Expression of CDK9 in Newly Diagnosed Patients with Acute Myeloid Leukemia and its Clinical Significance.

BACKGROUND: This study investigated the role of cyclin-dependent kinase 9 (CDK9) expression levels and prognosis in acute myeloid leukemia (AML) by examining its expression at the time of initial diagnosis. METHODS: Bone marrow samples from 60 AML patients were collected for the observation group, with 20 normal human bone marrow samples serving as controls. Clinical and pathological data were gathered from the AML pa-tients. Real-time quantitative PCR (RT-qPCR) was employed to measure CDK9 expression levels in both groups, and the association between CDK9 expression, clinical characteristics, and prognosis in AML patients was analyzed. Kaplan-Meier curves were used to assess the impact of CDK9 on overall survival (OS) in AML, while Cox regression analysis was performed to identify prognostic factors in AML patients. RESULTS: The expression of CDK9 was significantly elevated in AML patients, compared to the control group (p < 0.05). High CDK9 expression was associated with increased white blood cell (WBC) count, poor treatment response, and worse prognosis compared to low expression (p < 0.05). Additionally, patients with high CDK9 expression exhibited significantly shortened OS compared to those with low expression (p < 0.05). High CDK9 expression emerged as an independent risk factor influencing prognosis in AML. CONCLUSIONS: CDK9 is markedly upregulated in AML patients, suggesting its potential utility as both a prognostic indicator and a therapeutic target, particularly for patients with unfavorable clinical and pathological characteristics and poor prognosis.

Li-Ga Alloy-Contained Hybrid Solid Electrolyte Interphase Induced by In Situ Polymerization for High-Performance Lithium Metal Batteries.

Construction of quasi-solid-state lithium metal batteries (LMBs) by in situ polymerization is considered a key strategy for the next generation of energy storage systems with high specific energy and safety. Poly(1,3-dioxolane) (PDOL)-based electrolytes have attracted wide attention among researchers, benefiting from the low cost and high ionic conductivity. However, interfacial deterioration and uncontrollable growth of lithium dendrites easily appeared in LMBs due to the high reactivity of lithium metal, resulting in the failure of LMBs. In this work, a strategy is developed of using Ga(OTF)3 as the initiator to obtain a PDOL-based gel electrolyte (GaPD). In addition, a hybrid stable solid electrolyte interphase (SEI) of lithium fluoride/Li2O/Li-Ga alloys is observed on the surface of lithium metal. Combined with density functional theory calculations, the hybrid SEI shows high affinity toward Li+, indicating that a uniform deposition of Li+ could be achieved. Therefore, the Li/GaPD/Li cell operates stably for 1600 h at room temperature. In addition, the LiFePO4/GaPD/Li cell retains a capacity retention rate of 90.2% over 200 cycles at 1 C. This work provides a reference for the practical application of in situ polymerization technology in high-performance and safe LMBs.

Roller-like Spore Carbon Sphere-Orientated Graphene Fibers Prepared via Rheological Engineering for Lithium Sulfur Batteries.

Flexible batteries with large energy densities, lightweight nature, and high mechanical strength are considered as an eager goal for portable electronics. Herein, we first propose free-standing graphene fiber electrodes containing roller-like orientated spore carbon spheres via rheological engineering. With the help of the orientated microfluidic cospinning technology and the plasma reduction method, spore carbon spheres are self-assembled and orientedly dispersed into numerous graphene flakes, forming graphene fiber electrodes enriched with internal rolling woven structures, which cannot only enhance the electrical contact between active materials but also effectively improve the mechanical strength and structure stability of graphene fiber electrodes. When the designed graphene fibers are combined with the active sulfur cathode and lithium metal anode, the assembled flexible lithium sulfur batteries possess superior electrochemical performance with high capacity (>1000 mA h g-1) and excellent cycling life as well as good mechanical properties. According to density functional theory and COMSOL simulations, the roller-like spore carbon sphere-orientated graphene fiber hosts provide reinforced trapping-catalytic-conversion behavior to soluble polysulfides and nucleation active sites to lithium metal, thus synergistically suppressing the shuttle effect of polysulfides at the cathode side and lithium dendrite growth at the anode side, thereby boosting the whole electrochemical properties of lithium sulfur batteries.

Antibacterial periodontal ligament stem cells enhance periodontal regeneration and regulate the oral microbiome.

BACKGROUND: The transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration. METHODS: We isolated human PDLSCs from periodontal ligament of extracted teeth. Rats' periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro. RESULTS: Microbiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37. CONCLUSIONS: Our findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health.

