A positive association between RDW and coronary heart disease in the rheumatoid arthritis population: A cross-sectional study from NHANES.

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036-1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55-66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.

Quantification of enlarged deep medullary vein volumes in Sturge-Weber syndrome.

Background: Enlarged deep medullary veins (EDMVs) in patients with Sturge-Weber syndrome (SWS) may channel venous blood from the surface to the deep vein system in brain regions affected by the leptomeningeal venous malformation. Thus, the quantification of EDMV volume may provide an objective imaging marker for this vascular compensatory process. The present study proposes a novel analytical method to quantify enlarged EDMV volumes in the affected hemisphere of patients with unilateral SWS. Methods: Twenty young subjects, including 10 patients with unilateral SWS and 10 healthy siblings (age 14.5±6.7 and 16.0±7.0 years, respectively) underwent 3T brain MRI scanning using susceptibility-weighted imaging (SWI) and volumetric T1-weighted sequences. The proposed image analytic steps segmented EDMVs in white matter regions, defined on the volumetric T1-weighted images, by statistically associating the likelihood of intensity, location, and tubular shape on SWI. The volumes of the segmented EDMVs, calculated in each hemisphere, were compared between affected and unaffected hemispheres. EDMV volumes were also correlated with visually assessed EDMV scores, hemispheric white matter volumes, and cortical surface areas. Parametric tests including Pearson's correlation, unpaired and paired t-tests, were used. A P value <0.05 was considered statistically significant. Results: It was found that EDMVs were identified well in SWS-affected hemispheres while calcified regions were excluded. Mean EDMV volumes in the SWS-affected hemispheres were 10-12-fold greater than in the unaffected or healthy control hemispheres; while white matter volumes and cortical surface areas were lower. EDMV volumes in the SWS-affected hemispheres showed a strong positive correlation with the visual EDMV scores (r=0.88, P=0.001) and an inverse correlation with cortical surface area ratios (r=-0.65, P=0.04) but no correlation with white matter volume ratios. Conclusions: EDMVs were detected in the SWS-affected atrophic hemispheres reliably while avoiding calcified regions. The approach can be used to quantify enlarged deep cerebral veins in the human brain, which may provide a potential marker of cerebral venous remodeling.

An updated overview of some factors that influence the biological effects of nanoparticles.

Nanoparticles (NPs) can be extremely effective in the early diagnosis and treatment of cancer due to their properties. The nanotechnology industry is developing rapidly. The number of multifunctional NPs has increased in the market and hundreds of NPs are in various stages of preclinical and clinical development. Thus, the mechanism underlying the effects of NPs on biological systems has received much attention. After NPs enter the body, they interact with plasma proteins, tumour cell receptors, and small biological molecules. This interaction is closely related to the size, shape, chemical composition and surface modification properties of NPs. In this review, the effects of the size, shape, chemical composition and surface modification of NPs on the biological effects of NPs were summarised, including the mechanism through which NPs enter cells, the resulting oxidative stress response, and the interaction with proteins. This review of the biological effects of NPs can not only provide theoretical support for the preparation of safer and more efficient NPs but also lay the foundation for their clinical application.

Recent advances in the applications of graphene materials for the oil and gas industry.

Graphene is a material formed with carbon atoms connected by sp2 hybridization. It is extremely strong and very ductile, and is superhydrophobic and superlipophilic. It has important application prospects in materials science, micro and nano processing, energy, aerospace and biomedicine. Graphene also has some applications in the petroleum industry. As nanoscale materials, graphene-based materials can plug nano-pores and prevent water intrusion into clay minerals during the drilling process, they are suitable for sliding between layers and can be used as lubricants due to the two-dimensional structure. The adsorption properties of graphene-based materials allow them to improve the treatment rate when treating oily wastewater. This paper compiles recent advances in the application of graphene and its derivatives in oilfield extraction, including improving drilling fluid performance, enhanced oil recovery and oily wastewater treatment. We compare the performance advantages of graphene-based materials over other additives, and summarize the mechanism of action of graphene-based materials. The shortcomings of current research are identified and future research and improvement directions are envisaged.

Polydopamine-containing nano-systems for cancer multi-mode diagnoses and therapies: A review.

