Small Left Ventricle in Patients With Atrial Fibrillation Is Associated With Increased Cardiovascular Risk.

BACKGROUND: It is still unclear whether small left ventricle (LV) is an adverse structural prognostic feature in patients with atrial fibrillation (AF). OBJECTIVES: The purpose of this study was to evaluate the association between small LV and risk of cardiovascular events in AF population. METHODS: From the China-AF registry, 7,764 patients with AF were enrolled and divided into groups with normal, small, and large LV size based on left ventricular end-diastolic dimension (LVEDD) measurement per the American Society of Echocardiography references. Cox models were used to assess the association between LV size or LVEDD with composite cardiovascular events (cardiovascular death, ischemic stroke or systemic embolism, or major bleeding). RESULTS: There were 308 (4.0%) participants assessed with small LV who were older, with lower body mass and blood pressure, and fewer comorbidities, and 429 (5.5%) were identified with large LV. Compared with the normal LV group, small LV and large LV were significantly associated with higher incidence of composite cardiovascular events (adjusted HR [aHR]: 1.54 [95% CI: 1.07-2.20] for small LV; aHR: 1.36 [95% CI: 1.02-1.81] for large LV) and cardiovascular death (aHR: 1.94 [95% CI: 1.14-3.28] for small LV; aHR: 1.83 [95% CI: 1.24-2.69] for large LV). Small LV was also associated with increased risk of major bleeding [aHR: 2.21 [95% CI: 1.01-4.86]). A U-shaped relationship between LVEDD and composite cardiovascular events was identified (Pnonlinear < 0.001). CONCLUSIONS: In a prospective AF cohort, small LV was independently associated with an increased risk of cardiovascular events, which needed consideration in risk stratification and management for patients with AF. (ChiCTR-OCH-13003729).

Characteristics of Right-Sided Accessory Pathways Associated With Right Cardiac Veins.

BACKGROUND: The anatomy of myocardial fibers around the right cardiac veins (RCVs) and their roles in accessory pathways (APs) are rarely reported. METHODS: Six RCV-APs were identified from 566 patients with right-sided APs. Mapping of retrograde atrial activation was performed using CARTO 3 system under orthodromic tachycardia or right ventricular pacing. Venography of RCVs was acquired at the earliest retrograde atrial activation. RESULTS: Patients enrolled had a median age of 30 (11-51) years, 5 of them were male. Venography of RCVs could be classified into 3 distinct patterns based on the identified ventricular branches, right marginal vein only (type I; n=3), both right marginal vein and anterior cardiac veins (type II; n=2), and anterior cardiac vein only (type III; n=1). Patients with type I venography had rS QRS pattern in lead V1, negative delta wave in lead III and negative or isoelectric delta wave in lead aVF. However, patients with type II and III venography had QS QRS patterns in lead V1 and variable patterns of delta wave in inferior leads. Earliest retrograde atrial activation was found at a median of 16.75 (14.60-20.00) mm away from the tricuspid annulus, all with A larger than V. At the earliest retrograde atrial activation, far-field ventricular electrogram was found 30 ms later than QRS onset in 1 patient under sinus rhythm. AP conduction was eliminated by mechanical pressure in 2 and by radiofrequency ablation in 4 at the ostium of the veins colocalizing with the earliest retrograde activation of the right atrium. No recurrence was observed during 36 (10-60) months follow-up. CONCLUSIONS: The RCV-AP is a rare form of right-sided APs characterized by atrial insertions distant from the annulus. ECG-speculated ventricular insertion sites conformed to the location of identified RCVs.

