Deformation-Induced Crystal Growth or Redissolution, and Crystal-Induced Strengthening or Ductilization in Metallic Glasses Containing Nanocrystals.

It is generally known that the incorporation of crystals in the glass matrix can enhance the ductility of metallic glasses (MGs), at the expense of reduced strength, and that the deformation of MGs, particularly during shear banding, can induce crystal formation/growth. Here, we show that these known trends for the interplay between crystals and deformation of MGs may hold true or become inverted depending on the size of the crystals relative to the shear bands. We performed molecular dynamics simulations of tensile tests on nanocrystal-bearing MGs. When the crystals are relatively small, they bolster the strength rather than the ductility of MGs, and the crystals within a shear band undergo redissolution as the shear band propagates. In contrast, larger crystals tend to enhance ductility at the cost of strength, and the crystal volume fraction increases during deformation. These insights offer a more comprehensive understanding of the intricate relationship between deformation and crystals/crystallization in MGs, useful for fine-tuning the structure and mechanical properties of both MGs and MG-crystal composites.

Nanocomposite hyaluronic acid adhesive hydrogel with controllable drug release for bone regeneration.

Hyaluronic acid (HA) hydrogels have arisen as candidate materials to simulate the extracellular matrix and restore the functions of both cartilage and hard bones. However, integration of bone tissue adhesion and long-term osteogenic properties in one hydrogel is often ignored. Herein, a strategy to construct nanocomposite hydrogel with host tissue adhesive properties, enhanced mechanical strength, improved stability and osteogenic effects was developed. Simvastatin (SIM) was firstly incorporated into zeolitic imidazolate framework-8 (ZIF-8) and surface decoration with hydroxyapatite was realized to obtain SIM loaded and hydroxyapatite modified ZIF-8 particles (SP). As the inorganic strengthening component, SP could further cross-link the mixture of dopamine-hyaluronic acid (dHA) and tannic (TA) via coordination interaction to fabricate the hybrid adhesive hydrogel (dHA/TA/SP). Sufficient phenolic groups endowed dHA/TA/SP with excellent tissue adhesion and antibacterial properties, while incorporation of SP significantly improved the mechanical strength and stability of hydrogel. Further, due to the multiple protective effects of ZIF-8 and hydrogel, SIM was sustainably released from dHA/TA/SP. Together with the active Zn2+ and Ca2+, the expressions of ALP, OCN and RUNX2 were upregulated, and the mineralization was also promoted. With significant osteogenic effect in vitro and in vivo, this nanocomposite adhesive hydrogel holds great potential for bone defects repair.

Bionic double-crosslinked hydrogel of poly (γ-glutamic acid)/poly (N-(2-hydroxyethyl) acrylamide) with ultrafast gelling process and ultrahigh burst pressure for emergency rescue.

Injectable adhesive hydrogels combining rapid gelling with robust adhesion to wet tissues are highly required for fast hemostasis in surgical and major trauma scenarios. Inspired by the cross-linking mechanism of mussel adhesion proteins, we developed a bionic double-crosslinked (BDC) hydrogel of poly (γ-glutamic acid) (PGA)/poly (N-(2-hydroxyethyl) acrylamide) (PHEA) fabricated through a combination of photo-initiated radical polymerization and hydrogen bonding cross-linking. The BDC hydrogel exhibited an ultrafast gelling process within 1 s. Its maximum adhesion strength to wet porcine skin reached 254.5 kPa (9 times higher than that of cyanoacrylate (CA) glue) and could withstand an ultrahigh burst pressure of 626.4 mmHg (24 times higher than that of CA glue). Notably, the BDC hydrogel could stop bleeding within 10 s from a rat liver incision 10 mm long and 5 mm deep. The wound treated with the BDC hydrogel healed faster than the control groups, underlining the potential for emergency rescue and wound care scenarios.

Emerging role of gut microbiota in autoimmune diseases.

