Elevated blood pressure: a genetically determined risk factor for cerebral artery dissection.

BACKGROUND: We aim to investigate the potential causal link between blood pressure (BP) levels and cerebral artery dissection (CAD) risk employing a two-sample Mendelian randomization (TSMR) framework. METHODS: Utilizing large-scale genome-wide association studies (GWAS)-retrieved data, we employed various MR techniques, including inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode, to ascertain BP's causal impact on CAD. The MR-Egger intercept was calculated to assess pleiotropy presence, determining heterogeneity by Cochran's Q statistic. RESULTS: The findings highlighted a significant association between elevated systolic BP (SBP; IVW: OR=3.09, 95% CI: 1.11-8.61, p=0.031) and increased diastolic BP (DBP; IVW: OR=2.17, 95% CI: 1.14-6.21, p=0.023) with CAD risk. Sensitivity analyses reinforced the robustness and reliability of these results. CONCLUSIONS: The results from this TSMR study suggest a causal link between high SBP and DBP and the increased likelihood of CAD, which provide genetic evidence for a reduced risk of CAD under blood pressure control.

Endothelial TRPV4 channel mediates the vasodilation induced by Tanshinone IIA.

Tanshinone IIA (TSA), the main lipo-soluble component from the dried rhizome of Salvia miltiorrhiza, has been shown to induce vasodilation. However, the underlying mechanisms remains unclear. This study aimed to investigate the effect of TSA on the vasodilation of small resistant arteries ex vivo. Vascular myography revealed that endothelial denudation reduced significantly the vasodilatory effect of TSA. Blocking transient receptor potential vanilloid 4 (TRPV4) channels prevented TSA-induced vasodilation. Whole-cell patch-clamp analysis revealed that the current passing through TRPV4 channels increased after TSA treatment in endothelial cells (ECs). This was attributed to reduced TRPV4 protein degradation along with its increased expression. The TRPV4 inhibitor HC-067047 lowed nitric oxide (NO) production and TSA-induced expression of endothelial nitric oxide synthase (eNOS). Moreover, it increased the production of cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG). The present results indicate that TSA induces endothelium-dependent vasodilation, which is mediated by the TRPV4-NO-PKG signaling pathway. These findings highlight the potential of TSA, a compound known in traditional Chinese medicine as Danshen (Salvia miltiorrhiza), for future cardiovascular therapeutic strategies.

Vapor-Tailored Nanojunctions in Ultraporous ZnO Nanoparticle Networks for Superior UV Photodetection.

High quality nanojunctions are known to effectively improve the conductivity and structural robustness of ultraporous nanoparticle networks, surpassing the performance of natural van der Waals interfaces. Nevertheless, the traditional approach of forming these junctions by thermal annealing is incompatible with thermolabile polymers and slender metal electrodes found in modern wearable technologies. Herein, we present a low temperature, solvent vapor-based method to rapidly elicit high-quality metal-oxide nanojunctions in a fast, effortless, inexpensive, and easily scalable process; capable of generating necked interparticle interfaces in a matter of minutes. When applied to ultraporous-based ZnO Ultraviolet (UV) photodetectors, the vapor-tailoring process produces an incredible 128,000-fold improvement in responsivity (6.6 A.W-1) over untreated structures (51.2 µA.W-1), and a 5300-fold improvement in responsivity over thermally annealed structures; all while maintaining exceptionally low dark currents of 140 pA at a low bias voltage of 1 V. Most importantly, the exceptional performance enabled by room temperature synthesis suggests high potential adaptability of this process toward wearable UV sensors, shedding lights on the strategy of modifying weakly bonded porous nanostructures for improved physical properties.

Gut microbiota dysbiosis in hyperuricaemia promotes renal injury through the activation of NLRP3 inflammasome.

BACKGROUND: The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. RESULTS: A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3-/-) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. CONCLUSION: Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.

Spontaneous Dislocation of the Lens Nucleus Into the Anterior Chamber Observed in a Patient With Overmature Senile Cataract.