Polydopamine (PDA) has fascinating properties such as inherent biocompatibility, simple preparation, strong near-infrared absorption, high photothermal conversion efficiency, and strong metal ion chelation, which have catalyzed extensive research in PDA-containing multifunctional nano-systems particularly for biomedical applications. Thus, it is imperative to overview synthetic strategies of various PDA-containing nanoparticles (NPs) for state-of-the-art cancer multi-mode diagnoses and therapies applications, and offer a timely and comprehensive summary. In this review, we will focus on the synthetic approaches of PDA NPs, and summarize the construction strategies of PDA-containing NPs with different structure forms. Additionally, the application of PDA-containing NPs in bioimaging such as photoacoustic imaging, fluorescence imaging, magnetic resonance imaging and other imaging modalities will be reviewed. We will especially offer an overview of their therapeutic applications in tumor chemotherapy, photothermal therapy, photodynamic therapy, photocatalytic therapy, sonodynamic therapy, radionuclide therapy, gene therapy, immunotherapy and combination therapy. At the end, the current trends, limitations and future prospects of PDA-containing nano-systems will be discussed. This review aims to provide guidelines for new scientists in the field of how to design PDA-containing NPs and what has been achieved in this area, while offering comprehensive insights into the potential of PDA-containing nano-systems used in cancer diagnosis and treatment.

Surface functionalization-dependent inflammatory potential of polystyrene nanoplastics through the activation of MAPK/ NF-κB signaling pathways in macrophage Raw 264.7.

Increasing amounts of nanoplastics (NPs) in the environment are a great threat to human health, causing intestinal inflammation when consumed through seafood and water. There is, however, still a lack of understanding of the immunomodulatory role of NPs in immune cells, especially the early signal events behind inflammation resulting from NPs ingestion. In this study, we explored the dynamic internalization of polystyrene NPs and their carboxy and amino-functionalized products (PS, PS-COOH and PS-NH2) followed by activation of ROS-MAPK/NF-κB signaling pathways in macrophage RAW 264.7. The inflammatory and cytotoxic potentials of NPs were evaluated by ELISA and apoptosis assays. Results showed that PS-COOH accumulated most in cells and induced more pronounced ROS and apoptosis than PS, PS-NH2 and PS-µm. PS-COOH and PS-NH2 showed stronger MAPK/NF-κB activation potential to at a low concentration of 10 µg/mL than unmodified PS, followed by production of IL-6 and TNF-α cytokines. Furthermore, PS-COOH induced MAPK/NF-κB activation and cytokine secretion could be inhibited by NAC, indicating that ROS was responsible for signal dysregulation and immunogenicity of PS-COOH, but not for PS-NH2. The results suggested that the MAPK and NF-κB pathways were involved in NPs-induced macrophage inflammation, which was influenced by surface functionalization of NPs, with carboxylated PS NPs exhibiting a greater pro-inflammatory and cytotoxic potential.

SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells.

Rationale: Malignant ascites in peritoneal metastases is a lipid-enriched microenvironment and is frequently involved in the poor prognosis of epithelial ovarian cancer (EOC). However, the detailed mechanisms underlying ovarian cancer (OvCa) cells dictating their lipid metabolic activities in promoting tumor progression remain elusive. Methods: The omental conditioned medium (OCM) was established to imitate the omental or ascites microenvironment. Mass spectrometry, RT-qPCR, IHC, and western blot assays were applied to evaluate human fatty acid desaturases expressions and activities. Pharmaceutical inhibition and genetic ablation of SCD1/FADS2 were performed to observe the oncogenic capacities. RNA sequencing, lipid peroxidation, cellular iron, ROS, and Mito-Stress assays were applied to examine ferroptosis. OvCa patient-derived organoid and mouse model of peritoneal metastases were used to evaluate the combined effect of SCD1/FADS2 inhibitors with cisplatin. Results: We found that two critical fatty acid desaturases, stearoyl-CoA desaturase-1 (SCD1) and acyl-CoA 6-desaturase (FADS2), were aberrantly upregulated, accelerating lipid metabolic activities and tumor aggressiveness of ascites-derived OvCa cells. Lipidomic analysis revealed that the elevation of unsaturated fatty acids (UFAs) was positively associated with SCD1/FADS2 levels and the oncogenic capacities of OvCa cells. In contrast, pharmaceutical inhibition and genetic ablation of SCD1/FADS2 retarded tumor growth, cancer stem cell (CSC) formation and reduced platinum resistance. Inhibition of SCD1/FADS2 directly downregulated GPX4 and the GSH/GSSG ratio, causing disruption of the cellular/mitochondrial redox balance and subsequently, iron-mediated lipid peroxidation and mitochondrial dysfunction in ascites-derived OvCa cells. Conclusions: Combinational treatment with SCD1/FADS2 inhibitors and cisplatin synergistically repressed tumor cell dissemination, providing a promising chemotherapeutic strategy against EOC peritoneal metastases.