Accumulating studies have indicated that the gut microbiota plays a pivotal role in the onset of autoimmune diseases by engaging in complex interactions with the host. This review aims to provide a comprehensive overview of the existing literatures concerning the relationship between the gut microbiota and autoimmune diseases, shedding light on the complex interplay between the gut microbiota, the host and the immune system. Furthermore, we aim to summarize the impacts and potential mechanisms that underlie the interactions between the gut microbiota and the host in autoimmune diseases, primarily focusing on systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, type 1 diabetes mellitus, ulcerative colitis and psoriasis. The present review will emphasize the clinical significance and potential applications of interventions based on the gut microbiota as innovative adjunctive therapies for autoimmune diseases.

S100 protein family: Emerging role and mechanism in digestive tract cancer (Review).

Digestive tract cancer is one of the most common types of cancers globally, with ~4.8 million new cases and 3.4 million cancer­associated deaths in 2018, accounting for 26% of cancer incidence and 35% of cancer­related deaths worldwide. S100 protein family is involved in regulating cancer cell proliferation, angiogenesis, epithelial­mesenchymal transition (EMT), metastasis, metabolism and immune microenvironment homeostasis. The critical role of S100 protein family in digestive tract cancer involves complicated mechanisms, such as cancer stemness remodeling, anaerobic glycolysis regulation, tumor­associated macrophage differentiation and EMT. The present study systematically reviewed published studies on the compositions, function and the underlying molecular mechanisms of the S100 family, as well as guidance for diagnosis, treatment and prognosis of digestive tract cancer. Systematic review of the roles and underlying molecular mechanisms of S100 protein family may provide new insight into exploring potential cancer biomarkers and the optimized therapeutic strategies for digestive tract cancer.

CD300e: Emerging role and mechanism as an immune-activating receptor.

As a transmembrane protein, CD300e is primarily expressed in myeloid cells. It belongs to the CD300 glycoprotein family, functioning as an immune-activating receptor. Dysfunction of CD300e has been suggested in many diseases, such as infections, immune disorders, obesity, and diabetes, signifying its potential as a key biomarker for disease diagnosis and treatment. This review is aimed to explore the roles and potential mechanisms of CD300e in regulating oxidative stress, immune cell activation, tissue damage and repair, and lipid metabolism, shedding light on its role as a diagnostic marker or a therapeutic target, particularly for infections and autoimmune disorders.

Atomic Diffusivities of Yttrium, Titanium and Oxygen Calculated by Ab Initio Molecular Dynamics in Molten 316L Oxide-Dispersion-Strengthened Steel Fabricated via Additive Manufacturing.

Oxide-dispersion-strengthened (ODS) steels have long been viewed as a prime solution for harsh environments. However, conventional manufacturing of ODS steels limits the final product geometry, is difficult to scale up to large components, and is expensive due to multiple highly involved, solid-state processing steps required. Additive manufacturing (AM) can directly incorporate dispersion elements (e.g., Y, Ti and O) during component fabrication, thus bypassing the need for an ODS steel supply chain, the scale-up challenges of powder processing routes, the buoyancy challenges associated with casting ODS steels, and the joining issues for net-shape component fabrication. In the AM process, the diffusion of the dispersion elements in the molten steel plays a key role in the precipitation of the oxide particles, thereby influencing the microstructure, thermal stability and high-temperature mechanical properties of the resulting ODS steels. In this work, the atomic diffusivities of Y, Ti, and O in molten 316L stainless steel (SS) as functions of temperature are determined by ab initio molecular dynamics simulations. The latest Vienna Ab initio Simulation Package (VASP) package that incorporates an on-the-fly machine learning force field for accelerated computation is used. At a constant temperature, the time-dependent coordinates of the target atoms in the molten 316L SS were analyzed in the form of mean square displacement in order to obtain diffusivity. The values of the diffusivity at multiple temperatures are then fitted to the Arrhenius form to determine the activation energy and the pre-exponential factor. Given the challenges in experimental measurement of atomic diffusivity at such high temperatures and correspondingly the lack of experimental data, this study provides important physical parameters for future modeling of the oxide precipitation kinetics during AM process.

