Prognostic Significance of VAV3 Gene Variants and Expression in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is characterized by high mortality and morbidity rates. Vav guanine nucleotide exchange factors (VAVs), crucial for signal transduction between cell membrane receptors and intracellular mediators, have been implicated in carcinogenesis. However, their potential prognostic value in RCC remains unclear. The impact of 150 common VAV polymorphisms on RCC risk and survival was investigated in a cohort of 630 individuals. Publicly available gene expression datasets were utilized to analyze VAV gene expression in relation to patient outcomes. The VAV3 rs17019888 polymorphism was significantly associated with RCC risk and overall survival after adjusting for false discovery rates. Expression quantitative trait loci analysis revealed that the risk allele of rs17019888 is linked to reduced VAV3 expression. Analysis of 19 kidney cancer gene expression datasets revealed lower VAV3 expression in RCC tissues compared to normal tissues, with higher expression correlating with better prognosis. Gene set enrichment analysis demonstrated that VAV3 negatively regulates the ubiquitin-proteasome system, extracellular matrix and membrane receptors, inflammatory responses, matrix metalloproteinases, and cell cycle pathways. Furthermore, elevated VAV3 expression was associated with increased infiltration of B cells, macrophages, and neutrophils into the RCC tumor microenvironment. Our findings suggest that VAV3 gene variants influence RCC risk and survival, contributing to a favorable prognosis in RCC.

Crosstalk between Myopia and Inflammation: A Mini Review.

Myopia represents a significant public health concern worldwide, particularly affecting the ocular health of children and adolescents. The escalating prevalence of myopia in recent years underscores its urgency as a health issue among this demographic. Research indicates a profound connection between the onset of myopia, inflammatory processes and fibrosis. Individuals with inflammatory conditions like allergic conjunctivitis, choroiditis, systemic lupus erythematosus, and diabetes exhibit a heightened susceptibility to myopia. Conversely, myopic patients are at an increased risk of developing ocular inflammatory disorders, notably idiopathic multifocal choroiditis. We postulate that the expression of inflammatory markers, including NF-κB, TGF-ß, IL-1ß, IL-6, IL-8, and TNF-α, may contribute to the chronic inflammatory state observed in myopia. This paper highlights a substantial correlation between myopia and inflammation, suggesting the potential efficacy of anti-inflammatory agents in managing inflammation and slowing myopia progression.

Comparative analysis of genetic risk scores for predicting biochemical recurrence in prostate cancer patients after radical prostatectomy.

BACKGROUND: In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on phenotypes. To solve the above problems, methods that can use variants with low genetic effects, such as genetic risk score (GRS), have been developed to predict disease risk. METHODS: As the GRS model with the most incredible prediction power for complex diseases has not been determined, our study used simulation data and prostate cancer data to explore the disease prediction power of three GRS models, including the simple count genetic risk score (SC-GRS), the direct logistic regression genetic risk score (DL-GRS), and the explained variance weighted GRS based on directed logistic regression (EVDL-GRS). RESULTS AND CONCLUSIONS: We used 26 SNPs to establish GRS models to predict the risk of biochemical recurrence (BCR) after radical prostatectomy. Combining clinical variables such as age at diagnosis, body mass index, prostate-specific antigen, Gleason score, pathologic T stage, and surgical margin and GRS models has better predictive power for BCR. The results of simulation data (statistical power = 0.707) and prostate cancer data (area under curve = 0.8462) show that DL-GRS has the best prediction performance. The rs455192 was the most relevant locus for BCR (p = 2.496 × 10-6) in our study.

Deep-learning enabled smart insole system aiming for multifunctional foot-healthcare applications.

