The JMJD family of histone demethylase and their intimate links to cardiovascular disease.

The incidence rate and mortality rate of cardiovascular disease rank first in the world. It is associated with various high-risk factors, and there is no single cause. Epigenetic modifications, such as DNA methylation or histone modification, actively participate in the initiation and development of cardiovascular diseases. Histone lysine methylation is a type of histone post-translational modification. The human Jumonji C domain (JMJD) protein family consists of more than 30 members. JMJD proteins participate in many key nuclear processes and play a key role in the specific regulation of gene expression, DNA damage and repair, and DNA replication. Importantly, increasing evidence shows that JMJD proteins are abnormally expressed in cardiovascular diseases, which may be a potential mechanism for the occurrence and development of these diseases. Here, we discuss the key roles of JMJD proteins in various common cardiovascular diseases. This includes histone lysine demethylase, which has been studied in depth, and less-studied JMJD members. Furthermore, we focus on the epigenetic changes induced by each JMJD member, summarize recent research progress, and evaluate their relationship with cardiovascular diseases and therapeutic potential.

RNA-binding proteins in breast cancer: Biological implications and therapeutic opportunities.

RNA-binding proteins (RBPs) refer to a class of proteins that participate in alternative splicing, RNA stability, polyadenylation, localization and translation of RNAs, thus regulating gene expression in post-transcriptional manner. Dysregulation of RNA-RBP interaction contributes to various diseases, including cancer. In breast cancer, disorders in RBP expression and function influence the biological characteristics of tumor cells. Targeting RBPs has fostered the development of innovative therapies for breast cancer. However, the RBP-related mechanisms in breast cancer are not completely clear. In this review, we summarize the regulatory mechanisms of RBPs and their signaling crosstalk in breast cancer. Specifically, we emphasize the potential of certain RBPs as prognostic factors due to their effects on proliferation, invasion, apoptosis, and therapy resistance of breast cancer cells. Most importantly, we present a comprehensive overview of the latest RBP-related therapeutic strategies and novel therapeutic targets that have proven to be useful in the treatment of breast cancer.

Effects of different Ficus feeding experiences on host preference of Perina nuda larvae (Lepidoptera: Lymantriidae).

Perina nuda (Lepidoptera: Lymantriidae) is a serious pest of banyan trees (Ficus spp.), which is distributed in South China, but little is known about the host preference on the different banyan tree species. To address this gap, we conducted experiments to investigate larval feeding preferences, assessing the impact of feeding experience in both choice and no-choice conditions. Fifth and sixth instars were exposed to 4 banyan species, and food intake, feeding area, and relative ingestion index were measured. Our findings reveal that Ficus concinna was the preferred host of fifth instars in choice tests, while sixth instars exhibited a preference for this host in no-choice tests. In contrast, fifth instars did not display a significant preference for any of the 4 species in no-choice tests. However, sixth instars fed on F. microcarpa, F. altissima, and F. concinna continued to exhibit a preference for the original host. These observations indicate that larval feeding preference changes with instar, and feeding experience contributes to a preference for the original host. Consequently, the feeding preference of P. nuda larvae is influenced by multiple factors, including instar and previous feeding experience. These findings enhance our understanding of P. nuda's ecological interactions and its potential impact on various banyan tree species.

HER2-targeting two-dimensional black phosphorus as a nanoplatform for chemo-photothermal therapy in breast cancer.