Biomimetic, self-coacervating adhesive with tough underwater adhesion for ultrafast hemostasis and infected wound healing.

Massive bleeding and wound infection due to severe traumas pose a huge threat to the life and health of sufferers; therefore, it is of clinical importance to fabricate adhesives with rapid hemostatic and superior antibacterial capabilities. However, the weak wet adhesion and insufficient function of existing bioadhesives limits their practical application. In this study, a sandcastle worm protein inspired polyelectrolyte self-coacervate adhesive of poly-γ-glutamic acid (PGA) and lysozyme (LZM) was developed. The adhesive exhibited strong underwater adhesion to various surfaces (>250 kPa for solid plates and >50 kPa for soft tissues) and maintained a 80 kPa even when soaked in water for 7 days. Rat liver and tail defect bleeding models revealed that the hemostatic efficiency was superior to that of commercial samples. The in vitro antimicrobial tests showed that the bacterial inhibition to Staphylococcus aureus and Escherichia coli reached almost 100%. Additionally, the infected wound regeneration model demonstrated that the healing rate of the adhesive group was about 100% within 15 days, which was greater than that of the control group. In vitro and in vivo experiments proved that this facilely prepared adhesive will be a promising material to fulfil the integration functions for rapid wound closure and facilitating wound healing.

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis.

Accumulating studies have implicated that circular RNAs (circRNAs) play vital roles in the pathogenesis of rheumatoid arthritis (RA). Dysregulation of macrophage polarization leads to immune homeostatic imbalance in RA. However, the altering effects and mechanisms of circRNAs on macrophages polarization and immune homeostatic balance remain largely unclear. We aimed to investigate the potential role of circRNA_17725 in RA. The high-throughput sequence was performed to identify the dysregulated circRNAs in RA. We confirmed the data by CCK-8, EdU, and Annexin V/PI staining to elucidate the proliferation and apoptosis. The expressions of M1/M2-associated markers were confirmed using real-time PCR and flow cytometry analysis. Luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) were used to demonstrate the underlying mechanism of circRNA_17725. The altering effect of circRNA_17725 on macrophages in vivo was evaluated using collagen-induced arthritis (CIA) mouse model. circRNA_17725 was demonstrated to be downregulated in peripheral blood mononuclear cells and CD14+ monocytes from RA cases in contrast to healthy controls. The negative association between circRNA_17725 and the disease activity indexes (CRP, ESR, and DAS28) was observed, suggesting a vital role of circRNA_17725 in RA disease activity. Besides, after a coexpression analysis based on high-input sequencing and the bioinformatics analysis in MiRanda and TargetScan databases, a circRNA_17725-miR-4668-5p-FAM46C competing endogenous RNA (ceRNA) network was hypothesized. A series of cytology experiments in vitro have implicated that circRNA_17725 could inhibit the proliferation but enhance the apoptosis of macrophages. Decreased expression of TNF-α, IL-1ß, and MMP-9 were observed in the supernatant of circRNA_17725-overexpressed Raw264.7 macrophages, implicating the inhibitory effect of circRNA_17725 on macrophage inflammatory mediators. Furthermore, circRNA_17725 could promote macrophage polarization towards M2 by targeting miR-4668-5p/FAM46C as a miRNA sponge. Additionally, circRNA_17725-overexpressed macrophages alleviated arthritis and protected against joint injuries and bone destruction by inducing macrophage polarization towards M2 in collagen-induced arthritis (CIA) mice. This study has suggested that circRNA_17725 regulated macrophage proliferation, apoptosis, inflammation, and polarization by sponging miR-4668-5p and upregulating FAM46C in RA.

Updated insight into the role of Th2-associated immunity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organs involvement, abundant autoantibodies, complement activation, and immune complexes depositions. By regulating inflammation and immune homeostasis, cytokines have been well documented to participate in the pathogenesis of SLE. A number of studies have shown that T helper 2 (Th2)-associated immunity plays an important role in autoimmune diseases, including SLE. Key molecules underlying Th2-related immunity are expected to serve as promising targets for the diagnosis and targeted treatment of SLE. Current progress in SLE pathogenesis and biological treatment strategies has been reviewed, focusing on the latest development in Th2-associated immunity.

