Higher-Order Topological In-Bulk Corner State in Pure Diffusion Systems.

Compared with conventional topological insulator that carries topological state at its boundaries, the higher-order topological insulator exhibits lower-dimensional gapless boundary states at its corners and hinges. Leveraging the form similarity between Schrödinger equation and diffusion equation, research on higher-order topological insulators has been extended from condensed matter physics to thermal diffusion. Unfortunately, all the corner states of thermal higher-order topological insulator reside within the band gap. Another kind of corner state, which is embedded in the bulk states, has not been realized in pure diffusion systems so far. Here, we construct higher-dimensional Su-Schrieffer-Heeger models based on sphere-rod structure to elucidate these corner states, which we term "in-bulk corner states." Because of the anti-Hermitian properties of diffusive Hamiltonian, we investigate the thermal behavior of these corner states through theoretical calculation, simulation, and experiment. Furthermore, we study the different thermal behaviors of in-bulk corner state and in-gap corner state. Our results would open a different gate for diffusive topological states and provide a distinct application for efficient heat dissipation.

Correlation of serum matrix metalloproteinase 3 with osteoporosis in patients of postmenopausal rheumatoid arthritis.

Osteoporosis (OP) is a common complication of postmenopausal women with rheumatoid arthritis (RA). Herein, the objective of our study was to explore the correlation between serum matrix metalloproteinase 3 (MMP3) and OP among postmenopausal women with RA to foster better diagnosis and treatment. A total of 208 elderly postmenopausal women with RA were included in this study, with 83 patients diagnosed with OP after RA diagnosis and 125 patients without OP. Serum MMP3 levels and bone mineral density (BMD) were measured and compared. The predictive value of serum MMP3 for OP in this population was also analyzed using receiver operating curve (ROC) analysis. Postmenopausal women with RA and OP diagnosis had markedly higher serum MMP3 levels, compared to those without OP. ROC analysis showed that serum MMP3 had predictive value for OP. Additionally, a negative correlation was observed between serum MMP3 levels and BMD. High serum MMP3 levels were also found to be associated with high abnormal bone metabolism. We found that serum MMP3 levels are strongly correlated with OP in postmenopausal women with RA and that elevated levels of serum MMP3 are linked to low BMD and high abnormal bone metabolism. Serum MMP3 may be a useful biomarker for predicting OP in this population, and could potentially aid in the development of targeted prevention and treatment strategies.

Observation of parity-time symmetry in diffusive systems.

Phase modulation has scarcely been mentioned in diffusive physical systems because the diffusion process does not carry the momentum like waves. Recently, non-Hermitian physics provides a unique perspective for understanding diffusion and shows prospects in thermal phase regulation, exemplified by the discovery of anti-parity-time (APT) symmetry in diffusive systems. However, precise control of thermal phase remains elusive hitherto and can hardly be realized, due to the phase oscillations. Here we construct the PT-symmetric diffusive systems to achieve the complete suppression of thermal phase oscillation. The real coupling of diffusive fields is readily established through a strong convective background, and the decay-rate detuning is enabled by thermal metamaterial design. We observe the phase transition of PT symmetry breaking with the symmetry-determined amplitude and phase regulation of coupled temperature fields. Our work shows the existence of PT symmetry in dissipative energy exchanges and provides unique approaches for harnessing the mass transfer of particles, wave dynamics in strongly scattering systems, and thermal conduction.

Observation of non-Hermitian skin effect in thermal diffusion.