Real-time foot pressure monitoring using wearable smart systems, with comprehensive foot health monitoring and analysis, can enhance quality of life and prevent foot-related diseases. However, traditional smart insole solutions that rely on basic data analysis methods of manual feature extraction are limited to real-time plantar pressure mapping and gait analysis, failing to meet the diverse needs of users for comprehensive foot healthcare. To address this, we propose a deep learning-enabled smart insole system comprising a plantar pressure sensing insole, portable circuit board, deep learning and data analysis blocks, and software interface. The capacitive sensing insole can map both static and dynamic plantar pressure with a wide range over 500 kPa and excellent sensitivity. Statistical tools are used to analyze long-term foot pressure usage data, providing indicators for early prevention of foot diseases and key data labels for deep learning algorithms to uncover insights into the relationship between plantar pressure patterns and foot issues. Additionally, a segmentation method assisted deep learning model is implemented for exercise-fatigue recognition as a proof of concept, achieving a high classification accuracy of 95%. The system also demonstrates various foot healthcare applications, including daily activity statistics, exercise injury avoidance, and diabetic foot ulcer prevention.

miR-92b-3p protects retinal tissues against DNA damage and apoptosis by targeting BTG2 in experimental myopia.

BACKGROUND: Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2. METHODS: Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting. RESULTS: Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia. CONCLUSION: In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.

Data-driven evaluation of electric vehicle energy consumption for generalizing standard testing to real-world driving.

Standard energy-consumption testing, providing the only publicly available quantifiable measure of battery electric vehicle (BEV) energy consumption, is crucial for promoting transparency and accountability in the electrified automotive industry; however, significant discrepancies between standard testing and real-world driving have hindered energy and environmental assessments of BEVs and their broader adoption. In this study, we propose a data-driven evaluation method for standard testing to characterize BEV energy consumption. By decoupling the impact of the driving profile, our evaluation approach is generalizable to various driving conditions. In experiments with our approach for estimating energy consumption, we achieve a 3.84% estimation error for 13 different multiregional standardized test cycles and a 7.12% estimation error for 106 diverse real-world trips. Our results highlight the great potential of the proposed approach for promoting public awareness of BEV energy consumption through standard testing while also providing a reliable fundamental model of BEVs.

Diagnostic accuracy of contrast-enhanced CT versus PET/CT for advanced ovarian cancer staging: a comparative systematic review and meta-analysis.

PURPOSE: Accurate staging of ovarian cancer is critical to guide optimal management pathways. North American guidelines recommend contrast-enhanced CT as the primary work-up for staging ovarian cancer. This meta-analysis aims to compare the diagnostic accuracy of contrast-enhanced CT alone to PET/CT for detecting abdominal metastases in patients with a new or suspected diagnosis of ovarian cancer. MATERIALS AND METHODS: A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the gray literature from inception to October 2022 was performed. Studies with a minimum of 5 patients evaluating the diagnostic accuracy of contrast-enhanced CT and/or PET/CT for detecting stage 3 ovarian cancer as defined by a surgical/histopathological reference standard ± clinical follow-up were included. Study, clinical, imaging, and accuracy data for eligible studies were independently acquired by two reviewers. Primary meta-analysis was performed in studies reporting accuracy on a per-patient basis using a bivariate mixed-effects regression model. Risk of bias was evaluated using QUADAS-2. RESULTS: From 3701 citations, 15 studies (918 patients with mean age ranging from 51 to 65 years) were included in the systematic review. Twelve studies evaluated contrast-enhanced CT (6 using a per-patient assessment and 6 using a per-region assessment) and 11 studies evaluated PET/CT (7 using a per-patient assessment and 4 using a per-region assessment). All but one reporting study used consensus reading. Respective sensitivity and specificity values on a per-patient basis were 82% (67-91%, 95% CI) and 72% (59-82%) for contrast-enhanced CT and 87% (75-94%) and 90% (82-95%) for PET/CT. There was no significant difference in sensitivities between modalities (p = 0.29), but PET/CT was significantly more specific than CT (p < 0.01). Presumed variability could not be assessed in any single category due to limited studies using per-patient assessment. Studies were almost entirely low risk for bias and applicability concerns using QUADAS-2. CONCLUSION: Contrast-enhanced CT demonstrates non-inferior sensitivity compared to PET/CT, although PET/CT may still serve as an alternative and/or supplement to CT alone prior to and/or in lieu of diagnostic laparoscopy in patients with ovarian cancer. Future revisions to existing guidelines should consider these results to further refine the individualized pretherapeutic diagnostic pathway.