Overmature cataract refers to the advanced stage of cataract where timely surgical intervention is not performed, leading to further progression characterized by decreased water content in the lens, degradation of fibers, and liquefaction within its structure, which can cause a reduction in volume, wrinkling of the capsule, as well as calcification or cholesterol crystallization on its surface. In addition, it may result in deepening of the anterior chamber. If left promptly untreated, these complications may result in visual impairment or even blindness. The occurrence of spontaneous complete dislocation of the lens nucleus into the anterior chamber in overmature cataracts is extremely uncommon. The authors present a case study involving a 74-year-old female patient who was diagnosed with complete dislocation of the lens nucleus in an overmature senile cataract without any apparent ocular injury or any relevant medical records. After undergoing cataract removal combined with anterior vitrectomy, the patient experienced relief from eye discomfort and expressed satisfaction with the surgical outcome; however, her visual acuity did not show significant improvement.

Highly Porous ZnO/CNT Hybrid Microclusters for Superior UV Photodetection.

The formation of nanoscale junctions among nanoparticles in self-assembled nanostructures is crucial for improving both interfacial conductivity and structural integrity. However, the inherent reliance on weak van der Waals forces to hold nanoparticles together poses challenges in developing commercially viable devices due to their inefficient carrier transport characteristics. This study presents the successful integration of carbon nanotubes (CNTs) into highly porous nanomicrocluster arrays of ZnO, resulting in the formation of cohesive and crack-free highly porous ZnO/CNT heterojunction films. This integration marks a significant improvement in UV photodetection performance, demonstrating a record-high photocurrent to dark current ratio of 3.3 × 106 and an exceptional responsivity of 18.5 A/W at a low bias of 0.5 V and under an ultra low light density of 25 µW/cm2. These findings underscore the efficacy of this high-performance structure as a versatile and scalable platform technology for the rapid, cost-effective fabrication of hybrid photodetectors in wearable and portable devices.

Polyacrylamide/sodium alginate/sodium chloride photochromic hydrogel with high conductivity, anti-freezing property and fast response for information storage and electronic skin.

Photochromic hydrogels have promising prospects in areas such as wearable device, information encryption technology, optoelectronic display technology, and electronic skin. However, there are strict requirements for the properties of photochromic hydrogels in practical engineering applications, especially in some extreme application environments. The preparation of photochromic hydrogels with high transparency, high toughness, fast response, colour reversibility, excellent electrical conductivity, and anti-freezing property remains a challenge. In this study, a novel photochromic hydrogel (PAAm/SA/NaCl-Mo7) was prepared by loading ammonium molybdate (Mo7) and sodium chloride (NaCl) into a dual-network hydrogel of polyacrylamide (PAAm) and sodium alginate (SA) using a simple one-pot method. PAAm/SA/NaCl-Mo7 hydrogel has excellent conductivity (175.9 S/cm), water retention capacity and anti-freezing properties, which can work normally at a low temperature of -28.4 °C. In addition, the prepared PAAm/SA/NaCl-Mo7 hydrogel exhibits fast response (<15 s), high transparency (>70 %), good toughness (maximum elongation up to 1500 %), good cyclic compression properties at high compressive strains (60 %), good biocompatibility (78.5 %), stable reversible discolouration and excellent sensing properties, which can be used for photoelectric display, information storage and motion monitoring. This work provides a new inspiration for the development of flexible electronic skin devices.

A High-Stretching, Rapid-Self-Healing, and Printable Composite Hydrogel Based on Poly(Vinyl Alcohol), Nanocellulose, and Sodium Alginate.

Hydrogels with excellent flexibility, conductivity, and controllable mechanical properties are the current research hotspots in the field of biomaterial sensors. However, it is difficult for hydrogel sensors to regain their original function after being damaged, which limits their practical applications. Herein, a composite hydrogel (named SPBC) of poly(vinyl alcohol) (PVA)/sodium alginate (SA)/cellulose nanofibers (CNFs)/sodium borate tetrahydrate was synthesized, which has good self-healing, electrical conductivity, and excellent mechanical properties. The SPBC0.3 hydrogel demonstrates rapid self-healing (<30 s) and achieves mechanical properties of 33.92 kPa. Additionally, it exhibits high tensile strain performance (4000%). The abundant internal ions and functional groups of SPBC hydrogels provide support for the good electrical conductivity (0.62 S/cm) and electrical response properties. In addition, the SPBC hydrogel can be attached to surfaces such as fingers and wrists to monitor human movements in real time, and its good rheological property supports three-dimensional (3D) printing molding methods. In summary, this study successfully prepared a self-healing, conductive, printable, and mechanically superior SPBC hydrogel. Its suitability for 3D-printing personalized fabrication and outstanding sensor properties makes it a useful reference for hydrogels in wearable devices and human motion monitoring.