The paradigm shift of Hermitian systems into the non-Hermitian regime profoundly modifies inherent property of the topological systems, leading to various unprecedented effects such as the non-Hermitian skin effect (NHSE). In the past decade, the NHSE has been demonstrated in quantum, optical and acoustic systems. Beside those wave systems, the NHSE in diffusive systems has not yet been observed, despite recent abundant advances in the study of topological thermal diffusion. In this work, we design a thermal diffusion lattice based on a modified Su-Schrieffer-Heeger model and demonstrate the diffusive NHSE. In the proposed model, the asymmetric temperature field coupling inside each unit cell can be judiciously realized by appropriate configurations of structural parameters. We find that the temperature fields trend to concentrate toward the target boundary which is robust against initial excitation conditions. We thus experimentally demonstrated the NHSE in thermal diffusion and verified its robustness against various defects. Our work provides a platform for exploration of non-Hermitian physics in the diffusive systems, which has important applications in efficient heat collection, highly sensitive thermal sensing and others.

Contamination Status and Acute Dietary Exposure Assessment of Paralytic Shellfish Toxins in Shellfish in the Dalian Area of the Yellow-Bohai Sea, China.

The Yellow-Bohai Sea is an important semi-enclosed continental shelf marginal seas with an intensive aquaculture industry in China. The current study analyzed the contamination status and the time variations of paralytic shellfish toxins (PSTs) in shellfish between 2019 and 2020 from the Yellow-Bohai Sea in the Dalian area and estimated the acute health risks to consumers in China. A total of 199 shellfish samples (including 34 Pacific oysters, 25 Mediterranean blue mussels, 34 Manila clams, 36 bay scallops, 34 veined rapa whelks and 36 bloody clams) were analyzed from four representative aquaculture zones around the Yellow-Bohai Sea in Dalian. Among the samples, scallops and blood clams were the shellfish species with the highest detection rate of PSTs (94.4%), and the highest level of PSTs was detected in scallops with 3953.5 µg STX.2HCl eq./kg (µg STX.2HCL equivalents per kg shellfish tissue), followed by blood clams with 993.4 µg STX.2HCl eq./kg. The contents of PSTs in shellfish showed a time variation trend, and autumn was the season of concern for PST contamination in Dalian. For general Chinese consumers, the probability of acute health risks to shellfish consumers from dietary exposure to PSTs was around 13%. For typical consumers in coastal areas of China, especially those with higher shellfish intake, there was an acute health risk associated with exposure to PSTs through shellfish consumption during the occurrence of harmful algal blooms. It is suggested that the government continue to strengthen the monitoring of the source of PSTs and the monitoring of harmful algal blooms and give reasonable advice on shellfish consumption for consumers in coastal areas, such as not eating scallop viscera.

Gemcitabine Inhibits the Progression of Pancreatic Cancer by Restraining the WTAP/MYC Chain in an m6A-Dependent Manner.

PURPOSE: Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear. MATERIALS AND METHODS: We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms' tumor 1-associated protein (WTAP) and MYC. RESULTS: Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the "writer" WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the "reader" IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression. CONCLUSION: Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

Nonreciprocal Heat Circulation Metadevices.

Thermal nonreciprocity typically stems from nonlinearity or spatiotemporal variation of parameters. However, constrained by the inherent temperature-dependent properties and the law of mass conservation, previous works have been compelled to treat dynamic and steady-state cases separately. Here, by establishing a unified thermal scattering theory, the creation of a convection-based thermal metadevice which supports both dynamic and steady-state nonreciprocal heat circulation is reported. The nontrivial dependence between the nonreciprocal resonance peaks and the dynamic parameters is observed and the unique nonreciprocal mechanism of multiple scattering is revealed at steady state. This mechanism enables thermal nonreciprocity in the initially quasi-symmetric scattering matrix of the three-port metadevice and has been experimentally validated with a significant isolation ratio of heat fluxes. The findings establish a framework for thermal nonreciprocity that can be smoothly modulated for dynamic and steady-state heat signals, it may also offer insight into other heat-transfer-related problems or even other fields such as acoustics and mechanics.

The quantitative pyrrole protection of l-phenylalanine/l-phenylalaninol in aqueous media and rationally updating the mechanisms of the Clauson-Kaas reaction through DFT study.