Identifying the role of MTHFD1L in prostate cancer progression from genetic analysis and experimental validation.

One-carbon metabolism plays a crucial role in tumorigenesis as it supplies the one-carbon units necessary for nucleotide synthesis, epigenetic regulation, and redox metabolism, ensuring the rapid proliferation of cancer cells. However, their roles in prostate cancer progression remain poorly understood. In this study, we investigated the association between genetic variants in the one-carbon metabolism pathway and clinical outcomes in patients receiving androgen deprivation therapy for prostate cancer. The associations of 130 single-nucleotide polymorphisms located within 14 genes involved in the one-carbon metabolism pathway with cancer-specific survival (CSS), overall survival, and progression-free survival were assessed using Cox regression in 630 patients with prostate cancer. Subsequently, functional studies were performed using prostate cancer cell lines. After adjusting for covariates and multiple testing, MTHFD1L rs2073190 was found to be significantly associated with CSS (P = 0.000184). Further pooled analysis of multiple datasets demonstrated that MTHFD1L was upregulated in prostate cancer and increased MTHFD1L expression was positively correlated with tumor aggressiveness and poor patient prognosis. Functionally, MTHFD1L knockdown suppressed prostate cancer cell proliferation and colony formation. RNA sequencing and pathway analysis revealed that differentially expressed genes were predominantly enriched in the cell cycle pathway. In conclusion, genetic variants in MTHFD1L of one-carbon metabolism may serve as promising predictors, and our findings offer valuable insights into the underlying genetic mechanisms of prostate cancer progression.

Integrated analysis identifies GABRB3 as a biomarker in prostate cancer.

BACKGROUND: Treatment failure following androgen deprivation therapy (ADT) presents a significant challenge in the management of advanced prostate cancer. Thus, understanding the genetic factors influencing this process could facilitate the development of personalized treatments and innovative therapeutic strategies. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in controlling cell growth and tumorigenesis. We hypothesized that genetic variants within this pathway may affect the clinical outcomes of patients undergoing ADT for prostate cancer. METHODS: We genotyped 399 single-nucleotide polymorphisms (SNPs) across 28 core PI3K/AKT pathway genes in a cohort of 630 patients with prostate cancer undergoing ADT. We assessed the potential association of the SNPs with patient survival. Functional analyses of the implicated genes were also performed to evaluate their effects on prostate cancer. RESULTS: After multivariate Cox regression analysis and multiple testing correction, GABRB3 rs12591845 exhibited the most significant association with both overall and cancer-specific survivals (P < 0.003). A comprehensive pooled analysis of 16 independent gene expression datasets revealed elevated expression of GABRB3 in prostate cancer tissues compared to that in normal tissues (P < 0.001). Furthermore, gene set enrichment analysis unveiled differential enrichment of pathways such as myogenesis, interferon γ and α responses, and the MYC proto-oncogene pathway in tumors with elevated GABRB3 expression, implying a role for GABRB3 in prostate cancer. CONCLUSION: Our results suggest that rs12591845 could potentially serve as a valuable prognostic indicator for patients undergoing ADT. The potential role of GABRB3 in promoting prostate tumorigenesis is also highlighted.