Unveiling the potential of MOF-based single-atom photocatalysts for the production of clean fuel and valuable chemical.

Harnessing solar energy through photocatalysis has excellent potential for powering sustainable chemical production, supporting the United Nations' environmental goals. Single-atoms (SAs) dispersed on catalyst surfaces are gaining attention for their highly active and durable nature. Metal-organic frameworks (MOFs) can provide enough reactive sites to sustain selectivity and durability over time because of their tunable channels and functional groups. Owing to their organized structures, MOFs are ideal platforms for securing individual atoms and promoting solar-driven reactions. Few reviews have, however, reflected the possibility of combining MOFs and SAs to produce potent photocatalysts that may produce clean fuels and valuable chemicals. This review provides a general overview of methods for combining MOFs and SAs to generate photocatalysts. The challenges associated with these MOF-based single-atom systems are also critically examined. Their future development is discussed as continued refinement helps to more fully leverage their advantages for boosting photocatalytic performances - turning sunlight into chemicals in a manner that supports sustainable development. Insights gained here could illuminate pathways toward realizing the profound potential of MOF-based single-atom photocatalysts to empower production driven by renewable solar energy.

Effects of a Novel Magnetic Nanomaterial on Oral Biofilms.

Dental caries is one of the most common oral chronic infectious diseases, and novel antibacterial materials must be developed to control plaque and inhibit formation of dental caries. Combining magnetic nanomaterials with antibacterial agents to decrease the formation of bacterial biofilm has been a hot topic in the biomedical field. The present study developed a novel magnetic nanomaterial chemically combined with dimethylaminododecyl methacrylate (DMADDM) and initially investigated its inhibiting effects on biofilms by using traditional caries-related bacteria and saliva flora models. The novel magnetic nanomaterials successfully loaded DMADDM according to thermogravimetric analysis, Fourier transform infrared spectroscopy, x-ray diffraction, vibrating sample magnetometry, scanning electron microscopy, and transmission electron microscopy results. Further, the novel nanoparticle Fe3O4@SiO2@DMADDM with concentration of 8 mg/mL could effectively reduce Streptococcus mutans biofilm and decrease the production of lactic acid. The 16S rDNA sequencing revealed that Fe3O4@SiO2@DMADDM could depress the proportion of caries-related bacteria in saliva-derived biofilm, such as Streptococcus, Veillonella, and Neisseria. Therefore, Fe3O4@SiO2@DMADDM is a novel effective antibacterial magnetic nanomaterial and has clinical potential in plaque control and dental caries prevention.

Air pollution exposure, chemical compositions, and risk of expiratory airflow limitation in youth in Northeast China.

BACKGROUND: Expiratory airflow limitation (EAL) is closely associated with respiratory health in youth and adulthood. Owing to limited evidence, we aim to estimate the association between air pollutants, both individually and in combination, along with their chemical compositions, and the risk of EAL in youth based on data obtained from Northeast China Biobank. METHODS: Pulmonary function was evaluated using a medical-grade pulmonary function analyzer, with EAL defined as a forced expiratory flow in 1 s/ forced vital capacity ratio of < 0.8. Land use regression models were used to predict exposure to six air pollutants. Air pollution score (APS) for each participant was constructed as combined exposure. The chemical composition of particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) was determined using a validated machine-learning algorithm. Logistic regression models were employed to estimate effect sizes, and odds ratio (OR) and 95 % confidence intervals (CI) were calculated. RESULTS: In total, 905 EAL cases were identified among the 4301 participants, with a prevalence of 21.04 %. Each inter-quartile range increase in APS was associated with a 25 % higher risk of EAL (OR = 1.25, 95 % CI: 1.12, 1.39). Among the pollutants analyzed, PM2.5 exposure had the strongest association with the risk of EAL (OR = 1.33, 95 % CI: 1.18, 1.52). Out of the five chemical components, sulfate (SO2-4) (OR = 1.39, 95 % CI: 1.24, 1.57) and ammonium (NH+4) (OR = 1.39, 95 % CI: 1.23, 1.57) exhibited the strongest associations with the risk of EAL. CONCLUSIONS: Overall, combined effects of air pollution increased the risk of EAL in youth, with SO2-4 and NH+4 emerging as the predominant contributing chemical components in Northeast China.

Assessment of hyperacute cerebral ischemia using laser speckle contrast imaging.