New nanosensor fabricated on single nanopore electrode filled with prussian blue and graphene quantum dots coated by polypyrrole for hydrogen peroxide sensing.

Hydrogen peroxide (H2O2) is a common oxidant that plays an important role in many biological processes and is also an important medium analysis in various fields. In this work, a new electrochemical nanosensor capable of detecting and quantifying hydrogen peroxide was introduced. This nanosensor was fabricated by electrodepositing prussian blue (PB)/graphene quantum dots (GQDs)/polypyrrole (PPy) on single nanopore electrode etched from single gold nanoelectrode. This prepapred nanosensor exhibits good electrochemical response to hydrogen peroxide with high sensitivity and stability, with a linear response in the 2.0 and 80 µM by using amperometric method and differential pulse voltammetry (DPV) method. The limit of detections are 0.33 µM (S/N = 3) for amperometric method and 0.67 µM (S/N = 3) for differential pulse voltammetry (DPV) method, respectively. This nanosensor can be used for the determination of hydrogen peroxide in human urine, and can serve as a new electrochemical platform to monitor H2O2 release from single living cells due to its small overal dimension and high sensitivity.

Bulk anda single-cell transcriptome profiling reveals the molecular characteristics of T cell-mediated tumor killing in pancreatic cancer.

Background: Despite the potential of immune checkpoint blockade (ICB) as a promising treatment for Pancreatic adenocarcinoma (PAAD), there is still a need to identify specific subgroups of PAAD patients who may benefit more from ICB. T cell-mediated tumor killing (TTK) is the primary concept behind ICB. We explored subtypes according to genes correlated with the sensitivity to TKK and unraveled their underlying associations for PAAD immunotherapies. Methods: Genes that control the responsiveness of T cell-induced tumor destruction (GSTTK) were examined in PAAD, focusing on their varying expression levels and association with survival results. Moreover, samples with PAAD were separated into two subsets using unsupervised clustering based on GSTTK. Variability was evident in the tumor immune microenvironment, genetic mutation, and response to immunotherapy among different groups. In the end, we developed TRGscore, an innovative scoring system, and investigated its clinical and predictive significance in determining sensitivity to immunotherapy. Results: Patients with PAAD were categorized into 2 clusters based on the expression of 52 GSTTKs, which showed varying levels and prognostic relevance, revealing unique TTK patterns. Survival outcome, immune cell infiltration, immunotherapy responses, and functional enrichment are also distinguished among the two clusters. Moreover, we found the CATSPER1 gene promotes the progression of PAAD through experiments. In addition, the TRGscore effectively predicted the responses to chemotherapeutics or immunotherapy in patients with PAAD and overall survival. Conclusions: TTK exerted a vital influence on the tumor immune environment in PAAD. A greater understanding of TIME characteristics was gained through the evaluation of the variations in TTK modes across different tumor types. It highlights variations in the performance of T cells in PAAD and provides direction for improved treatment approaches.

Association of the triglyceride-glucose index with severity of coronary stenosis and in-hospital mortality in patients with acute ST elevation myocardial infarction after percutaneous coronary intervention: a multicentre retrospective analysis cohort study.