The classical Paal-Knorr reaction is a prominent tool that can be adopted under biocompatible conditions covering various γ-dicarbonyls for either chemical biology or drug discovery. Meanwhile, the relatively mild conditions for larger molecules within biological systems have not been employed to obtain N-substituted pyrrole derivatives from simpler chiral amino acids/alcohols. The Clauson-Kaas methodology of a standard two-phase acidic mixture buffered with acetate salts was generally required for the time-consuming catalytic condensation of 2,5-dimethoxytetrahydrofuran and fast removal of pyrrolyl products after formation to inhibit their racemization. To achieve a large amount of tethered pyrrole pendants based on l-phenylalanine to construct bioactive ureas as ASK1 and PI3K inhibitors, one quick and highly efficient protocol was realized in an almost neutral and benign aqueous condition. This protocol proceeds within only 15 minutes at 90 °C, achieving nearly quantitative conversion to the final pyrrolyl product via convenient and facile column-free purification. The detailed mechanistic studies by DFT method proposed a new series involving the pathway by the initiation of a zwitterionic species/intermediate for a subsequently much more efficient self-driven pyrrole-formation. This was inconsistent with the traditional kinetic modelling of ring opening to furnish a carbocation, or the utilization of succinaldehyde/dihydroxytetrahydrofuran as a dialdehyde synthetic equivalent. In addition to the relationally neighbouring intramolecular catalytic effect from the amino acid, the crucial "H-bridge" interplay of water, along with the suggestion of a biomimetic route features similar to the N-glycosylation of carbohydrates, probably indicates the totally different reaction courses. The auto-catalysis ability of l-phenylalanine was also extensively investigated by comparisons on the details relating to l-phenylalaninol.

Recent Advances of Graphene Quantum Dots in Chemiresistive Gas Sensors.

Graphene quantum dots (GQDs), as 0D graphene nanomaterials, have aroused increasing interest in chemiresistive gas sensors owing to their remarkable physicochemical properties and tunable electronic structures. Research on GQDs has been booming over the past decades, and a number of excellent review articles have been provided on various other sensing principles of GQDs, such as fluorescence-based ion-sensing, bio-sensing, bio-imaging, and electrochemical, photoelectrochemical, and electrochemiluminescence sensing, and therapeutic, energy and catalysis applications. However, so far, there is no single review article on the application of GQDs in the field of chemiresistive gas sensing. This is our primary inspiration for writing this review, with a focus on the chemiresistive gas sensors reported using GQD-based composites. In this review, the various synthesized strategies of GQDs and its composites, gas sensing enhancement mechanisms, and the resulting sensing characteristics are presented. Finally, the current challenges and future prospects of GQDs in the abovementioned application filed have been discussed for the more rational design of advanced GQDs-based gas-sensing materials and innovative gas sensors with novel functionalities.

An Interactive Framework of Cross-Lingual NLU for In-Vehicle Dialogue.

As globalization accelerates, the linguistic diversity and semantic complexity of in-vehicle communication is increasing. In order to meet the needs of different language speakers, this paper proposes an interactive attention-based contrastive learning framework (IABCL) for the field of in-vehicle dialogue, aiming to effectively enhance cross-lingual natural language understanding (NLU). The proposed framework aims to address the challenges of cross-lingual interaction in in-vehicle dialogue systems and provide an effective solution. IABCL is based on a contrastive learning and attention mechanism. First, contrastive learning is applied in the encoder stage. Positive and negative samples are used to allow the model to learn different linguistic expressions of similar meanings. Its main role is to improve the cross-lingual learning ability of the model. Second, the attention mechanism is applied in the decoder stage. By articulating slots and intents with each other, it allows the model to learn the relationship between the two, thus improving the ability of natural language understanding in languages of the same language family. In addition, this paper constructed a multilingual in-vehicle dialogue (MIvD) dataset for experimental evaluation to demonstrate the effectiveness and accuracy of the IABCL framework in cross-lingual dialogue. With the framework studied in this paper, IABCL improves by 2.42% in intent, 1.43% in slot, and 2.67% in overall when compared with the latest model.