Accurate diagnosis of cerebral ischemia severity is crucial for clinical decision-making. Laser speckle contrast imaging based cerebral blood flow imaging can help assess the severity of cerebral ischemia by monitoring changes in blood flow. In this study, we simulated hyperacute ischemia in rats, isolating arterial and venous flow-related signals from cortical vasculature. Pearson correlation was used to examine the correlation between damaged vessels. Granger causality analysis was utilized to investigate causality correlation in ischemic vessels. Resting state analysis revealed a negative Pearson correlation between regional arteries and veins. Following cerebral ischemia induction, a positive artery-vein correlation emerged, which vanished after blood flow reperfusion. Granger causality analysis demonstrating enhanced causality coefficients for middle artery-vein pairs during occlusion, with a stronger left-right arterial effect than that of right-left, which persisted after reperfusion. These processing approaches amplify the understanding of cerebral ischemic images, promising potential future diagnostic advancements.

Prognostic aging gene-based score for colorectal cancer: unveiling links to drug resistance, mutation burden, and personalized treatment strategies.

OBJECTIVE: Colorectal cancer (CRC) is characterized by high incidence and mortality rates worldwide. In this study, we present a novel aging-related gene-based risk scoring system (Aging score) as a predictive tool for CRC prognosis. METHOD: We identified prognostic aging-related genes using univariate Cox regression analysis, revealing key biological processes in CRC progression. We then constructed a robust prognostic model using LASSO and multivariate Cox regression analyses, including four critical genes: CAV1, FOXM1, MAD2L1, and WT1. RESULT: The Aging score demonstrated high prognostic performance across the training, testing, and entire TCGA-CRC datasets, proving its reliability. High-risk patients identified by the Aging score had significantly shorter overall survival times than low-risk patients, indicating its potential for patient stratification and personalized treatment. The Aging score remained an independent prognostic factor compared to age, gender, and tumor stage. Additionally, the score was linked to tumor mutation burden and microsatellite instability, indicators of immune checkpoint inhibitor response. High-risk patients also showed higher estimated IC50 values for common chemotherapeutic drugs, suggesting possible treatment resistance. CONCLUSION: Our findings highlight the Aging score's potential to enhance clinical decision-making and pave the way for personalized CRC management.

Nitrogen nutrition effects on δ13C of plant respired CO2 are mostly caused by concurrent changes in organic acid utilisation and remobilisation.

Nitrogen (N) nutrition impacts on primary carbon metabolism and can lead to changes in δ13C of respired CO2. However, uncertainty remains as to whether (1) the effect of N nutrition is observed in all species, (2) N source also impacts on respired CO2 in roots and (3) a metabolic model can be constructed to predict δ13C of respired CO2 under different N sources. Here, we carried out isotopic measurements of respired CO2 and various metabolites using two species (spinach, French bean) grown under different NH4 +:NO3 - ratios. Both species showed a similar pattern, with a progressive 13C-depletion in leaf-respired CO2 as the ammonium proportion increased, while δ13C in root-respired CO2 showed little change. Supervised multivariate analysis showed that δ13C of respired CO2 was mostly determined by organic acid (malate, citrate) metabolism, in both leaves and roots. We then took advantage of nonstationary, two-pool modelling that explained 73% of variance in δ13C in respired CO2. It demonstrates the critical role of the balance between the utilisation of respiratory intermediates and the remobilisation of stored organic acids, regardless of anaplerotic bicarbonate fixation by phosphoenolpyruvate carboxylase and the organ considered.

Stair Climbing, Genetic Predisposition, and the Risk of Hip/Knee Osteoarthritis.

BACKGROUND: Few studies have explored the association between stair climbing and osteoarthritis (OA) to determine whether the former is a protective or risk factor for the latter. This study prospectively evaluated the associations among stair climbing, genetic susceptibility, and their interaction with the risk of incident hip/knee OA. METHODS: The cohort analyses included 398,939 participants from the UK Biobank. Stair climbing was assessed using a questionnaire. Genetic risk scores (GRSs) consisting of 70, 83, and 87 single-nucleotide polymorphisms for hip, knee, and hip/knee OA were constructed. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations among stair climbing, genetic predisposition, and hip and/or knee OA risk. RESULTS: After 3,621,735 person-years of follow-up, 31,940 patients developed OA. Stair climbing was positively associated with incident hip/knee (P for trend<0.001) and knee (P for trend<0.0001) OA but not hip OA. After adjustments, compared with no stair climbing, climbing >150 steps/day was associated with a higher risk of hip/knee OA (HR, 1.08; 95% CI, 1.03-1.12) and knee OA (HR, 1.13; 95% CI, 1.06-1.20). Although no significant interaction between stair climbing and the GRS of OA risk was found, the above associations were only significant in participants with middle and high GRSs. CONCLUSION: A higher frequency of stair climbing was positively associated with the risk of knee OA but not hip OA, highlighting the importance of avoiding frequent stair climbing in preventing knee OA, especially in genetically predisposed individuals.