Trastuzumab (Tmab) targeted therapy or its combination with chemotherapy is normally insufficient to elicit a comprehensive therapeutic response owing to the inherent or acquired drug resistance and systemic toxicity observed in highly invasive HER2-positive breast cancer. In this study, we propose a novel approach that integrates photothermal therapy (PTT) with targeted therapy and chemotherapy, thereby achieving additive or synergistic therapeutic outcomes. We utilize PEGylated two-dimensional black phosphorus (2D BP) as a nanoplatform and photothermal agent to load chemotherapeutic drug mitoxantrone (MTO) and conjugate with Tmab (BP-PEG-MTO-Tmab). The in vitro and in vivo experiments demonstrated that the HER2-targeting BP-PEG-MTO-Tmab complexes exhibited desirable biocompatibility, safety and enhanced cancer cell uptake efficiency, resulting in increased accumulation and prolonged retention of BP and MTO within tumors. Consequently, the complex improved photothermal and chemotherapy treatment efficacy in HER2-positive cells in vitro and a subcutaneous tumor model in vivo, while minimized harm to normal cells and showed desirable organ compatibility. Collectively, our study provides compelling evidence for the remarkable efficacy of targeted and synergistic chemo-photothermal therapy utilizing all-in-one nanoparticles as a delivery system for BP and chemotherapeutic drug in HER2-positive breast cancer.

Prevalence and factors of COVID-19 vaccine refusal among solid cancer patients in China: an application of the health belief model.

Introduction: It is essential to protect cancer patients from contracting COVID-19 through vaccination. A majority of cancer patients are recommended by international health authorities to take up the vaccines. COVID-19 vaccine refusal among cancer patients during the pandemic period is under-researched. This study investigated factors of vaccine refusal based on the Health Belief Model (HBM). Methods: A cross-sectional study was conducted among female breast cancer patients, male/female thyroid cancer patients, and gynecological cancer patients in Shantou, China from April to August 2022 (n = 1,115). Multinomial logistic regression analysis adjusted for socio-demographics was conducted to test factors of COVID-19. Adjusted odds ratios of the two models comparing vaccine refusal vs. "vaccine non-refusal" and vaccine refusal vs. ever-vaccination were derived and presented. Results: Of all the participants, the prevalence of vaccine refusal, "vaccine non-refusal," and ever-vaccination was 25.9, 22.2, and 51.8%, respectively. In both multinomial logistic regression models, significant factors of vaccine refusal included socio-demographics (age, education level, employment status, monthly household income, cancer type, duration since cancer diagnosis, current treatment status) and some vaccine-related HBM (perceived benefits, perceived barriers, cue to action, and self-efficacy). Perceived severity of COVID-19 was significant only in the vaccine refusal vs. ever-vaccination model. In neither model, perceived susceptibility to contract COVID-19 was statistically significant. Conclusion: About » of the participants expressed vaccine refusal. Interventions are warranted. Future longitudinal studies are needed to verify this study's findings. Pilot interventions should also be launched to test effectiveness of interventions modifying the significant HBM factors found in this study.

Online short videos promoting public breast cancer literacy: a pretest-posttest control group trial on efficiency, attitude, and influencing factors.

Background: Short videos on social media are playing an increasingly important role in cancer health education today. It is important to explore how the actual communication effect of health videos and the knowledge absorption of users are influenced by different factors of the video creation process. Objective: The objective of our study is to access the factors influencing breast cancer health education through short videos on efficiency and quality. Methods: Three pairs of videos about breast health were created and participants completed questionnaires before and after watching the videos. A paired t-test was used to analyze within-group change scores. RM-ANOVA was used to assess the relationship between the pretest, posttest, and three variables. Results: Watching short videos can significantly increase viewers' knowledge of related health topics (p < 0.05). The viewers' concentration level while watching was significantly higher for the video with background music (BGM) than for the video without BGM (p = 0.006). The viewers' willingness to share was significantly higher for the video with a progress bar than for the video without a progress bar (p = 0.02). Using an interpreter wearing a doctor's uniform instead of casual wear and setting a progress bar can significantly improve the efficiency of knowledge absorption (p < 0.05). Conclusion: A uniformed interpreter, BGM and a progress bar are factors influencing the efficiency of short health videos. They can be applied in video making to explore better ways of promoting cancer health education in the new mobile Internet environment.

CD146 interaction with integrin ß1 activates LATS1-YAP signaling and induces radiation-resistance in breast cancer cells.