Quartz Nonadherent and Clean Exfoliation of the Heteroatom-Doped Bulk Carbon Nanotubes Array.

Vertically aligned carbon nanotubes array offers unique properties for various applications. Detaching them from the growth substrate, while preserving their vertical structure, is essential. Quartz, a cost-effective alternative to silicon wafers and metal-based substrates, can serve as both a reaction chamber and a growth substrate. However, the strong adhesive interaction with the quartz substrate remains an obstacle for further applications. Herein, we presented a simple and well-controlled exfoliation strategy assisted by the introduction of heteroatoms at root ends of a carbon nanotubes array. This strategy forms lower surface polarity of the carbon fragment to significantly reduce adhesion to the quartz substrate, which contributes to the effortless exfoliation. Furthermore, this scalable approach enables potential mass production on recyclable quartz substrates, enhancing the cost-effectiveness and efficiency. This work can establish a solid foundation for cost-competitive carbon nanotube-based technologies, offering a promising avenue for their widespread applications.

Design and Development of a Hair-like Sensor with Bridge-Type Flexible Amplification Mechanisms.

Compared with lever-type amplification mechanisms, bridge-type flexible amplification mechanisms have advantages in terms of amplification ratio and structural compactness. Therefore, they can effectively replace the lever-type amplification mechanism in the existing hair-like sensors and realize the development of miniature hair-like sensors with high sensitivity. With that in mind, a highly sensitive hair-like sensor based on a bridge-type amplification mechanism with distributed flexibility is presented to measure the airflow rate. First, the structural composition and operating principle of the hair-like sensor are described. Then, detailed design and analysis of the hair-like sensor are carried out, focusing on the design of the hair post structure, amplification mechanism, and resonator. Furthermore, the designed hair-like sensor is processed and prepared, and some experimental studies are conducted. The experimental results demonstrate that the developed hair-like sensor can measure the airflow rate with high sensitivity up to 8.56 Hz/(m/s)2. This provides a new concept for the structural design of hair-like sensors and expands the application of bridge-type flexible amplification mechanisms in the field of micro/nano sensors.

Combination of RUNX1 inhibitor and gemcitabine mitigates chemo-resistance in pancreatic ductal adenocarcinoma by modulating BiP/PERK/eIF2α-axis-mediated endoplasmic reticulum stress.

BACKGROUND: Gemcitabine (GEM)-based chemotherapy is the first-line option for pancreatic ductal adenocarcinoma (PDAC). However, the development of drug resistance limits its efficacy, and the specific mechanisms remain largely unknown. RUNX1, a key transcription factor in hematopoiesis, also involved in the malignant progression of PDAC, but was unclear in the chemoresistance of PDAC. METHODS: Comparative analysis was performed to screen GEM-resistance related genes using our single-cell RNA sequencing(scRNA-seq) data and two public RNA-sequencing datasets (GSE223463, GSE183795) for PDAC. The expression of RUNX1 in PDAC tissues was detected by qRT-PCR, immunohistochemistry (IHC) and western blot. The clinical significance of RUNX1 in PDAC was determined by single-or multivariate analysis and survival analysis. We constructed the stably expressing cell lines with shRUNX1 and RUNX1, and successfully established GEM-resistant cell line. The role of RUNX1 in GEM resistance was determined by CCK8 assay, plate colony formation assay and apoptosis analysis in vitro and in vivo. To explore the mechanism, we performed bioinformatic analysis using the scRNA-seq data to screen for the endoplasm reticulum (ER) stress signaling that was indispensable for RUNX1 in GEM resistance. We observed the cell morphology in ER stress by transmission electron microscopy and validated RUNX1 in gemcitabine resistance depended on the BiP/PERK/eIF2α pathway by in vitro and in vivo oncogenic experiments, using ER stress inhibitor(4-PBA) and PERK inhibitor (GSK2606414). The correlation between RUNX1 and BiP expression was assessed using the scRNA-seq data and TCGA dataset, and validated by RT-PCR, immunostaining and western blot. The mechanism of RUNX1 regulation of BiP was confirmed by ChIP-PCR and dual luciferase assay. Finally, the effect of RUNX1 inhibitor on PDAC was conducted in vivo mouse models, including subcutaneous xenograft and patient-derived xenograft (PDX) mouse models. RESULTS: RUNX1 was aberrant high expressed in PDAC and closely associated with GEM resistance. Silencing of RUNX1 could attenuate resistance in GEM-resistant cell line, and its inhibitor Ro5-3335 displayed an enhanced effect in inhibiting tumor growth, combined with GEM treatment, in PDX mouse models and GEM-resistant xenografts. In detail, forced expression of RUNX1 in PDAC cells suppressed apoptosis induced by GEM exposure, which was reversed by the ER stress inhibitor 4-PBA and PERK phosphorylation inhibitor GSK2606414. RUNX1 modulation of ER stress signaling mediated GEM resistance was supported by the analysis of scRNA-seq data. Consistently, silencing of RUNX1 strongly inhibited the GEM-induced activation of BiP and PERK/eIF2α signaling, one of the major pathways involved in ER stress. It was identified that RUNX1 directly bound to the promoter region of BiP, a primary ER stress sensor, and stimulated BiP expression to enhance the reserve capacity for cell adaptation, which in turn facilitated GEM resistance in PDAC cells. CONCLUSIONS: This study identifies RUNX1 as a predictive biomarker for response to GEM-based chemotherapy. RUNX1 inhibition may represent an effective strategy for overcoming GEM resistance in PDAC cells.