Impact of Size Thresholds on the Diagnosis of Incidental Adrenal Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: Preferred size-threshold recommendations for management of incidental adrenal lesions remain controversial. PURPOSE: This meta-analysis aimed to compare the diagnostic accuracy of different size thresholds for detecting malignancy in patients with incidental adrenal lesions on imaging. MATERIALS AND METHODS: A systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature, covering the period from inception to September 2021, was performed. Studies with >10 patients evaluating the diagnostic accuracy of imaging size thresholds for detecting malignancy in patients with incidental adrenal lesions and no prior history of cancer were included. Study, clinical, imaging, and accuracy data for eligible studies were independently acquired by two reviewers. Primary meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: From 2,690 citations, 40 studies (9,794 patients with mean age ranging from 41 to 66 years) were included. Most (36 of 40) were retrospective single-center studies. CT with or without MRI served as the index test(s). Sensitivity and specificity values, respectively, by size threshold used in the included studies were as follows: 85% (95% confidence interval [CI] 74%-91%) and 39% (95% CI 23%-57%) for 3-cm thresholds; 85% (95% CI 78%-90%) and 75% (95% CI 62%-85%) for 4-cm thresholds; 70% (95% CI 56%-81%) and 74% (95% CI 59%-85%) for 5-cm thresholds; and 75% (95% CI 67%-82%) and 77% (95% CI 62%-87%) for 6-cm thresholds. No cause for variability in sensitivity or specificity was identified on subgroup analysis of the 4-cm threshold. Nearly half of the studies (19 of 40) had at least one QUADAS-2 domain with a high risk of bias. CONCLUSIONS: A 4-cm size threshold demonstrates the highest combined sensitivity and specificity, with a preserved specificity compared with higher size thresholds, but with a trend toward improved sensitivity. Future research reevaluating 4-5 cm size thresholds while excluding characteristically benign lesions by imaging may help redefine a size threshold that has improved specificity but preserved sensitivity, compared with the existing 4-cm threshold.

Comparison of Endophthalmitis Rates after Alcohol-Based Chlorhexidine and Povidone-Iodine Antisepsis for Intravitreal Injections.

OBJECTIVE: Intravitreal injections (IVIs) are the most frequently performed intraocular procedure in Canada. Povidone-iodine (PI) is the current gold standard for antisepsis for IVI and is widely used; chlorhexidine (CH) is a possible alternative antiseptic agent. This study aims to compare rates of endophthalmitis after IVI with 0.05% chlorhexidine with a 4% alcohol base antisepsis to rates of endophthalmitis after IVI with 10% PI antisepsis. DESIGN: Retrospective cohort study. SUBJECTS: Eyes that received IVI between May 2019 and October 2022 at a group retina practice in Edmonton, Canada. METHODS: Eyes at a single center received focal conjunctival application of either 10% PI antisepsis or 0.05% CH in 4% alcohol antisepsis for 30 seconds before each IVI. MAIN OUTCOME MEASURE: Rates of endophthalmitis between the PI and CH groups. RESULTS: A total of 170 952 IVIs were performed during the study period. A total of 31 135 were performed using CH prophylaxis compared with 139 817 with PI prophylaxis. Among all IVIs there were 49 total cases of endophthalmitis, 29 in the PI group (0.021%) and 20 in the CH group (0.064%). There was a statistically significant difference in the rates of endophthalmitis between the 2 groups (P < 0.001). The odds ratio for developing endophthalmitis with CH antisepsis was 3.1 (95% confidence interval, 1.9-5.2) compared with PI antisepsis. There were increased odds of developing endophthalmitis with aflibercept injection compared with bevacizumab (odds ratio, 3.48; 95% confidence interval, 2.09-7.24). CONCLUSIONS: There is a statistically significant difference in rates of endophthalmitis between alcohol-based CH and PI antisepsis for IVI in our patient population utilizing the methods discussed. In our center, alcohol-based CH is now considered a second-line antiseptic agent. Further studies are warranted to further assess the endophthalmitis rate utilizing these 2 antiseptic agents. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Adrenal Mass Biopsy in Patients Without Extraadrenal Primary Malignancy: A Multicenter Study.