Radiotherapy is an indispensable modality in comprehensive treatment of breast cancer. However, inherent or acquired radiation resistance of tumors compromises the efficacy of radiotherapy. Herein, we found that CD146, a unique epithelial-to-mesenchymal transition (EMT) inducer particularly highly expressed in triple-negative breast cancer (TNBC), is dramatically induced by ionizing irradiation. Further study demonstrates that CD146 promotes tumor cell radioresistance in vitro and in vivo. Specifically, we report the underlying mechanism that CD146 activates YAP protein, and drives its relocation from plasma to nucleus by regulating LATS1, and promoting abnormal DNA damage repair, as well as inducing EMT and stemness. Moreover, CD146 can form a novel co-receptor complex with integrin ß1 and induces radiation-resistance in breast cancer. Dual inhibition of CD146 and integrin ß1 activity had a stronger inhibitory effect on breast cancer tumor growth and synergistically increased their sensitivity to radiotherapy. This study identifies a unique function of CD146 implicates with integrin ß1 and YAP signaling, contributing to radiation resistance. Targeted therapy against CD146 or inhibition of integrin ß1 is a potential strategy to overcome radiotherapeutic resistance of breast cancer.

CD146 increases stemness and aggressiveness in glioblastoma and activates YAP signaling.

Glioblastoma (GBM), a highly malignant and lethal brain tumor, is characterized by diffuse invasion into the brain and chemo-radiotherapy resistance resulting in poor prognosis. In this study, we examined the involvement of the cell adhesion molecule CD146/MCAM in regulating GBM aggressiveness. Analyses of GBM transcript expression databases revealed correlations of elevated CD146 levels with higher glioma grades, IDH-wildtype and unmethylated MGMT phenotypes, poor response to chemo-radiotherapy and worse overall survival. In a panel of GBM stem cells (GSCs) variable expression levels of CD146 were detected, which strongly increased upon adherent growth. CD146 was linked with mesenchymal transition since expression increased in TGF-ß-treated U-87MG cells. Ectopic overexpression of CD146/GFP in GG16 cells enhanced the mesenchymal phenotype and resulted in increased cell invasion. Conversely, GSC23-CD146 knockouts had decreased mesenchymal marker expression and reduced cell invasion in transwell and GBM-cortical assembloid assays. Moreover, using GSC23 xenografted zebrafish, we found that CD146 depletion resulted in more compact delineated tumor formation and reduced tumor cell dissemination. Stem cell marker expression and neurosphere formation assays showed that CD146 increased the stem cell potential of GSCs. Furthermore, CD146 mediated radioresistance by stimulating cell survival signaling through suppression of p53 expression and activation of NF-κB. Interestingly, CD146 was also identified as an inducer of the oncogenic Yes-associated protein (YAP). In conclusion, CD146 carries out various pro-tumorigenic roles in GBM involving its cell surface receptor function, which include the stimulation of mesenchymal and invasive properties, stemness, and radiotherapy resistance, thus providing an interesting target for therapy.

CavitySpace: A Database of Potential Ligand Binding Sites in the Human Proteome.

Location and properties of ligand binding sites provide important information to uncover protein functions and to direct structure-based drug design approaches. However, as binding site detection depends on the three-dimensional (3D) structural data of proteins, functional analysis based on protein ligand binding sites is formidable for proteins without structural information. Recent developments in protein structure prediction and the 3D structures built by AlphaFold provide an unprecedented opportunity for analyzing ligand binding sites in human proteins. Here, we constructed the CavitySpace database, the first pocket library for all the proteins in the human proteome, using a widely-applied ligand binding site detection program CAVITY. Our analysis showed that known ligand binding sites could be well recovered. We grouped the predicted binding sites according to their similarity which can be used in protein function prediction and drug repurposing studies. Novel binding sites in highly reliable predicted structure regions provide new opportunities for drug discovery. Our CavitySpace is freely available and provides a valuable tool for drug discovery and protein function studies.

Associations of Obesity, Physical Activity, and Screening With State-Level Trends and Racial and Ethnic Disparities of Breast Cancer Incidence and Mortality in the US.