Transcriptome-Wide Dynamics of m7G-Related LncRNAs during the Progression from HBV Infection to Hepatocellular Carcinoma.

BACKGROUND: The functional ramifications of internal N7-methylguanosine (m7G) modification on RNAs have recently come to light, yet its regulatory influence on long noncoding RNAs (lncRNAs) during the inflammatory-carcinogenesis transformation process in hepatitis B virus (HBV)-mediated hepatocellular carcinoma (HCC) remains largely unexplored. METHODS: Clinical surgical samples encompassing HBV-related HCC, comprising both HCC tissue (tumor group, HBV+) and corresponding adjacent liver tissue (paracancerous group, HBV+), were collected for analysis. Additional adjacent normal liver tissues (normal group, HBV-) were acquired from patients with hepatic hemangioma, serving as controls. Employing MeRIP-seq, differential m7G levels of lncRNAs across these groups were compared to identify a subset of lncRNAs exhibiting continuous and dynamic changes in m7G modification. Subsequently, in vitro validation was conducted. RESULTS: A total of 856 lncRNAs exhibited alterations in m7G modification when compared to paracancerous tissue and normal tissue. Similarly, 1775 lncRNAs displayed changes in m7G modification when comparing HCC tissue to paracancerous tissue. For intergroup comparison, orthogonal analysis revealed that 6 lncRNAs consistently demonstrated hyper-m7G modification. In vitro validation confirmed that among these 6 lncRNAs, TEKT4P2 and DNM1P41 exhibited m7G modification-dependent expression. CONCLUSIONS: This study provides a comprehensive analysis of lncRNA m7G modification during the inflammatory-carcinogenesis transformation process in HBV-mediated HCC. The findings highlight the potential for multiple lncRNAs to undergo m7G modification changes, with TEKT4P2 and DNM1P41 identified as promising molecular targets within this intricate regulatory landscape.

The Specific microRNA Profile and Functional Networks for Children with Allergic Asthma.

Background: Allergic asthma is the most common type of asthma and often occurs in early life with increasing comorbidities, including atopic dermatitis and allergic rhinitis. MicroRNAs (miRNAs) are involved in the pathogenesis of numerous immune and inflammatory disorders, particularly allergic inflammation. The specific miRNA profiles of children with allergic asthma have not been fully delineated and still require in-depth study. Objective: This study aimed to identify the expression profile of miRNAs and constructed a network of the interactions between differentially expressed miRNAs and target mRNAs to provide novel insights into understanding the pathogenesis of allergic asthma. Materials and Methods: In this study, we performed high-throughput sequencing of peripheral blood mononuclear cells (PBMCs) from children in the acute phase of asthma. Bioinformatics approaches, including miRanda, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were employed to predict novel therapeutic and diagnostic targets for allergic asthma. Real-time quantitative PCR was conducted to detect the expression of aberrantly expressed miRNAs. Results: One hundred and sixty-one differentially expressed miRNAs were identified in children with allergic asthma, including 140 conserved miRNAs and 21 novel miRNAs. A total of 8929 targeted mRNAs (44,186 transcripts) associated with differentially expressed miRNAs were predicted and significantly enriched in the cGMP-PKG signalling pathway, cholinergic synapse, and salivary secretion. We also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway and was involved in the pathogenesis of allergic asthma. Conclusion: We identified the miRNA profile of PBMCs in children with allergic asthma and also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway, which provides a novel insight into understanding the pathogenesis of allergic asthma and investigating new targets for the treatment of allergic asthma in children.

Emerging role of non-coding RNAs in glucose metabolic reprogramming and chemoresistance in colorectal cancer.