BACKGROUND. Adrenal washout CT is not useful for evaluating incidental adrenal masses in patients without known or suspected primary extraadrenal malignancy. OBJECTIVE. The purpose of our study was to evaluate the diagnostic utility of adrenal mass biopsy in patients without known or suspected extraadrenal primary malignancy. METHODS. This retrospective six-center study included 69 patients (mean age, 56 years; 32 men, 37 women) without known or suspected extraadrenal primary malignancy who underwent image-guided core needle biopsy between January 2004 and June 2021 of a mass suspected to be arising from the adrenal gland. Biopsy results were classified as diagnostic or nondiagnostic. For masses resected after biopsy, histopathologic concordance was assessed between diagnoses from biopsy and resection. Masses were classified as benign or malignant by resection or imaging follow-up, and all nondi-agnostic biopsies were classified as false results. RESULTS. The median mass size was 7.4 cm (range, 1.9-19.2 cm). Adrenal mass biopsy had a diagnostic yield of 64% (44/69; 95% CI, 51-75%). After biopsy, 25 masses were resected, and 44 had imaging follow-up. Of the masses that were resected after diagnostic biopsy, diagnosis was concordant between biopsy and resection in 100% (12/12). Of the 13 masses that were resected after nondiagnostic biopsy, the diagnosis from re-section was benign in eight masses and malignant in five masses. The 44 masses with imaging follow-up included one mass with diagnostic biopsy yielding benign adenoma and two masses with nondiagnostic biopsy results that were classified as malignant by imaging follow-up. Biopsy had overall sensitivity and specificity for malignancy of 73% (22/30) and 54% (21/39), respectively; diagnostic biopsies had sensitivity and specificity for malignancy of 96% (22/23) and 100% (21/21), respectively. Among nine nondi-agnostic biopsies reported as adrenocortical neoplasm, six were classified as malignant by the reference standard (resection showing adrenocortical carcinoma in four, resection showing adrenocortical neoplasm of uncertain malignant potential in one, imaging follow-up consistent with malignancy in one). CONCLUSION. Adrenal mass biopsy had low diagnostic yield, with low sensitivity and low specificity for malignancy. A biopsy result of adrenocortical neoplasm did not reliably differentiate benign and malignant adrenal masses. CLINICAL IMPACT. Biopsy appears to have limited utility for the evaluation of incidental adrenal masses in patients without primary extraadrenal malignancy.

Spontaneous Imbibition in Nanomatrix-Fracture of Low Permeability Using Multiscale Nanofluidic Chips.

Spontaneous imbibition has garnered increasing attention as an attractive mechanism for developing tight reservoirs. Despite valuable insights from previous experiments, there remains a lack of understanding regarding the imbibition process within multiscale nanopore-fracture networks. In this work, we devised an innovative multiscale model incorporating over 105 nanochannels and integrating a microfracture network to explore the complex imbibition behavior in tight formations. Additionally, fracture-free nanomatrix models with low permeability were developed for comparative discussions. The results show that the Lucas-Washburn equation remains valid at the tremendous fracture-free nanopore networks under the confinement of 500 nm, with a relative deviation of ±6%. The nanomatrix's heterogeneity hinders the imbibition rate, resulting in a reduction of 4.6 to 10.8% in the imbibition slope. The viscosity plays a dominant role in the change of imbibition slope as temperature varies. Our experiments also found that the interactions between the nanomatrix and bulk fracture complicate the imbibition process. A single wetting front no longer applies in the nanomatrix-fracture networks. Differing fracture/microchannel connectivity leads to disparities in macroscopic patterns, saturation rates, and flow directions. The spatial arrangement of fractures significantly impacts the imbibition time. Overall, this work based on nanofluidic techniques systematically explores the effects of matrix heterogeneity, temperature, and fractures on the imbibition process. The real-time in situ visualization of fluid distribution in multiscale matrix-fracture systems has been achieved, which offers theoretical guidance for practical engineering applications.

Electroacupuncture alleviates ciliary muscle cell apoptosis in lens-induced myopic guinea pigs through inhibiting the mitochondrial signaling pathway.

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

Suppressive effect of nitric oxide synthase (NOS) inhibitor L-NMMA acetate on choroidal fibrosis in experimental myopic guinea pigs through the nitric oxide signaling pathway.