CircRAPGEF5 acts as a modulator of RAS/RAF/MEK/ERK signaling during colorectal carcinogenesis.

Mutations in oncogenes such as KRAS, NRAS and BRAF promote the growth and survival of tumors, while excessive RAS/RAF/MEK/ERK activation inhibits tumor growth. In this study we examined the precise regulatory machinery that maintains a moderate RAS/RAF/MEK/ERK pathway activation during CRC. Here, using bioinformatic analysis, transcriptomic profiling, gene silencing and cellular assays we discovered that a circular RNA, circRAPGEF5, is significantly upregulated in KRAS mutant colorectal cancer (CRC) cells. CircRAPGEF5 suppressed mutant and constitutively activated KRAS and the expression of the death receptor TNFRSF10A. Silencing of circRAPGEF5-induced RAS/RAF/MEK/ERK signaling hyperactivation and apoptosis in CRC cells suggesting that an upregulation of circRAPEF5 may suppress the expression of TNFRSF10A and aid CRC progression by preventing apoptosis, while the direct interactions between circRAPGEF5 and elements of the RAS/RAF/MEK/ERK pathway was not identified, which nevertheless can be the basis for future research. Moreover, EIF4A3, was observed to share a similar expression pattern with circRAPEF5 and demonstrated to be a major controller of circRAPGEF5 via the promotion of circRAPGEF5 circularization and its silencing reduced circRAPGEF5 levels. Taken together, our findings reveal a mechanism of accurate RAS/RAF/MEK/ERK signaling regulation during CRC progression maintained by upregulation of circRAPGEF5 which may be a plausible target for future clinical applications that seek to induce CRC cell apoptosis via the RAS/RAF/MEK/ERK signaling pathway.

Gene-metabolite linkage marks stored red blood cell quality.

Red blood cell (RBC) transfusion has long been the cornerstone of treatment for multiple diseases, but there is a knowledge gap between biological and genetic factors impacting RBC storage quality and transfusion efficacy. In this issue of Cell Metabolism, Nemkov et al. present a multiomics approach to identify gene-metabolite associations in fresh and stored RBCs. These findings provide potential strategies to mark the quality of stored RBCs and improve their storage and transfusion performance.

Enhanced reducing capacity of citric acid for lithium-ion battery recycling under microwave-assisted leaching.

The management and sustainable recycling of spent lithium-ion batteries (LIBs) holds critical importance from both economic and environmental standpoints. H2O2 and ascorbic acid are widely used inorganic and organic reductants in the hydrometallurgical process for battery recycling. In this study, citric acid, as a reductant, was found to have superior metal leaching efficiencies under microwave-assisted leaching than H2O2 and ascorbic acid. The enhanced performance was attributed not only to the inherent reducing property of citric acid but also to the chelation of citric acid with Cu and Fe, resulting in the formation of reductive radicals under microwave. The effect of acid type, H2SO4 concentration, citric acid concentration, solid-liquid (S/L) ratio, reaction time, and temperature were investigated. 99.5 % of Li, 99.7 % of Mn, 99.5 % of Co, and 99.3 % of Ni were leached from spent lithium nickel manganese cobalt oxides (NCM) battery black mass using 0.2 mol/L H2SO4 and 0.05 mol/L citric acid at 120 °C for 20 min with a fixed S/L ratio of 10 g/L in the microwave-assisted leaching process. Leaching kinetic results were best fitted with the Avrami model, suggesting that the microwave-assisted leaching process was controlled by diffusion. The leaching activation energies of Li, Mn, Co, and Ni were 30.11 kJ/mol, 27.48 kJ/mol, 21.32 kJ/mol, and 33.29 kJ/mol, respectively, providing additional evidence that supports the proposed diffusion-controlled microwave-assisted leaching mechanism. This method provided a green and efficient solution for spent LIBs recycling.

External circuit loading mode regulates anode biofilm electrochemistry and pollutants removal in microbial fuel cells.