Cationic Nanoparticulate System for Codelivery of MicroRNA-424 and Podophyllotoxin as a Multimodal Anticancer Therapy.

Because of the complexity of cancer ecosystems, the efficacy of single-agent chemotherapy is limited. Herein, we report the use of cationic nanoparticles (designated PPCNs) generated from a chemically modified form of the chemotherapeutic agent podophyllotoxin (PPT) to deliver both microRNA-424 (miR-424) and PPT to tumor cells, thus combining chemotherapy and gene therapy. We evaluated the optimal loading ratio of miR-424─which targets programmed cell death ligand 1 (PD-L1) mRNA and reduces PD-L1 production, thus promoting the attack of tumor cells by T cells─for effective delivery of miR-424 and PPCNs into nonsmall-cell lung cancer cells (H460). Because miR-424 can reverse chemotherapy resistance, treatment of the tumor cells with the combination of miR-424 and PPT enhanced their sensitivity to PPT. Because miR-424 and the PPCNs regulated PD-L1 production in different ways, the miR-424@PPCN complexes were significantly more efficacious than either miR-424 or PPCNs alone. We also demonstrated that treatment of tumor-bearing mice with these complexes significantly inhibited tumor growth and extended survival. Moreover, additional in vitro experiments revealed that the complexes could remodel the tumor immune microenvironment, relieve immunosuppression, and achieve immune normalization. This novel system for delivering a combination of PPT and miR-424 shows great potential for the multimodal treatment of lung cancer.

Application of "smart" multifunctional nanoprobes in tumor diagnosis and treatment.

Cancer is one of the major diseases that pose a threat to human health and life, especially because it is difficult to diagnose and cure, and recurs easily. In recent years, the development of nanotechnology has provided researchers with new tools for cancer treatment. In particular, nanoprobes that facilitate integrated diagnosis and treatment, high-resolution imaging, and accurate tumor targeting provide new avenues for the early detection and treatment of cancer. This review focuses on the preparations and applications of two kinds of "smart" multifunctional nanoprobes: "Off-On" nanoprobes and "Charge-Reversal" nanoprobes. This review also briefly discusses their mechanisms of action, as they could provide new ideas for the further development of this field.

pH-sensitive hyaluronic acid-targeted prodrug micelles constructed via a one-step reaction for enhanced chemotherapy.

Although many chemotherapy prodrugs have been developed for tumor therapy, non-targeted delivery, uncontrolled release and tedious construction procedure of prodrugs still limit their clinical application in tumor treatment. In this work, hyaluronic acid (HA) which has tumor-targeting ability was used to conjugate to antitumor drug podophyllotoxin (PPT) to construct a pH-sensitive prodrug named HA-CO-O-PPT just via a one-step esterification reaction. The HA-CO-O-PPT spontaneously assembled into nano spherical micelles in aqueous medium, which had outstanding serum stability and blood compatibility. The obtained prodrug micelles (named HP micelles) exhibited a pH-responsive drug release mode with cumulative release reaching 81.2% due to their dissociation in response to acid stimulus, and had a high cellular uptake efficiency beyond 97% owing to HA receptor-mediated targeting. Furthermore, it was found that the prodrug micelles showed excellent antitumor activities in vivo with the tumor inhibition ratio up to 85% and negligible systemic toxicity. Accordingly, the pH-responsive HP micelles constructed by a simple one-step reaction, could be a promising candidate as a chemotherapeutic agent for cancer therapy.

Self-Assembly of Podophyllotoxin-Loaded Lipid Bilayer Nanoparticles for Highly Effective Chemotherapy and Immunotherapy via Downregulation of Programmed Cell Death Ligand 1 Production.

Low drug delivery efficiency elevates the cost of medication, lowers the therapeutic efficacy, and appears as a leading reason for unmet needs in anticancer therapies. Herein, we report the development of self-assembled podophyllotoxin-loaded lipid bilayer nanoparticles that inhibit the production of programmed cell death ligand 1 in lung cancer cells and promote tumor-specific immune responses, thus offering a strategy for regulating the immunosuppressive microenvironment of tumors. In addition, encapsulation of podophyllotoxin in the nanoparticles reduced its systemic toxicity, enhanced its penetration into tumors, and increased its antitumor efficacy. Systemic injection of the nanoparticles into tumor-bearing mice not only prevented tumor immune escape but also significantly inhibited tumor growth and extended survival. In general, the podophyllotoxin-loaded nanoparticles exhibited both immunological effects and antitumor effects in addition to having better targeting activity and fewer side effects than free podophyllotoxin. We expect our findings to facilitate the development of therapies for lung cancer.