Myopia is one of the most prevalent eye diseases that seriously threaten the eyesight of children and adolescents worldwide. However, the pathogenesis is still unclear, and effective drugs are still scarce. In the present study, the guinea pigs were randomly divided into a normal control (NC) group, a lens-induced myopia (LIM) group, a NOS inhibitor (L-NMMA) injection group, and a NOS inhibitor solvent phosphate-buffered saline (PBS) group and the animals received relevant treatments. After 2- and 4-week different treatments, we noted that the refraction and choroidal thickness in the LIM group decreased compared with the NC group, whereas the ocular axial length increased significantly, and the choroid showed a fibrotic trend. The expression of NOS1, NOS3, TGF-ß1, COLI, and α-SMA at gene and protein levels was increased significantly in the choroid (all P < 0.05). After intravitreal injection of NOS inhibitor L-NMMA, we found that compared with the LIM group, the refraction and the choroidal thickness significantly increased, whereas the axial length reduced significantly, accompanied by an increase of choroidal thickness and an improvement of choroidal fibrosis. The expression levels of choroidal NOS1, NOS3, TGF-ß, COLI, and α-SMA were significantly reduced (all P < 0.05). In conclusion, the trend of choroidal fibrosis in LIM guinea pigs is positively correlated with the increase in axial length. The NOS inhibitor L-NMMA can alleviate the process of choroidal fibrosis in myopic guinea pigs by inhibiting NO signaling pathway.

Cystic retroperitoneal dedifferentiated liposarcoma: A case report.

Liposarcoma is the most common primary retroperitoneal sarcoma in adults. We report the case of an 86-year-old male who presented to the emergency department with frequent falls and unexplained weight loss that was found to have a cystic retroperitoneal dedifferentiated liposarcoma. Initial computed tomography revealed a large heterogeneous complex cystic hypoenhancing lesion in the left retroperitoneum. Subsequent magnetic resonance imaging demonstrates a multilocular cystic mass with microscopic lipid content, diffusion restriction, and enhancing nodular soft-tissue components. Histologic examination of the tissue sample following biopsy is consistent with cystic retroperitoneal dedifferentiated liposarcoma. Further management was not pursued due to the patient's advanced age and frailty.

CYBA as a Potential Biomarker for Renal Cell Carcinoma: Evidence from an Integrated Genetic Analysis.

BACKGROUND/AIM: Oxidative stress plays an important role in various pathogenic processes, and disruption in the coordinated production of NADPH oxidase (NOX)-derived reactive oxygen species has been associated with carcinogenesis. However, little is known about whether genetic variants in NOX can contribute to the development of renal cell carcinoma (RCC). PATIENTS AND METHODS: This study aimed to bridge this knowledge gap by analysing the association of 10 single-nucleotide polymorphisms in the phagocyte NOX genes, CYBA and CYBB, with RCC risk and tumour characteristics in 630 RCC patients and controls. Differential gene expression and patient prognosis analyses were performed using gene expression data obtained from public databases. RESULTS: Multivariate analysis and multiple testing corrections revealed the A allele of rs7195830 in CYBA to be a significant risk allele for RCC, compared to the G allele [odds ratio (OR)=1.70, 95% confidence interval (CI)=1.27-2.26, p<0.001]. A pooled analysis of 17 renal cancer gene expression datasets revealed a higher CYBA expression in RCC than in normal tissues. Moreover, high CYBA expression was associated with advanced tumour characteristics and worse patient prognosis. CONCLUSION: CYBA might play an oncogenic role in RCC and serve as a predictive indicator of patient prognosis.

Elevated retinal fibrosis in experimental myopia is involved in the activation of the PI3K/AKT/ERK signaling pathway.

OBJECTIVE: This study aimed to investigate the regulatory role of the PI3K/AKT/ERK signaling pathway in retinal fibrosis in -6.0 diopter (D) lens-induced myopic (LIM) guinea pigs. METHODS: Biological measurements of eye tissues were performed on guinea pigs to obtain their refraction, axial length, retinal thickness, physiological function, and fundus retinal status. In addition, Masson staining and immunohistochemical (IHC) assay were further done to explore the changes in retinal morphology after myopic induction. Meanwhile, hydroxyproline (HYP) content was measured to evaluate the degree of retinal fibrosis. Moreover, the levels of the PI3K/AKT/ERK signaling pathway and fibrosis-related molecules in retinal tissues including matrix metalloproteinase 2(MMP2), collagen type I (Collagen I), and α-smooth muscle actin (α-SMA) were detected by real-time quantitative PCR (qPCR) and Western blot. RESULTS: The LIM guinea pigs showed a significant myopic shift in refractive error and an increase in axial length compared with those of the normal control (NC) group. Masson staining, hydroxyproline content determination, and IHC showed an increase in retinal fibrosis. After myopic induction, qPCR and western blot analyses showed that phosphatidylinositol-3-kinase catalytic subunit α (PIK3CA), protein kinase B (AKT), extracellular regulated protein kinase 1/2 (ERK1/2), MMP2, Collagen I, and α-SMA were consistently elevated in the LIM group than those in the NC group. CONCLUSION: The PI3K/AKT/ERK signaling pathway was activated in the retinal tissues of myopic guinea pigs, which exaggerated fibrotic lesions and reduced retinal thickness, ultimately leading to retinal physiological dysfunctions in myopic guinea pigs.