Importance: Breast cancer causes disproportionate disease burden among various racial and ethnic groups in the US. However, state-level temporal trends and racial and ethnic disparities and whether metabolic and lifestyle factors and screening access are associated with temporal changes remain largely unknown. Objectives: To investigate temporal trends and racial and ethnic variations at the state level and ecological correlations between obesity, physical activity, and mammography screening and breast cancer incidence and mortality trends among women in the US. Design, Setting, and Participants: A cross-sectional study was conducted to analyze breast cancer incidence and mortality trends among women in the US from January 1, 1999, to December 31, 2017, whereas an ecological analysis was performed to assess the associations. Data were analyzed from March 1, 2021, to September 30, 2021. Population-based cancer registry data were obtained from US Cancer Statistics incidence and mortality data. Prevalence of obesity, physical activity, and mammography screening were obtained from the Behavioral Risk Factor Surveillance System. Exposures: Prevalence of obesity, physical activity, and mammography screening. Main Outcomes and Measures: Breast cancer incidence and mortality trends from 1999 to 2017 in the 50 US states and the District of Columbia. Results: A total of 4 136 123 breast cancer cases and 782 454 deaths were included in the analysis, with a significant reduction in incidence (average annual percent change [AAPC], -0.4% [95% CI, -0.6% to -0.2%)]) and mortality (AAPC, -1.7% [95% CI, -1.8% to -1.5%]) during the study period. A significant state-level variation in breast cancer incidence and mortality between White women and those of other races and ethnicities was observed. A significant positive correlation was found between obesity and breast cancer incidence (r = 0.316; P = .02) and mortality (r = 0.400; P = .004) and an inverse correlation was found between physical activity and incidence (r = -0.577; P < .001) in women 55 years or older and mammography screening and mortality trends (r = -0.644; P < .001) in women 40 years or older. Conclusions and Relevance: The findings of this cross-sectional study suggest that racial and ethnic disparities exist at the state level with regard to breast cancer incidence and mortality among women in the US. Metabolic and lifestyle factors and screening access were associated with the observed trends and racial and ethnic disparities. Interventions targeting these factors may help reduce the incidence of breast cancer and related deaths.

Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy.

Background: Patients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population. Methods: A total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients' outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients' survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker. Results: Among the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066]). Conclusions: Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.

Collision Localization and Classification on the End-Effector of a Cable-Driven Manipulator Applied to EV Auto-Charging Based on DCNN-SVM.

With the increasing popularity of electric vehicles, cable-driven serial manipulators have been applied in auto-charging processes for electric vehicles. To ensure the safety of the physical vehicle-robot interaction in this scenario, this paper presents a model-independent collision localization and classification method for cable-driven serial manipulators. First, based on the dynamic characteristics of the manipulator, data sets of terminal collision are constructed. In contrast to utilizing signals based on torque sensors, our data sets comprise the vibration signals of a specific compensator. Then, the collected data sets are applied to construct and train our collision localization and classification model, which consists of a double-layer CNN and an SVM. Compared to previous works, the proposed method can extract features without manual intervention and can deal with collision when the contact surface is irregular. Furthermore, the proposed method is able to generate the location and classification of the collision at the same time. The simulated experiment results show the validity of the proposed collision localization and classification method, with promising prediction accuracy.

Research on Fast Recognition and Localization of an Electric Vehicle Charging Port Based on a Cluster Template Matching Algorithm.

With the gradual maturity of driverless and automatic parking technologies, electric vehicle charging has been gradually developing in the direction of automation. However, the pose calculation of the charging port (CP) is an important part of realizing automatic charging, and it represents a problem that needs to be solved urgently. To address this problem, this paper proposes a set of efficient and accurate methods for determining the pose of an electric vehicle CP, which mainly includes the search and aiming phases. In the search phase, the feature circle algorithm is used to fit the ellipse information to obtain the pixel coordinates of the feature point. In the aiming phase, contour matching and logarithmic evaluation indicators are used in the cluster template matching algorithm (CTMA) proposed in this paper to obtain the matching position. Based on the image deformation rate and zoom rates, a matching template is established to realize the fast and accurate matching of textureless circular features and complex light fields. The EPnP algorithm is employed to obtain the pose information, and an AUBO-i5 robot is used to complete the charging gun insertion. The results show that the average CP positioning errors (x, y, z, Rx, Ry, and Rz) of the proposed algorithm are 0.65 mm, 0.84 mm, 1.24 mm, 1.11 degrees, 0.95 degrees, and 0.55 degrees. Further, the efficiency of the positioning method is improved by 510.4% and the comprehensive plug-in success rate is 95%. Therefore, the proposed CTMA in this paper can efficiently and accurately identify the CP while meeting the actual plug-in requirements.