OBJECTIVES: To explore the impact of the triglyceride-glucose (TyG) index on the severity of coronary stenosis and the risk of in-hospital mortality in patients with acute ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). DESIGN: A multicentre retrospective cohort study. SETTING: Patients with STEMI undergoing PCI from three centres in China from 2015 to 2019. PARTICIPANTS: A total of 1491 individuals presenting with STEMI were enrolled. PRIMARY OUTCOME MEASURE: The degree of coronary stenosis was quantified by the Gensini score (GS). The association between the TyG index and the severity of coronary stenosis was explored by using a logistic regression analysis. Cox proportional hazards regression analyses were used to investigate the associations between the variables and in-hospital mortality. RESULTS: We found a significant correlation between the TyG index and the degree of coronary stenosis in the present study. The TyG index was an independent risk factor for the severity of coronary stenosis (OR 2.003, p<0.001). Using the lowest tertile of the TyG (T1) group as a reference, the adjusted ORs for the T2 group and the T3 group and a high GS were 1.732 (p<0.001), 1.968 (p<0.001), respectively, and all p for trend <0.001. For predicting a high GS, the TyG index's area under the curve was 0.668 (95% CI 0.635 to 0.700, p<0.001). Additionally, the TyG index was further demonstrated to be an independent predictor of in-hospital mortality in patients with STEMI (HR 1.525, p<0.001). CONCLUSIONS: The TyG index was associated with the severity of coronary stenosis and all-cause in-hospital mortality in patients with STEMI, which may help physicians precisely risk-stratify patients and implement individualised treatment.

A Cu-Ag double-layer coating strategy for stable and reversible Zn metal anodes.

Structuring a stable artificial coating to mitigate dendrite growth and side reactions is an effective strategy for protecting the Zn metal anode. Herein, a Cu-Ag double-layer metal coating is constructed on the Zn anode (Zn@Cu-Ag) by simple and in-situ displacement reactions. The Cu layer enhances the bond between the Ag layer and Zn substrate by acting as an intermediary, preventing the Ag coating from detachment. Concurrently, the Ag layer serves to improve the corrosion resistance of Cu metal. During plating, the initial Cu sheets and Ag particles on the surface of Zn@Cu-Ag electrode gradually transform into a flat and smooth layer, resulting in the formation of AgZn, AgZn3, and (Ag, Cu)Zn4 alloys. Alloys play a multifunctional role in inhibiting dendrite growth and side reactions due to decreased resistance, low nucleation barrier, enhanced zincophilicity, and strong corrosion resistance. Consequently, the Zn@Cu-Ag symmetric cell exhibits continuous stable performance for 3750 h at 1 mA cm-2. Furthermore, the Zn@Cu-Ag||Zn3V3O8 full cell achieves an initial capacity of 293.4 mAh g-1 and realizes long cycling stability over 1200 cycles. This work provides new insight into the engineering of an efficient artificial interface for highly stable and reversible Zn metal anodes.

Baicalin Maintains Articular Cartilage Homeostasis and Alleviates Osteoarthritis by Activating FOXO1.

Baicalin has been acknowledged for its anti-inflammatory properties. However, its potential impact on osteoarthritis (OA) has not yet been explored. Therefore, our study aimed to examine the effects of Baicalin on OA, both in laboratory and animal models. To evaluate its efficacy, human chondrocytes affected by OA were treated with interleukin-1ß and/or Baicalin. The effects were then assessed through viability tests using the cell counting kit-8 (CCK-8) method and flow cytometry. In addition, we analyzed the expressions of various factors such as FOXO1, autophagy, apoptosis, and cartilage synthesis and breakdown to corroborate the effects of Baicalin. We also assessed the severity of OA through analysis of tissue samples. Our findings demonstrate that Baicalin effectively suppresses inflammatory cytokines and MMP-13 levels caused by collagenase-induced osteoarthritis, while simultaneously preserving the levels of Aggrecan and Col2. Furthermore, Baicalin has been shown to enhance autophagy. Through the use of FOXO1 inhibitors, lentivirus-mediated knockdown, and chromatin immunoprecipitation, we verified that Baicalin exerts its protective effects by activating FOXO1, which binds to the Beclin-1 promoter, thereby promoting autophagy. In conclusion, our results show that Baicalin has potential as a therapeutic agent for treating OA (Clinical Trial Registration number: 2023-61).

Synthesis and evaluation of febrifugine derivatives as anticoccidial agents.