Epithelial polarization in the 3D matrix requires MST3 signaling to regulate ZO-1 position.

Apical-basal cell polarity must be tightly controlled for epithelial cyst and tubule formation, and these are important functional units in various epithelial organs. Polarization is achieved through the coordination of several molecules that divide cells into an apical domain and a basolateral domain, which are separated from tight and adherens junctions. Cdc42 regulates cytoskeletal organization and the tight junction protein ZO-1 at the apical margin of epithelial cell junctions. MST kinases control organ size through the regulation of cell proliferation and cell polarity. For example, MST1 relays the Rap1 signal to induce cell polarity and adhesion of lymphocytes. Our previous study showed that MST3 was involved in E-cadherin regulation and migration in MCF7 cells. In vivo, MST3 knockout mice exhibited higher ENaC expression at the apical site of renal tubules, resulting in hypertension. However, it was not clear whether MST3 was involved in cell polarity. Here, control MDCK cells, HA-MST3 and HA-MST3 kinase-dead (HA-MST3-KD) overexpressing MDCK cells were cultured in collagen or Matrigel. We found that the cysts of HA-MST3 cells were fewer and smaller than those of control MDCK cells; ZO-1 was delayed to the apical site of cysts and in cell-cell contact in the Ca2+ switch assay. However, HA-MST3-KD cells exhibited multilumen cysts. Intensive F-actin stress fibers were observed in HA-MST3 cells with higher Cdc42 activity; in contrast, HA-MST3-KD cells had lower Cdc42 activity and weaker F-actin staining. In this study, we identified a new MST3 function in the establishment of cell polarity through Cdc42 regulation.

Anticancer Effects of Morusin in Prostate Cancer via Inhibition of Akt/mTOR Signaling Pathway.

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. The majority of PCa incidences eventually progress to castration-resistant PCa (CRPC), thereby establishing an urgent need for new effective therapeutic strategies. This study aims to examine the effects of morusin, a prenylated flavonoid isolated from Morus alba L., on PCa progression and identify the regulatory mechanism of morusin. Cell growth, cell migration and invasion, and the expression of EMT markers were examined. Cycle progression and cell apoptosis were examined using flow cytometry and a TUNEL assay, while transcriptome analysis was performed using RNA-seq with results being further validated using real-time PCR and western blot. A xenograft PCa model was used to examine tumor growth. Our experimental results indicated that morusin significantly attenuated the growth of PC-3 and 22Rv1 human PCa cells; moreover, morusin significantly suppressed TGF-[Formula: see text]-induced cell migration and invasion and inhibited EMT in PC-3 and 22Rv1 cells. Significantly, morusin treatment caused cell cycle arrest at the G2/M phase and induced cell apoptosis in PC-3 and 22Rv1 cells. Morusin also attenuated tumor growth in a xenograft murine model. The results of RNA-seq indicated that morusin regulated PCa cells through the Akt/mTOR signaling pathway, while our western blot results confirmed that morusin suppressed phosphorylation of AKT, mTOR, p70S6K, and downregulation of the expression of Raptor and Rictor in vitro and in vivo. These results suggest that morusin has antitumor activities on regulating PCa progression, including migration, invasion, and formation of metastasis, and might be a potential drug for CRPC treatment.