Metabolic reprogramming plays a critical role in colorectal cancer (CRC). It contributes to CRC by shaping metabolic phenotypes and causing uncontrolled proliferation of CRC cells. Glucose metabolic reprogramming is common in carcinogenesis and cancer progression. Growing evidence has implicated the modifying effects of non-coding RNAs (ncRNAs) in glucose metabolic reprogramming and chemoresistance in CRC. In this review, we have summarized currently published studies investigating the role of ncRNAs in glucose metabolic alterations and chemoresistance in CRC. Elucidating the interplay between ncRNAs and glucose metabolic reprogramming provides insight into exploring novel biomarkers for the diagnosis and prognosis prediction of CRC.

Direct transformation of equilateral hexagonal Frank vacancy loops to stacking fault tetrahedra under thermal fluctuation.

Stacking fault tetrahedra (SFTs) are highly interesting three-dimensional vacancy defects in quenched, plastically deformed or irradiated face-centered-cubic metals and have a significant impact on the properties and subsequent microstructural evolution of the materials. Their formation mechanism and stability relative to two-dimensional vacancy loops are still debated. Equilateral hexagonal Frank vacancy loops (faulted, sessile) observed in microscopy have been considered unable to directly transform to SFTs due to separation of Shockley partial dislocations as well as embryonic stacking faults. Here using sufficiently long (up to tens of nanoseconds) molecular dynamic simulations, we demonstrate that such a transformation can in fact take place spontaneously at elevated temperatures under thermal fluctuation, reducing potential energy of defected atoms by <0.05 eV/atom. The transformation becomes easier with increasing temperature or decreasing loop size.

Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy.

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota α and ß diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (Clostridium, Eubacterium, and Roseburia intestinalis) and potential probiotics (Lachnospira and Intestinibacter) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, Clostridium sp. 26_22 was negatively associated with serum creatinine (P < 0.05). DN patients could be accurately distinguished from CON by Clostridium sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and Clostridium sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by Pseudomonadales, Fusobacterium varium, and Prevotella sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. IMPORTANCE Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms.

Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice.

Previous studies have implicated that the transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) effectively alleviates systemic lupus erythematosus (SLE) primarily due to immunomodulatory effects. However, little is known about the role of hUC-MSC-derived exosomes in SLE. This study is carried out to investigate the modifying effects of hUC-MSC-exosomes on the differentiation and function of immune cells in SLE. hUC-MSC-derived exosomes were extracted from the cultural supernatant of hUC-MSCs by ultrahigh speed centrifugation. Quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and flow cytometry were performed to estimate the effect of hUC-MSC-derived exosomes on macrophage and regulatory T cell (Treg) polarization. In vivo, hUC-MSC-exosomes were injected intravenously into 28-week-old MRL/lpr mice. We had found that exosomes derived from hUC-MSC restrained the proliferation and inflammation of macrophages in vitro. Besides, MSC-exosomes inhibited CD68+M1 and HLA-DR+M1 but promoted CD206+M2 and CD163+M2 in vitro. Moreover, MRL/lpr mice administrated by intravenous injection of MSC-exosomes had less infiltration of CD14+CD11c+M1 cells but more CD14+CD163+M2 cells as well as Tregs in spleens compared with those in MRL/lpr mice treated by PBS. Additionally, MSC-exosomes could alleviate nephritis, liver and lung injuries of MRL/lpr mice. The survival of lupus mice could be improved after MSC-exosome treatment. This study has suggested that MSC-derived exosomes exert anti-inflammatory and immunomodulatory effects in SLE. MSC-exosomes ameliorate nephritis and other key organ injuries by inducing M2 macrophages and Tregs polarization. As natural nanocarriers, MSC-exosomes may serve as a promising cell-free therapeutic strategy for SLE.Abbreviations: SLE: Systemic lupus erythematosus; hUC-MSCs: Human umbilical cord mesenchymal stem cells; MSCs: Mesenchymal stem cells; qRT-PCR: Quantitative real-time polymerase chain reaction; ELISA: Enzyme-linked immunosorbent assay; Tregs: Regulatory cells; TNF-α: Tumor necrosis factor alfa; IL: Interleukin; COVID-19: Coronavirus disease 2019; pTHP-1: PMA-induced THP-1 macrophages; TEM: Transmission electron microscopy; LPS: Lipopolysaccharide; EVs: Extracellular vesicles; TRAF1: Tumor necrosis factor receptor-associated factor 1; IRAK1: Interferon-α-interleukin-1 receptor-associated kinase 1; NF-κB: Nuclear factor-κB; BLyS: B lymphocyte stimulator; APRIL: A proliferation-inducing ligand.