This study investigated the effects of different external circuit loading mode on pollutants removal and power generation in microbial fuel cells (MFC). The results indicated that MFC exhibited distinct characteristics of higher maximum power density (Pmax) (named MFC-HP) and lower Pmax (named MFC-LP). And the capacitive properties of bioanodes may affect anodic electrochemistry. Reducing external load to align with the internal resistance increased Pmax of MFC-LP by 54.47 %, without no obvious effect on MFC-HP. However, intermittent external resistance loading (IER) mitigated the biotoxic effects of sulfamethoxazole (SMX) (a persistent organic pollutant) on chemical oxygen demand (COD) and NH4+-N removal and maintained high Pmax (424.33 mW/m2) in MFC-HP. Meanwhile, IER mode enriched electrochemically active bacteria (EAB) and environmental adaptive bacteria Advenella, which may reduce antibiotic resistance genes (ARGs) accumulation. This study suggested that the external circuit control can be effective means to regulate electrochemical characteristics and pollutants removal performance of MFC.

Associations between different coffee types, neurodegenerative diseases, and related mortality: findings from a large prospective cohort study.

BACKGROUND: Observational studies have suggested associations between amount of coffee consumption and decreased risk of neurodegenerative diseases. However, these studies do not consider differences among coffee types, including sweetened, unsweetened, caffeinated, and decaffeinated varieties. OBJECTIVES: This study aims to identify associations between the consumption of various coffee types (sugar-sweetened, artificially sweetened, unsweetened, caffeinated, and decaffeinated) and risks of Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD), along with related mortality. METHODS: This prospective study included 204,847 participants (44.7% males) from the UK Biobank. Cox proportional hazards models were used to assess the associations of coffee type with neurodegenerative outcome. On the basis of coffee consumption, participants were divided into 5 groups: non-coffee consumers, >0-1 cup/d, ≥1-2 cups/d, ≥2-3 cups/d, and ≥3 cups/d. RESULTS: Over a median follow-up of 9 y, the study documented 1696 cases of ADRD, 1093 cases of PD, and 419 neurodegenerative-related deaths. In the multivariate analysis, compared with non-coffee consumers, those with the highest intake of unsweetened and caffeinated coffee (≥3 cups/d) showed hazard ratios (95% confidence intervals) of 0.75 (0.62, 0.91) for ADRD, 0.71 (0.56, 0.91) for PD, and 0.67 (0.44, 1.01) for neurodegenerative-related death. However, no significant associations were noted in either decaffeinated or sugar/artificially sweetened coffee groups (P > 0.05). CONCLUSIONS: Higher intake of caffeinated coffee, particularly the unsweetened variety, was associated with reduced risks of ADRD and PD. No such associations were observed for sugar-sweetened or artificially sweetened coffee.

Savolitinib conferred sensitivity in a patient with D1228H mutation-induced capmatinib-resistant MET exon 14 skipping mutated lung adenocarcinoma.

Traditionally, the D1228 E/G/H/N mutation has been thought to cause Type I MET-TKI resistance. We reported a 75-year-old female with non-small cell lung cancer harboring MET exon 14 skipping mutation, who developed acquired MET D1228H mutation induced by capmatinib treatment. Interestingly, the patient demonstrated marked response to second-line savolitinib treatment with the duration of response of 19 months and several additional metastatic lesions appeared. Pathological assessment of rebiopsy sample showed adenocarcinoma and targeted next-generation sequencing revealed the loss of MET D1228H mutation and presence of MET p.Y1230N mutation. In response, the treatment regimen was amended to include a daily administration of 60 mg of cabozantinib, which resulted in moderate size reduction of the tumours. The switch of resistance mutations indicated that different type Ib MET inhibitors may exhibit distinct mechanisms of resistance. We call for futher studies on resistance based on patient-derived pre-clinical models including patient-derived tumor-like cell clusters, patient-derived organoids, and patient-derived xenografts.

Selective bronchial occlusion for acquired bronchobiliary fistula caused by treatment of hepatocellular carcinoma: A case series.

Acquired bronchobiliary fistula (ABBF) is very rare among the complications that occur in patients with hepatocellular carcinoma (HCC) after treatment. Although surgery and drainage have been the main methods for treating ABBF for a long time, they are not entirely suitable for patients with refractory ABBF resulting from HCC therapy. In this study, we present four cases of ABBF caused by HCC treatment, who were treated using selective bronchial occlusion (SBO). Among the 4 patients with ABBF treated with SBO, 3 cases successfully blocked ABBF with SBO, and the treatment success rate was 75%. All successfully treated patients reported disappearance of symptoms of bilioptysis and cough was alleviated. No life-threatening adverse reactions were reported following SBO intervention, and no deaths occurred. We believe that the use of video bronchoscopy to place a self-made silicone plug in the bronchus to treat refractory ABBF is a feasible palliative treatment, which can significantly improve the condition of ABBF patients.