A series of new febrifugine derivatives with a 4(3H)-quinazolinone scaffold were synthesized and evaluated for their anticoccidial activity both in vitro and in vivo. The targets' in vitro activity against Eimeria tenella was studied using quantitative real-time reverse transcription polymerase chain reaction and Madin-Darby bovine kidney cells. Most of these compounds demonstrated anticoccidial efficacy, with inhibition ratios ranging from 3.3% to 85.7%. Specifically, compounds 33 and 34 showed significant inhibitory effects on the proliferation of E. tenella and exhibited lower cytotoxicity compared to febrifugine. The IC50 values of compounds 33 and 34 were 3.48 and 1.79 µM, respectively, while the CC50 values were >100 µM for both compounds. Furthermore, in a study involving 14-day-old chickens infected with 5 × 104 sporulated oocysts, treatment with five selected compounds (22, 24, 28, 33, and 34), which exhibited in vitro inhibition rate of over 50% at 100 µM, at a dose of 40 mg/kg in daily feed for 8 consecutive days showed that compound 34 possessed moderate in vivo activity against coccidiosis, with an anticoccidial index of 164. Structure-activity relationship studies suggested that spirocyclic piperidine may be a preferable substructure to maintain high effectiveness in inhibiting Eimeria spp., when the side chain 1-(3-hydroxypiperidin-2-yl)propan-2-one was replaced.

Qihuang Zhuyu formula alleviates coronary microthrombosis by inhibiting PI3K/Akt/αIIbß3-mediated platelet activation.

BACKGROUND: Coronary microembolism (CME) is commonly seen in the peri-procedural period of Percutaneous Coronary Intervention (PCI), where local platelet activation and endothelial cell inflammation crosstalk may lead to micro thrombus erosion and rupture, with serious consequences. Qihuang Zhuyu Formula (QHZYF) is a Chinese herbal compound with high efficacy against coronary artery disease, but its antiplatelet mechanism is unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of QHZYF on sodium laurate-induced CME using network pharmacology and in vitro and in vivo experiments. METHODS: We employed high-performance liquid chromatography mass spectrometry to identify the main components of QHZYF. Network pharmacology analysis, molecular docking and surface plasmon resonance (SPR) were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways mediating the effects of QHZYF on platelet activation. Next, we pretreated a sodium laurate-induced minimally invasive CME rat model with QHZYF. In vivo experiments were performed to examine cardiac function in rats, to locate coronary arteries on heart sections to observe internal microthrombi, to extract rat Platelet-rich plasma (PRP) for adhesion assays and CD62p and PAC-1 (ITGB3/ITGA2B) flow assays, and to measure platelet-associated protein expression in PRP. In vitro clot retraction and Co-culture of HUVECs with PRP were performed and the gene pathway was validated through flow cytometry and immunofluorescence. RESULTS: Combining UPLC-Q-TOF/MS technology and database mining, 78 compounds were finally screened as the putative and representative compounds of QHZYF, with 75 crossover genes associated with CME. QHZYF prevents CME mainly by regulating key pathways of the inflammation and platelets, including Lipid and atherosclerosis, Fluid shear stress, platelet activation, and PI3K-Akt signaling pathways. Five molecules including Calyson, Oroxin A, Protosappanin A,Kaempferol and Geniposide were screened and subjected to molecular docking and SPR validation in combination with Lipinski rules (Rule of 5, Ro5). In vivo experiments showed that QHZYF not only improved myocardial injury but also inhibited formation of coronary microthrombi. QHZYF inhibited platelet activation by downregulating expression of CD62p receptor and platelet membrane protein αIIbß3 and reduced the release of von Willebrand Factor (vWF), Ca2+ particles and inflammatory factor IL-6. Further analysis revealed that QHZYF inhibited the activation of integrin αIIbß3, via modulating the PI3K/Akt pathways. In in vitro experiments, QHZYF independently inhibited platelet clot retraction. Upon LPS induction, the activation of platelet membrane protein ITGB3 was inhibited via the PI3K/Akt pathway, revealing an important mechanism for attenuating coronary microthrombosis. We performed mechanistic validation using PI3K inhibitor LY294002 and Akt inhibitor MK-2206 to show that QHZYF inhibited platelet membrane protein activation and inflammation to improved coronary microvessel embolism by regulating PI3K/Akt/αIIbß3 pathways, mainly by inhibiting PI3K and Akt phosphorylation. CONCLUSION: QHZYF interferes with coronary microthrombosis through inhibition of platelet adhesion, activation and inflammatory crosstalk, thus has potential in clinical anti-platelet applications. Calyson, Oroxin A, Protosappanin A, Kaempferol and Geniposide may be the major active ingredient groups of QHZYF that alleviate coronary microthrombosis.

