validation set to examine the relationship between pathological margin range and prognosis. This study aims to identify the risk factors associated with failure in BCS. RESULTS: The multivariate non-conditional logistic regression analysis demonstrated that various factors raise the risk of positive margins following BCS. These factors comprise non-mass enhancement (NME) on dynamic contrast-enhanced MRI, multiple focal vascular signs around the lesion on MRI, tumor size exceeding 2 cm, type III time-signal intensity curve, indistinct margins on molybdenum target examination, unclear margins on ultrasound examination, and estrogen receptor (ER) positivity in immunohistochemistry. LASSO regression was additionally employed in this study to identify four predictive factors for the model: ER, molybdenum target tumor type (MT Xmd Shape), maximum intensity projection imaging feature, and lesion type on MRI. The model constructed with these predictive factors exhibited strong consistency with the real-world scenario in both the training set and validation set. Particularly, the outcomes of the column chart model accurately predicted the likelihood of positive margins in BCS. CONCLUSION: The proposed column chart model effectively predicts the success of BCS for breast cancer. The model utilizes preoperative ultrasound, molybdenum target, MRI, and core needle biopsy pathology evaluation results, all of which align with the real-world scenario. Hence, our model can offer dependable guidance for clinical decision-making concerning BCS.

Downregulation of VEGFR2 signaling by cedrol abrogates VEGF­driven angiogenesis and proliferation of glioblastoma cells through AKT/P70S6K and MAPK/ERK1/2 pathways.

Cedrol is a sesquiterpene alcohol isolated from Cedrus atlantica, which has been traditionally used in aromatherapy and has anticancer, antibacterial and antihyperalgesic effects. One characteristic of glioblastoma (GB) is the overexpression of vascular endothelial growth factor (VEGF), which induces a high degree of angiogenesis. Although previous studies have reported that cedrol inhibits GB growth by inducing DNA damage, cell cycle arrest and apoptosis, its role in angiogenesis remains unclear. The aim of the present study was to investigate the effects of cedrol on VEGF-induced angiogenesis of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 0-112 µM cedrol and 20 ng/ml VEGF for 0-24 h, and then anti-angiogenic activation of cedrol was determined by MTT assay, wound healing assay, Boyden chamber assay, tube formation assay, semi-quantitative reverse transcription-PCR and western blotting. These results demonstrated that cedrol treatment inhibited VEGF-induced cell proliferation, migration and invasion in HUVECs. Furthermore, cedrol prevented VEGF and DBTRG-05MG GB cells from inducing capillary-like tube formation in HUVECs and decreased the number of branch points formed. Moreover, cedrol downregulated the phosphorylation of VEGF receptor 2 (VEGFR2) and the expression levels of its downstream mediators AKT, ERK, VCAM-1, ICAM-1 and MMP-9 in HUVECs and DBTRG-05MG cells. Taken together, these results demonstrated that cedrol exerts anti-angiogenic effects by blocking VEGFR2 signaling, and thus could be developed into health products or therapeutic agents for the prevention or treatment of cancer and angiogenesis-related diseases in the future.

Small cytosolic double-stranded DNA represses cyclic GMP-AMP synthase activation and induces autophagy.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.

Upregulation of FAM50A promotes cancer development.

FAM50A encodes a nuclear protein involved in mRNA processing; however, its role in cancer development remains unclear. Herein, we conducted an integrative pan-cancer analysis using The Cancer Genome Atlas, Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium databases. Based on the gene expression data from TCGA and GTEx databases, we compared FAM50A mRNA levels in 33 types of human cancer tissues to those in corresponding normal tissues and found that FAM50A mRNA level was upregulated in 20 of the 33 types of common cancer tissues. Then, we compared the DNA methylation status of the FAM50A promoter in tumor tissues to that in corresponding normal tissues. FAM50A upregulation was accompanied by promoter hypomethylation in 8 of the 20 types of tumor tissues, suggesting that promoter hypomethylation contributes to the upregulation of FAM50A in these cancer tissues. Elevated FAM50A expression in 10 types of cancer tissues was associated with poor prognosis in patients with cancer. FAM50A expression was positively correlated with CD4+ T-lymphocyte and dendritic cell infiltration in cancer tissues but was negatively correlated with CD8+ T-cell infiltration in cancer tissues. FAM50A knockdown caused DNA damage, induced interferon beta and interleukin-6 expression, and repressed the proliferation, invasion, and migration of cancer cells. Our findings indicate that FAM50A might be useful in cancer detection, reveal insights into its role in cancer development, and may contribute to the development of cancer diagnostics and treatments.