Accelerometer-measured intensity-specific physical activity, genetic predisposition, and the risk of venous thromboembolism: A cohort study.

OBJECTIVES: The association between physical activity and venous thromboembolism (VTE) remains unclear. Therefore, we investigated the prospective dose-response associations between accelerometer-measured intensity-specific physical activity and new-onset VTE, accounting for genetic risk. METHODS: In total, 85,116 participants from the UK Biobank were included. Incident VTE was identified via linked hospital records and death registries. A weighted polygenic risk score (PRS) was used to quantifying genetic risk for VTE, with higher values indicating a high genetic risk. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the associations. RESULTS: Overall, 1,182 incident VTE cases were documented during a median follow-up of 6.18 years. In the overall study population, the participants in the highest quartiles of total volume of physical activity (0.60 [0.45, 0.79]), moderate-to-vigorous-intensity physical activity (0.66 [0.51, 0.86]), and light-intensity physical activity (0.66 [0.51, 0.85]) had lower adjusted HRs (95% CIs) for VTE than those of participants in the lowest quartiles. Both total volume of physical activity and light-intensity physical activity were negatively associated with VTE risk in participants with low, intermediate, and high PRS. However, moderate-to-vigorous-intensity physical activity was only protective against VTE in participants with low and intermediate PRS, with a significant interaction (P for interaction=0.02). CONCLUSION: Higher levels of physical activity of any intensity were associated with a lower risk of new-onset VTE. However, the negative association between moderate-to-vigorous-intensity physical activity and new-onset VTE was significant only in participants with low and intermediate genetic predispositions to VTE.

Based on the UK Biobank cohort of 85,116 participants, this study aimed to explore the longitudinal associations between accelerometer-measured intensity-specific physical activity (PA) and risk of venous thromboembolism (VTE) and whether these associations could be modified by genetic predisposition, as reflected by polygenic risk scores (PRS), with higher values indicating a higher genetic risk. Our results showed that the risk of new-onset VTE decreased with increasing PA until total volume of PA, moderate-to-vigorous-intensity PA, and light-intensity PA reached approximately 40 milligravity/day, 45 mins/day, and 350 mins/day, respectively, and then remained relatively constant. The VTE-PRS modified the association between moderate-to-vigorous-intensity PA and VTE risk. The protective association between moderate-to-vigorous-intensity PA and the risk of VTE was more pronounced among participants with the lowest level of VTE-PRS.

Infection-Sensitive SPION/PLGA Scaffolds Promote Periodontal Regeneration via Antibacterial Activity and Macrophage-Phenotype Modulation.

Inflammation caused by a bacterial infection and the subsequent dysregulation of the host immune-inflammatory response are detrimental to periodontal regeneration. Herein, we present an infection-sensitive scaffold prepared by layer-by-layer assembly of Feraheme-like superparamagnetic iron oxide nanoparticles (SPIONs) on the surface of a three-dimensional-printed polylactic-co-glycolic acid (PLGA) scaffold. The SPION/PLGA scaffold is magnetic, hydrophilic, and bacterial-adhesion resistant. As indicated by gene expression profiling and confirmed by quantitative real-time reverse transcription polymerase chain reaction and flow cytometry analysis, the SPION/PLGA scaffold facilitates macrophage polarization toward the regenerative M2 phenotype by upregulating IL-10, which is the molecular target of repair promotion, and inhibits macrophage polarization toward the proinflammatory M1 phenotype by downregulating NLRP3, which is the molecular target of anti-inflammation. As a result, macrophages modulated by the SPS promote osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) in vitro. In a rat periodontal defect model, the SPION/PLGA scaffold increased IL-10 secretion and decreased NLRP3 and IL-1ß secretion with Porphyromonas gingivalis infection, achieving superior periodontal regeneration than the PLGA scaffold alone. Therefore, this antibacterial SPION/PLGA scaffold has anti-inflammatory and bacterial antiadhesion properties to fight infection and promote periodontal regeneration by immunomodulation. These findings provide an important strategy for developing engineered scaffolds to treat periodontal defects.