Analytical Method Optimization of Tetrodotoxin and Its Contamination in Gastropods.

Tetrodotoxin (TTX) is an extremely potent marine biotoxin. An analytical method was developed for both trace contamination and extremely high levels of TTX in gastropods by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with clean-up of cation exchange solid phase extraction (SPE) in this study. The limit of detection (LOD) in the sample matrix was 0.5 µg/kg. With the calibration of a screened internal standard (validamycin, IS), the linear range was 0.1-100 ng/mL (1.5-1500 µg/kg in sample matrix) with a correlation coefficient of r2 > 0.999. The average recoveries at three spiking levels (1.5 µg/kg, 44 µg/kg, and 1500 µg/kg) were 82.6-94.4% with relative standard deviations (RSDs) less than 8.4%. TTX levels in seven gastropods (741 samples) were studied. The contamination and analogues in Neverita didyma (N. didyma, 565 samples collected in Zhejiang province, China, from 2016 to 2022) were first reported. The detection rate of TTX in N. didyma was 34.2%. The average concentration was 23.1 µg/kg, and the maximum value was 2327 µg/kg. The time distribution study indicated that high contaminations of TTX occurred from May to August for N. didyma.

YTHDC2 inhibits rat bone mesenchymal stem cells osteogenic differentiation by accelerating RUNX2 mRNA degradation via m6A methylation.

As the most abundant internal mRNA modification, N6-methyladenosine (m6A) RNA methylation has been found to influence many biological events including bone mesenchymal stem cells (BMSCs) osteogenic differentiation. YTH N6-methyladenosine RNA binding protein C2 （YTHDC2） is an m6A reading protein with the ability to mediate the decay of combined methylated mRNA, however its role in BMSCs osteogenic differentiation remains unknown. In this study, we first found an increase of RUNX family transcription factor 2 （RUNX2） expression and a decrease of YTHDC2 expression during the process of BMSCs osteogenic differentiation. Furthermore, we transfected BMSCs with YTHDC2 interference fragment, resulting in an increased content of RUNX2 mRNA and protein inside BMSCs. Finally, through RNA Immunoprecipitation experiments, we confirmed that YTHDC2 protein can bind to RUNX2 mRNA and accelerate its decomposition. Moreover, the immunofluorescence staining also showed a negative correlation between YTHDC2 and RUNX2. In conclusion, during BMSCs osteogenic differentiation, YTHDC2 protein showed decreased expression, resulting in a higher level of RUNX2 (mRNA and protein) expression inside cells, indicating YTHDC2 as a promising molecular target for the regulation of BMSCs osteogenic differentiation.