Iron oxide nanoparticles as a drug carrier reduce host immunosuppression for enhanced chemotherapy.

Chemotherapy is still regarded as the main modality for cancer treatment. However, it often suppresses the host immune system, resulting in limited therapeutic effects. It is desirable to design a novel chemotherapeutic agent to reduce the level of immunosuppression. Herein, we designed bovine serum albumin (BSA)-bioinspired iron oxide nanoparticles (IONPs) as a nanocarrier to load anticancer drug mitoxantrone (MTX) for enhanced chemotherapy of orthotopic breast cancer. The treatment with IONPs@BSA-MTX complexes increased CD3+CD4+ and CD3+CD8+ T lymphocytes more than free MTX. The complexes effectively restored the host immune system and exhibited a better anticancer efficacy than free MTX. It was worth noting that the BSA-inspired IONPs were a satisfactory contrast agent for magnetic resonance imaging of tumors and lymph nodes. Our work provides a novel strategy for enhanced chemotherapy with low levels of immunosuppression in the treatment of breast cancer and other cancers.

miDruglikeness: Subdivisional Drug-Likeness Prediction Models Using Active Ensemble Learning Strategies.

The drug development pipeline involves several stages including in vitro assays, in vivo assays, and clinical trials. For candidate selection, it is important to consider that a compound will successfully pass through these stages. Using graph neural networks, we developed three subdivisional models to individually predict the capacity of a compound to enter in vivo testing, clinical trials, and market approval stages. Furthermore, we proposed a strategy combing both active learning and ensemble learning to improve the quality of the models. The models achieved satisfactory performance in the internal test datasets and four self-collected external test datasets. We also employed the models as a general index to make an evaluation on a widely known benchmark dataset DEKOIS 2.0, and surprisingly found a powerful ability on virtual screening tasks. Our model system (termed as miDruglikeness) provides a comprehensive drug-likeness prediction tool for drug discovery and development.

CXCL9 Is a Potential Biomarker of Immune Infiltration Associated With Favorable Prognosis in ER-Negative Breast Cancer.

The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer.

Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN.

Notch receptors (Notch1-4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

Robust Adaptive Control of Fully Constrained Cable-Driven Serial Manipulator with Multi-Segment Cables Using Cable Tension Sensor Measurements.

The structure of the cable-driven serial manipulator (CDSM) is more complex than that of the cable-driven parallel manipulator (CDPM), resulting in higher model complexity and stronger structural and parametric uncertainties. These drawbacks challenge the stable trajectory-tracking control of a CDSM. To circumvent these drawbacks, this paper proposes a robust adaptive controller for an n-degree-of-freedom (DOF) CDSM actuated by m cables. First, two high-level controllers are designed to track the joint trajectory under two scenarios, namely known and unknown upper bounds of uncertainties. The controllers include an adaptive feedforward term based on inverse dynamics and a robust control term compensating for the uncertainties. Second, the independence of control gains from the upper bound of uncertainties and the inclusion of the joint viscous friction coefficient into the dynamic parameter vector are realised. Then, a low-level controller is designed for the task of tracking the cable tension trajectory. The system stability is analysed using the Lyapunov method. Finally, the validity and effectiveness of the proposed controllers are verified by experimenting with a three-DOF six-cable CDSM. In addition, a comparative experiment with the classical proportional-integral-derivative (PID) controller is carried out.