Pancreatic Cancer Progression Is Regulated by IPO7/p53/LncRNA MALAT1/MiR-129-5p Positive Feedback Loop.

Background: Pancreatic cancer is a malignancy with poor prognosis. Importin 7 (IPO7) is a soluble nuclear transport factor, which has been linked to the pathogenesis of several human diseases. However, its role and underlying mechanism in pancreatic cancer are still obscure. Methods: Immunohistochemical staining and quantitative real-time polymerase chain reaction (qPCR) were performed to determine IPO7 expression in pancreatic cancer tissues and adjacent tissues. Western blot was used to measure IPO7 expression at the protein level in cell lines. Cell Counting Kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), flow cytometry, and Transwell assays were employed to explore the biological functions of IPO7. Subcutaneous xenograft transplanted tumor model and caudal vein injection model in mice were also established to validate the oncogenic role of IPO7. Western blot and qPCR were utilized to detect the regulatory function of IPO7 on p53 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), respectively. Interaction between MALAT1 and miR-129-5p and interaction between miR-129-5p and IPO7 were verified by bioinformatics prediction, qPCR, dual-luciferase reporter gene experiment, RNA immunoprecipitation (RIP), and pull-down assay. Results: Upregulation of IPO7 in pancreatic cancer tissues was associated with adverse prognosis of the patients with pancreatic cancer. Knocking down IPO7 remarkably suppressed cancer cell proliferation and metastasis, while it promoted apoptosis. Overexpression of IPO7 facilitated the malignant phenotypes of pancreatic cancer cells. Mechanistically, IPO7 could repress the expression of p53 and induce the expression of MALAT1 but reduce miR-129-5p expression. Furthermore, miR-129-5p was identified as a posttranscriptional regulator for IPO7, and its inhibition led to IPO7 overexpression in pancreatic cancer cells. Conclusion: IPO7 is a novel oncogene for pancreatic cancer, and IPO7/p53/MALAT1/miR-129-5p positive feedback loop facilitates the progression of this deadly disease.

Tumor immunotherapy and multi-mode therapies mediated by medical imaging of nanoprobes.

Immunotherapy is an effective tumor treatment strategy that has several advantages over conventional methods such as surgery, radiotherapy and chemotherapy. Studies show that multifunctional nanoprobes can achieve multi-mode image-guided multiple tumor treatment modes. The tumor cells killed by chemotherapies or phototherapies release antigens that trigger an immune response and augment the effects of tumor immunotherapy. Thus, combining immunotherapy and multifunctional nanoprobes can achieve early cancer diagnosis and treatment. In this review, we have summarized the current research on the applications of multifunctional nanoprobes in image-guided immunotherapy. In addition, image-guided synergistic chemotherapy/photothermal therapy/photodynamic therapy and immunotherapy have also been discussed. Furthermore, the application potential and clinical prospects of multifunctional nanoprobes in combination with immunotherapy have been assessed.

A pH/ultrasonic dual-response step-targeting enterosoluble granule for combined sonodynamic-chemotherapy guided via gastrointestinal tract imaging in orthotopic colorectal cancer.

Colorectal cancer is one of the malignant tumors with high morbidity and lethality. Its efficient diagnosis and treatment has important significance. In this study, the orthotopic cancer model mouse, which could perfectly simulate clinical inflammatory colorectal cancer, was constructed by chemical induction. Based on this model, a new pH/ultrasonic dual-response, step-targeting and precisely controlled-release enteric-coated granule was designed for the combined sonodynamic (SDT)-chemotherapy. The enteric-coated granule was fabricated by enwrapping carboxymethyl chitosan (CMC) on folic acid-modified phospholipid (SLB-FA) encapsulating mesoporous silicon-coated gold nanoparticles loaded with chlorin (Ce6) and doxorubicin hydrochloride (DOX), titled as Au@mSiO2/Ce6/DOX/SLB-FA@CMC (GMCDS-FA@CMC). The diameter of the Au@mSiO2/Ce6/DOX/SLB-FA (GMCDS-FA) nanoprobe was 61.21 nm and that of the GMCDS-FA@CMC enteric-coated granule was 1.1 µm. MTT results showed that the cell survival rate was still as high as 76.55 ± 1.27% when the concentration of GMCDS-FA was up to 200 µg mL-1, which can indicate the low cytotoxicity of the nanoprobe. According to CT imaging, the enteric-coated granule had the highest concentration in the colorectum of the orthotopic cancer mouse after 7-9 h with oral administration, and was nearly metabolized out of the body after 24 h. The in vitro and in vivo experiments showed that the targeting enteric-coated granule had the best effect of treatment and desired prognosis after combined SDT-chemotherapy.

Distinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice.

Proprioceptive neurons (PNs) are essential for the proper execution of all our movements by providing muscle sensory feedback to the central motor network. Here, using deep single cell RNAseq of adult PNs coupled with virus and genetic tracings, we molecularly identify three main types of PNs (Ia, Ib and II) and find that they segregate into eight distinct subgroups. Our data unveil a highly sophisticated organization of PNs into discrete sensory input channels with distinct spatial distribution, innervation patterns and molecular profiles. Altogether, these features contribute to finely regulate proprioception during complex motor behavior. Moreover, while Ib- and II-PN subtypes are specified around birth, Ia-PN subtypes diversify later in life along with increased motor activity. We also show Ia-PNs plasticity following exercise training, suggesting Ia-PNs are important players in adaptive proprioceptive function in adult mice.

Reciprocal REGγ-mTORC1 regulation promotes glycolytic metabolism in hepatocellular carcinoma.

Despite significant progression in the study of hepatocellular carcinoma (HCC), the role of the proteasome in regulating cross talk between mTOR signaling and glycolysis in liver cancer progression is not fully understood. Here, we demonstrate that deficiency of REGγ, a proteasome activator, in mice significantly attenuates DEN-induced liver tumor formation. Ablation of REGγ increases the stability of PP2Ac (protein phosphatase 2 catalytic subunit) in vitro and in vivo, which dephosphorylates PRAS40 (AKT1 substrate 1) and stabilizes the interaction between PRAS40 and Raptor to inactive mTORC1-mediated hyper-glycolytic metabolism. In the DEN-induced animal model and clinical hepato-carcinoma samples, high levels of REGγ in HCC tumor regions contribute to reduced expression of PP2Ac, leading to accumulation of phosphorylated PRAS40 and mTORC1-mediated activation of HIF1α. Interestingly, mTORC1 enhances REGγ activity in HCC, forming a positive feedback regulatory loop. In conclusion, our study identifies REGγ-PP2Ac-PRAS40 axis as a new layer in regulating mTORC1 activity and downstream glycolytic alterations during HCC development, highlighting the REGγ-proteasome as a potential target for personalized HCC therapy.

Interaction kinetics of peptide lipids-mediated gene delivery.

BACKGROUND: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. RESULTS: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (- 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the "proton sponge effect" of the lipid. CONCLUSIONS: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

MAP30 protein from Momordica charantia is therapeutic and has synergic activity with cisplatin against ovarian cancer in vivo by altering metabolism and inducing ferroptosis.

Increasing evidence shows that Traditional Chinese Medicine (TCM) has an obvious appeal for cancer treatment, but there is still a lack of scientific investigation of its underlying molecular mechanisms. Bitter melon or bitter gourd (Momordica charantia) is an edible fruit that is commonly consumed, and it is used to cure different diseases in various ancient folk medical practices. We report that a bioactive protein, MAP30, isolated from bitter melon seeds exhibited potent anticancer and anti-chemoresistant effects on ovarian cancer cells. Functional studies revealed that MAP30 inhibited cancer cell migration, cell invasion, and cell proliferation in various ovarian cancer cells but not normal immortalized ovarian epithelial cells. When administered with cisplatin, MAP30 produced a synergistic effect on cisplatin-induced cell cytotoxicity in ovarian cancer cells. When low doses of cisplatin and MAP30 were co-injected intraperitoneally, a remarkable reduction of tumor dissemination and tumor growth was observed in an ovarian cancer ascites mouse model. Notably, blood tests confirmed that MAP30 did not cause any adverse effects on liver and kidney functions in the treated mice. MAP30 activated AMP-activated protein kinase (AMPK) signaling via CaMKKß and induced cell cycle arrest in the S-phase. MAP30 modulated cell metabolism of ovarian cancer cells via suppression of GLUT-1/-3-mediated glucose uptake, adipogenesis, and lipid droplet formation in tumor development and progression. MAP30 also induced an increase in intracellular Ca2+ ion concentration, which triggered ROS-mediated cancer cell death via apoptosis and ferroptosis. Collectively, these findings suggest that natural MAP30 is a non-toxic supplement that may enhance chemotherapeutic outcomes and benefit ovarian cancer patients with peritoneal metastases.