Angelica sinensis extract induces telomere dysfunction, cell cycle arrest, and mitochondria-mediated apoptosis in human glioblastoma cells.

Glioblastoma (GB) is one of the most aggressive and malignant tumors of the central nervous system. Conventional treatment for GB requires surgical resection followed by radiotherapy combined with temozolomide chemotherapy; however, the median survival time is only 12-15 months. Angelica sinensis Radix (AS) is commonly used as a traditional medicinal herb or a food/dietary supplement in Asia, Europe, and North America. This study aimed to investigate the effect of AS-acetone extract (AS-A) on the progression of GB and the potential mechanisms underlying its effects. The results indicated that AS-A used in this study showed potency in growth inhibition of GB cells and reduction of telomerase activity. In addition, AS-A blocked the cell cycle at the G0/G1 phase by regulating the expression of p53 and p16. Furthermore, apoptotic morphology, such as chromatin condensation, DNA fragmentation, and apoptotic bodies, was observed in AS-A-treated cells, induced by the activation of the mitochondria-mediated pathway. In an animal study, AS-A reduced tumor volume and prolonged lifespans of mice, with no significant changes in body weight or obvious organ toxicity. This study confirmed the anticancer effects of AS-A by inhibiting cell proliferation, reducing telomerase activity, altering cell cycle progression, and inducing apoptosis. These findings suggest that AS-A has great potential for development as a novel agent or dietary supplement against GB.

The alleviation effects of n-butylidenephthalide on apoptosis, senescence, and tight junction impairment of retinal pigment epithelium by activating Nrf-2/HO-1 signaling pathway in early diabetic retinopathy.

AIMS: Diabetic retinopathy (DR) is a common complication of diabetes that causes visual impairment and blindness in adults. This study aimed to explore the protective effects of n-Butylidenephthalide (BP) on hyperglycemia-treated RPE in vitro and in vivo. MAIN METHODS: C57BL/6 mice were injected with STZ by intraperitoneal to induce early DR and orally administrated with 2 mg/kg BP every day for twelve weeks. Body weight and blood glucose were measured once a week. The level of retina damage was determined by TUNEL assay and H&E staining. The outer blood-retinal barrier integrity and RPE65 expression of retina were evaluated by immunofluorescence. In in vitro study, ARPE-19 cells were long-term cultured with high glucose and BP for 8 days and studied for cell survival, tight junction integrity, RPE65 expression, angiogenic factors, mitochondria membrane potential (MMP), and ROS by MTT assay, Western blot, ß-galactosidase staining, immunofluorescence, JC-1, or DCFH-DA. KEY FINDINGS: The results indicate that BP suppressed the hyperglycemic effect and maintained retina anatomy normalization, as well as protected RPE cell survival, tight junction integrity, and RPE65 expression in vitro and in vivo. In vitro results showed BP stimulated high glucose-treated ARPE-19 cell proliferation and suppressed senescence via ERK pathway. Numerous ROS production and MMP imbalance were prevented by BP through Nrf-2/HO-1 pathway. BP inhibited high glucose-induced RPE neovascularization by VEGF dysregulation. SIGNIFICANCE: BP significantly protected tight junction integrity and RPE cellular physiology through ERK/Nrf-2/HO-1 pathway to prevent DR progression. Thus, BP has great potential to be developed therapeutic agents or adjuvants for DR.

Patchouli alcohol induces G0 /G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage.