Differentiation Between Phyllodes Tumors and Fibroadenomas of Breast Using Mammography-based Machine Learning Methods: A Preliminary Study.

OBJECTIVE: To investigate the diagnostic performance of a mammography-based radiomics model for distinguishing phyllodes tumors (PTs) from fibroadenomas (FAs) of the breast. MATERIALS AND METHODS: A total of 156 patients were retrospectively included (75 with PTs, 81 with FAs) and divided into training and validation groups at a ratio of 7:3. Radiomics features were extracted from craniocaudal and mediolateral oblique images. The least absolute shrinkage and selection operator (LASSO) algorithm and principal component analysis (PCA) were performed to select features. Three machine learning classifiers, including logistic regression (LR), K-nearest neighbor classifier (KNN) and support vector machine (SVM), were implemented in the radiomics model, imaging model and combined model. Receiver operating characteristic curves, area under the curve (AUC), sensitivity and specificity were computed. RESULTS: Among 1084 features, the LASSO algorithm selected 17 features, and PCA further selected 6 features. Three machine learning classifiers yielded the same AUC of 0.935 in the validation group for the radiomics model. In the imaging model, KNN yielded the highest accuracy rate of 89.4% and AUC of 0.947 in the validation set. For the combined model, the SVM classifier reached the highest AUC of 0.918 with an accuracy rate of 86.2%, sensitivity of 83.9%, and specificity of 89.4% in the training group. In the validation group, LR yielded the highest AUC of 0.973. The combined model had a relatively higher AUC than the radiomics model or imaging model, especially in the validation group. CONCLUSIONS: Mammography-based radiomics features demonstrate good diagnostic performance for discriminating PTs from FAs.

Insights into the roles of IL-10-producing regulatory B cells in cardiovascular disorders: recent advances and future perspectives.

Interleukin-10-producing regulatory B (B10) cells mediate the immunomodulatory functions of biosystems by secreting anti-inflammatory factors, thus playing vital roles in cardiovascular diseases such as viral myocarditis, myocardial infarction, and ischemia-reperfusion injury. However, several challenges hinder B10 cells from regulating the immunoreactivity of organisms in specific cardiovascular diseases, such as atherosclerotic disease. Regarding the regulatory mechanisms of B10 cells, the interplay between B10 cells and the cardiovascular and immune systems is complex and requires clarification. In this study, we summarize the roles of B10 cells in bacterial and aseptic heart injuries, address their regulatory functions in different stages of cardiovascular disorders, and discuss their challenges and opportunities in addressing cardiovascular diseases from bench to bedside.

Comparative analysis of the gut microbiota of wild adult rats from nine district areas in Hainan, China.

BACKGROUND: Wild rats have the potential to hold zoonotic infectious agents that can spread to humans and cause disease. AIM: To better understand the composition of gut bacterial communities in rats is essential for preventing and treating such diseases. As a tropical island located in the south of China, Hainan province has abundant rat species. Here, we examined the gut bacterial composition in wild adult rats from Hainan province. METHODS: Fresh fecal samples were collected from 162 wild adult rats, including three species (Rattus norvegicus, Leopoldamys edwardsi, and Rattus losea), from nine regions of Hainan province between 2017-2018. RESULTS: We analyzed the composition of gut microbiota using the 16S rRNA gene amplicon sequencing. We identified 4903 bacterial operational taxonomic units (30 phyla, 175 families, and 498 genera), which vary between samples of different rat species in various habitats at various times of the year. In general, Firmicutes were the most abundant phyla, followed by Bacteroidetes (15.55%), Proteobacteria (6.13%), and Actinobacteria (4.02%). The genus Lactobacillus (20.08%), unidentified_Clostridiales (5.16%), Romboutsia (4.33%), unidentified_Ruminococcaceae (3.83%), Bacteroides (3.66%), Helicobacter (2.40%) and Streptococcus (2.37%) were dominant. CONCLUSION: The composition and abundance of the gut microbial communities varied between rat species and locations. This work provides fundamental information to identify microbial communities useful for disease control in Hainan province.