Baroreflex activation therapy for heart failure with reduced ejection fraction: A comprehensive systematic review and meta-analysis.

Background: In recent years, baroreflex activation therapy (BAT) has been utilized to treat heart failure with reduced ejection fraction (HFrEF). However, the supporting literature on its efficacy and safety is still limited. This investigation elucidates the effects of BAT in HFrEF patients to provide a reference for future clinical applications. Methods: This investigation follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Relevant investigations on the use of BAT in HFrEF patients were searched and selected from 5 databases, including Web of Science, MEDLINE, PubMed, Embase, and Cochrane Library, from inception to December 2022. The methodological quality of eligible articles was assessed via the Cochrane risk of bias tool, and for meta-analysis, RevMan (5.3) was used. Results: Randomized controlled trials comprising 343 participants were selected for the meta-analysis, which revealed that in HFrEF patients, BAT enhanced the levels of LVEF (MD: 2.97, 95 % CI: 0.53 to 5.41), MLHFQ (MD: -14.81, 95 % CI: -19.57 to -10.06) and 6MWT (MD: 68.18, 95 % CI: 51.62 to 84.74), whereas reduced the levels of LVEDV (MD: -15.79, 95 % CI: -32.96 to 1.37) and DBP (MD: -2.43, 95 % CI: -4.18 to -0.68). Conclusion: It was concluded that BAT is an efficient treatment option for HFrEF patients. However, to validate this investigation, further randomized clinical trials with multiple centers and large sample sizes are needed.

Integrated bioinformatics and experiment revealed that cuproptosis is the potential common pathogenesis of three kinds of primary cardiomyopathy.

Cuproptosis is a recently reported new mode of programmed cell death which might be a potential co-pathogenesis of three kinds of primary cardiomyopathy. However, no investigation has reported a clear relevance between primary cardiomyopathy and cuproptosis. In this study, the differential cuproptosis-related genes (CRGs) shared by three kinds of primary cardiomyopathy were identified in training sets. As a result, four CRGs shared by three kinds of primary cardiomyopathy were acquired and they were mainly related to biological processes such as cell death and immuno-inflammatory response through differential analysis, correlation analysis, GSEA, GSVA and immune cell infiltration analysis. Then, three key CRGs (K-CRGs) with high diagnostic value were identified by LASSO regression. The results of nomogram, machine learning, ROC analysis, calibration curve and decision curve indicated that the K-CRGs exhibited outstanding performance in the diagnosis of three kinds of primary cardiomyopathy. After that, in each disease, two molecular subtypes clusters were distinguished. There were many differences between different clusters in the biological processes associated with cell death and immunoinflammation and K-CRGs had excellent molecular subtype identification efficacy. Eventually, results from validation datasets and in vitro experiments verified the role of K-CRGs in diagnosis of primary cardiomyopathy, identification of primary cardiomyopathic molecular subtypes and pathogenesis of cuproptosis. In conclusion, this study found that cuproptosis might be the potential common pathogenesis of three kinds of primary cardiomyopathy and K-CRGs might be promising biomarkers for the diagnosis and molecular subtypes identification of primary cardiomyopathy.

Resorbable Membranes for Guided Bone Regeneration: Critical Features, Potentials, and Limitations.

Lack of horizontal and vertical bone at the site of an implant can lead to significant clinical problems that need to be addressed before implant treatment can take place. Guided bone regeneration (GBR) is a commonly used surgical procedure that employs a barrier membrane to encourage the growth of new bone tissue in areas where bone has been lost due to injury or disease. It is a promising approach to achieve desired repair in bone tissue and is widely accepted and used in approximately 40% of patients with bone defects. In this Review, we provide a comprehensive examination of recent advances in resorbable membranes for GBR including natural materials such as chitosan, collagen, silk fibroin, along with synthetic materials such as polyglycolic acid (PGA), polycaprolactone (PCL), polyethylene glycol (PEG), and their copolymers. In addition, the properties of these materials including foreign body reaction, mechanical stability, antibacterial property, and growth factor delivery performance will be compared and discussed. Finally, future directions for resorbable membrane development and potential clinical applications will be highlighted.