BACKGROUND: Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the leading causes of cancer-related deaths worldwide. Vincristine (VCR) is a chemotherapeutic agent for lung cancers; however, its effectiveness is limited by side effects and the development of drug resistance. Patchouli alcohol (PA), from Pogostemon cablin extract, is known to possess anti-inflammatory and anticancer properties. In this study, we investigated the role of PA in inducing reactive oxygen species (ROS)-mediated DNA damage in A549 and VCR-resistant A549/V16 NSCLC cells. METHODS: The anticancer potential of PA was studied using the MTT assay, colony formation, flow cytometry analysis, western blotting, DCFDA staining, immunofluorescence staining, and TUNEL assay techniques. RESULTS: The intracellular ROS levels were enhanced in PA-treated cells, activating the CHK1 and CHK2 signaling pathways. PA further inhibited proliferation and colony-forming abilities and induced cell cycle arrest at the G0 /G1 phase by regulating p53/p21 and CDK2/cyclin E1 expression. Moreover, PA increased the percentage of cells in the subG1 phase and induced apoptosis by activating the Bax/caspase-9/caspase-3 intrinsic pathway. In addition, drug resistance (p-glycoprotein) and cancer stem cell (CD44 and CD133) markers were downregulated after PA treatment. Furthermore, combining PA and cisplatin exhibited synergistic inhibitory activity in A549 and A549/V16 cells. CONCLUSIONS: PA induced ROS-mediated DNA damage, triggered cell cycle arrest and apoptosis, attenuated drug resistance and cancer stem cell phenotypes, and synergistically inhibited proliferation in combination with cisplatin. These findings suggest that PA has the potential to be used for the treatment of NSCLC with or without VCR resistance.

A lightweight network guided with differential matched filtering for retinal vessel segmentation.

The geometric morphology of retinal vessels reflects the state of cardiovascular health, and fundus images are important reference materials for ophthalmologists. Great progress has been made in automated vessel segmentation, but few studies have focused on thin vessel breakage and false-positives in areas with lesions or low contrast. In this work, we propose a new network, differential matched filtering guided attention UNet (DMF-AU), to address these issues, incorporating a differential matched filtering layer, feature anisotropic attention, and a multiscale consistency constrained backbone to perform thin vessel segmentation. The differential matched filtering is used for the early identification of locally linear vessels, and the resulting rough vessel map guides the backbone to learn vascular details. Feature anisotropic attention reinforces the vessel features of spatial linearity at each stage of the model. Multiscale constraints reduce the loss of vessel information while pooling within large receptive fields. In tests on multiple classical datasets, the proposed model performed well compared with other algorithms on several specially designed criteria for vessel segmentation. DMF-AU is a high-performance, lightweight vessel segmentation model. The source code is at https://github.com/tyb311/DMF-AU.

The effects of patchouli alcohol and combination with cisplatin on proliferation, apoptosis and migration in B16F10 melanoma cells.

Melanoma is a highly metastatic cancer with a low incidence rate, but a high mortality rate. Patchouli alcohol (PA), a tricyclic sesquiterpene, is considered the main active component in Pogostemon cablin Benth, which improves wound healing and has anti-tumorigenic activity. However, the pharmacological action of PA on anti-melanoma remains unclear. Thus, the present study aimed to investigate the role of PA in the proliferation, cell cycle, apoptosis and migration of melanoma cells. These results indicated that PA selectively inhibited the proliferation of B16F10 cells in a dose- and time-dependent manner. It induced cell cycle arrest at the G0 /G1 phase and typical morphological changes in apoptosis, such as chromatin condensation, DNA fragmentation and apoptotic bodies. In addition, PA reduced the migratory ability of B16F10 cells by upregulating E-cadherin and downregulating p-Smad2/3, vimentin, MMP-2 and MMP-9 expression. PA was also found to strongly suppress tumour growth in vivo. Furthermore, PA combined with cisplatin synergistically inhibited colony formation and migration of B16F10 cells and attenuated the development of resistance to treatment. Therefore, the results of this study indicate that PA may play a pivotal role in inducing apoptosis and reducing the migration of melanoma cells, and may thus be a potential candidate for melanoma treatment.