Association of carotid intima-media thickness with periodontitis may depend on glycemic control.

BACKGROUND: There is evidence indicating that atherosclerosis is associated with periodontitis, especially in those with diabetes. The purpose of the present study was to determine whether glycemic control influences such association. METHODS: Cross-sectional data on 214 patients diagnosed with type 2 diabetes mellitus were obtained including results of basic laboratory tests, a periodontal examination, and carotid measurements. The association of periodontal parameters and carotid intima-media thickness (cIMT) or carotid plaque (CP) was evaluated in subgroups. RESULTS: Mean cIMT was significantly correlated with mean PLI, mean BI or number of PD ≥4 mm in the whole sample and the group with poor glycemic control. In the group with good glycemic control, however, only the number of PD ≥4 mm was associated with mean cIMT. A multiple logistic regression analysis also revealed that each 1 increase in mean PLI, mean BI or number of PD ≥4 mm was correlated with an increased cIMT in the whole sample. CONCLUSIONS: In addition to confirming the relationship between periodontitis and atherosclerosis, our study found a stronger association in groups with poor glycemic control compared to those with good glycemic control, suggesting that blood glucose modifies the association between periodontitis and arterial injury.

Fisetin treatment alleviates kidney injury in mice with diabetes-exacerbated atherosclerosis through inhibiting CD36/fibrosis pathway.

Diabetes-related vascular complications include diabetic cardiovascular diseases (CVD), diabetic nephropathy (DN) and diabetic retinopathy, etc. DN can promote the process of end-stage renal disease. On the other hand, atherosclerosis accelerates kidney damage. It is really an urge to explore the mechanisms of diabetes-exacerbated atherosclerosis as well as new agents for treatment of diabetes-exacerbated atherosclerosis and the complications. In this study we investigated the therapeutic effects of fisetin, a natural flavonoid from fruits and vegetables, on kidney injury caused by streptozotocin (STZ)-induced diabetic atherosclerosis in low density lipoprotein receptor deficient (LDLR-/-) mice. Diabetes was induced in LDLR-/- mice by injecting STZ, and the mice were fed high-fat diet (HFD) containing fisetin for 12 weeks. We found that fisetin treatment effectively attenuated diabetes-exacerbated atherosclerosis. Furthermore, we showed that fisetin treatment significantly ameliorated atherosclerosis-enhanced diabetic kidney injury, evidenced by regulating uric acid, urea and creatinine levels in urine and serum, and ameliorating morphological damages and fibrosis in the kidney. In addition, we found that the improvement of glomerular function by fisetin was mediated by reducing the production of reactive oxygen species (ROS), advanced glycosylation end products (AGEs) and inflammatory cytokines. Furthermore, fisetin treatment reduced accumulation of extracellular matrix (ECM) in the kidney by inhibiting the expression of vascular endothelial growth factor A (VEGFA), fibronectin and collagens, while enhancing matrix metalloproteinases 2 (MMP2) and MMP9, which was mainly mediated by inactivating transforming growth factor ß (TGFß)/SMAD family member 2/3 (Smad2/3) pathways. In both in vivo and in vitro experiments, we demonstrated that the therapeutic effects of fisetin on kidney fibrosis resulted from inhibiting CD36 expression. In conclusion, our results suggest that fisetin is a promising natural agent for the treatment of renal injury caused by diabetes and atherosclerosis. We reveal that fisetin is an inhibitor of CD36 for reducing the progression of kidney fibrosis, and fisetin-regulated CD36 may be a therapeutic target for the treatment of renal fibrosis.