Evaluation the role of cuproptosis-related genes in the pathogenesis, diagnosis and molecular subtypes identification of atherosclerosis.

Background: At present, the pathogenesis of atherosclerosis has not been fully elucidated, and the diagnosis and treatment face great challenges. Cuproptosis is a novel cell death pattern that might be involved in the development of atherosclerosis. However, no research has reported the correlation between cuproptosis and atherosclerosis. Methods: The differential cuproptosis-related genes (CRGs) between atherosclerosis group and control group (A-CRGs) were discovered via differential expression analysis. The correlation analysis, PPI network analysis, GO, KEGG and GSEA analysis were performed to investigate the function of A-CRGs. The differences of biological function between atherosclerosis group and control group were investigated via immune infiltration analysis and GSVA. The LASSO regression, nomogram and machine learning models were constructed to predict atherosclerosis risk. The atherosclerosis molecular subtypes clusters were discovered via unsupervised cluster analysis. Subsequently, we used the above research methods to analyze the differential CRGs between clusters (M-CRGs) and evaluate the molecular subtypes identification performance of M-CRGs. Finally, we verified the diagnostic value for atherosclerosis and role in cuproptosis of these CRGs through the validation set and in vitro experiments. Results: Five A-CRGs were identified and they were mainly related to the biological function of copper ion metabolism and immune inflammatory response. The diagnostic models and nomogram of atherosclerosis based on 5 A-CRGs indicated that these genes had well diagnostic value. A total of two molecular subtypes clusters were obtained in the atherosclerosis group. There were many differences in biological functions between these two molecular subtypes clusters, such as mitochondrial outer membrane permeabilization and primary immunodeficiency. In addition, 3 M-CRGs were identified in the 2 clusters. Machine learning models and nomogram constructed based on M-CRGs showed that these genes had well molecular subtypes identification efficacy. In the end, the results of in vitro experiment and validation set confirmed the diagnostic value for atherosclerosis and role in cuproptosis of these genes. Conclusion: The cuproptosis may be a potential pathogenesis of atherosclerosis and CRGs may be promising markers for the diagnosis and molecular subtypes identification of atherosclerosis.

Coupled processes of groundwater dynamics and land subsidence in the context of active human intervention, a case in Tianjin, China.

To address the crisis of water shortage in the North China Plain, the Chinese government implemented the South-to-North Water Transfer Project (SNWTP). In this context, Tianjin, one of the main beneficiaries of this project, has been relieved from water shortages and begun to implement Groundwater Management Plans (GMP) since 2018, which undoubtedly have a significant effect on the groundwater recovery. Meanwhile, this provides a good case for studying the coupled process of ground settlement and groundwater dynamics, especially the soil deformation pattern driven by groundwater level (GWL) rebound. To analyze these issues in detail, field well data was collected to depict groundwater flow field. Moreover, geodetic data was also collated, including leveling, GPS, and InSAR, so that a vertical deformation field with high spatiotemporal resolution could be generated. The results reveal that the GWL of the third confined aquifer which is the main exploitation layer in Tianjin recovered significantly since 2018 with a rate of 2.1 m/yr. The dynamic deformation patterns indicate that the area of land subsidence cones in Tianjin has reduced significantly, accompanied by a sharply declining subsidence rate (decreased from -32.2 mm/yr to -4.5 mm/yr.). Particularly, a significant poroelastic rebound has occurred in the Wuqing and Beichen districts since 2020. Furthermore, due to the delayed pore pressure dissipation in the aquitard, we find a time delay of 0.3-5.5 years between land subsidence and GWL time series, which is far less than that estimated by hydrogeological parameters, as the latter ignored the recharge and recovery capacity of the aquifer system. Finally, an evolution models in Tianjin was presented to illustrate interactive process among the deformation, pore pressure, and hydraulic head. In general, the SNWDP and the GMP has restored the pore pressure of aquifer, reduced the land subsidence, and alleviated the groundwater storage depletion of Tianjin.