Immobilization of Glycogen Synthase Kinase-3ß Inhibitor on 316L Stainless Steel via Polydopamine to Accelerate Endothelialization.

The coverage of stents with healthy endothelium is crucial to the success of cardiovascular stent implantation. Immobilizing bioactive molecules on stents is an effective strategy to generate such stents. Glycogen synthase kinase-3ß inhibitor (GSKi) is a bioactive molecule that can effectively accelerate vascular endothelialization. In this work, GSKi was covalently conjugated on 316L stainless steel through polydopamine to develop a stable bioactive surface. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and water contact angle results revealed the successful introduction of GSKi onto 316L stainless steel. The GSKi coating did not obviously affect the hemocompatibility of plates. The adhesion and proliferation of human coronary artery endothelial cells (HCAECs) on stainless steel was significantly promoted by the addition of GSKi. In summary, this work provides a universal and stable strategy of immobilizing GSKi on the stent surface. This method has the potential for widespread application in the modification of vascular stents.

Immunomodulatory Effect of MSCs and MSCs-Derived Extracellular Vesicles in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disease with unclear etiology and pathogenesis. Mesenchymal stem cell (MSC) and MSC derived extracellular vesicles (EVs) play important roles in regulating innate and adaptive immunity, which are involved in many physiological and pathological processes and contribute to the immune homeostasis in SLE. The effects of MSCs and EVs on SLE have been drawing more and more attention during the past few years. This article reviews the immunomodulatory effects and underlying mechanisms of MSC/MSC-EVs in SLE, which provides novel insight into understanding SLE pathogenesis and guiding the biological therapy.

The variants at FLNA and FLNB contribute to the susceptibility of hypertension and stroke with differentially expressed mRNA.

BACKGROUND: Filamin A and filamin B were involved in vascular development and remodeling. Herein, it is important to explore the associations of FLNA and FLNB variants with hypertension and stroke. METHODS: The associations of two single-nucleotide polymorphisms (SNPs) at FLNA and five SNPs at FLNB with hypertension and stroke were examined in two case-control studies and a cohort study in Chinese Han population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by Logistic and Cox regression analysis respectively. In addition, filamin B, FLNA and FLNB mRNA expression were measured. RESULTS: In the case-control study of hypertension, FLNA rs2070816 (CT + TT vs. CC) and rs2070829 (CG + GG vs. CC) were significantly associated with hypertension in <55 years group (OR = 1.338, P = 0.018; OR = 1.615, P = 0.005) and FLNB rs839240 (AG + GG vs. AA) was significantly associated with hypertension in females (OR = 0.828, P = 0.041) and nonsmokers (OR = 0.829, P = 0.020). In the follow-up study, rs2070829 GG genotype carriers presented a higher risk of hypertension than CC/CG in males (HR = 1.737, P = 0.014) and smokers (HR = 1.949, P = 0.012). In the case-control study of stroke, FLNB rs1131356 variation was significantly associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH), ORs of additive model were 1.342 and 1.451, with P values of 0.001 and 0.007. The FLNA transcript 2, FLNB transcript 3, transcript 4 mRNA, and filamin B expression levels were significantly different between IS cases and hypertension controls and among the genotypes of rs839240 in hypertensive individuals (P < 0.05). CONCLUSIONS: Our findings support the genetic contribution of FLNA and FLNB to hypertension, and stroke with differentially mRNA expression.