A Highly Conductive n-Type Conjugated Polymer Synthesized in Water.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a benchmark hole-transporting (p-type) polymer that finds applications in diverse electronic devices. Most of its success is due to its facile synthesis in water, exceptional processability from aqueous solutions, and outstanding electrical performance in ambient. Applications in fields like (opto-)electronics, bioelectronics, and energy harvesting/storage devices often necessitate the complementary use of both p-type and n-type (electron-transporting) materials. However, the availability of n-type materials amenable to water-based polymerization and processing remains limited. Herein, we present a novel synthesis method enabling direct polymerization in water, yielding a highly conductive, water-processable n-type conjugated polymer, namely, poly[(2,2'-(2,5-dihydroxy-1,4-phenylene)diacetic acid)-stat-3,7-dihydrobenzo[1,2-b:4,5-b']difuran-2,6-dione] (PDADF), with remarkable electrical conductivity as high as 66 S cm-1, ranking among the highest for n-type polymers processed using green solvents. The new n-type polymer PDADF also exhibits outstanding stability, maintaining 90% of its initial conductivity after 146 days of storage in air. Our synthetic approach, along with the novel polymer it yields, promises significant advancements for the sustainable development of organic electronic materials and devices.

Photocatalytic doping of organic semiconductors.

Chemical doping is an important approach to manipulating charge-carrier concentration and transport in organic semiconductors (OSCs)1-3 and ultimately enhances device performance4-7. However, conventional doping strategies often rely on the use of highly reactive (strong) dopants8-10, which are consumed during the doping process. Achieving efficient doping with weak and/or widely accessible dopants under mild conditions remains a considerable challenge. Here, we report a previously undescribed concept for the photocatalytic doping of OSCs that uses air as a weak oxidant (p-dopant) and operates at room temperature. This is a general approach that can be applied to various OSCs and photocatalysts, yielding electrical conductivities that exceed 3,000 S cm-1. We also demonstrate the successful photocatalytic reduction (n-doping) and simultaneous p-doping and n-doping of OSCs in which the organic salt used to maintain charge neutrality is the only chemical consumed. Our photocatalytic doping method offers great potential for advancing OSC doping and developing next-generation organic electronic devices.

Phenotypic and Immunological Characterization of Patients with Activated PI3Kδ Syndrome 1 Presenting with Autoimmunity.

PURPOSE: Autoimmunity is a significant feature of APDS1 patients. We aimed to explore the pathogenic immune phenotype and possible mechanisms of autoimmunity in APDS1 patients. METHODS: The clinical records and laboratory data of 42 APDS1 patients were reviewed. Immunophenotypes were evaluated by multiparametric flow cytometry. Autoantibodies were detected via antigen microarray analysis. RESULTS: A total of 42 children with PIK3CD gene mutations were enrolled. Immunological tests revealed increased proportions of effector memory cells (86%) and central memory cells (59%) among CD4+ T cells; increased proportions of effector memory cells (83%) and terminally differentiated effector memory T cells (38%) among CD8+ T cells. Fewer CD3+ T cells and B cells and higher IgG levels were reported in patients with autoimmunity. The proportion of Tregs was decreased, and the proportions of Th9, Tfh, and Tfr cells were increased in APDS1 patients. Among APDS1 patients, higher proportion of Th2 and Tfr cells were found in those with autoimmunity. The proportions of CD11c+ B and CD21lo B cells in patients with autoimmunity were significantly increased. Antigen microarray analysis revealed a wide range of IgG/IgM autoantibodies in patients with APDS1. In patients with autoimmunity, the proportion of Tfr might be positively correlated with autoantibodies. CONCLUSIONS: The pathogenic immune phenotype of APDS1 patients included (1) deceased CD3+ T-cell and B-cell counts and increased IgG levels in patients with autoimmunity, (2) an imbalanced T helper cell subset, (3) increased proportions of autoreactive B cells, and (4) distinct autoantibody reactivities in patients with autoimmunity.

Evaluation of an algorithm-guided photoplethysmography for atrial fibrillation burden using a smartwatch.

BACKGROUND: Wearable devices based on the PPG algorithm can detect atrial fibrillation (AF) effectively. However, further investigation of its application on long-term, continuous monitoring of AF burden is warranted. METHOD: The performance of a smartwatch with continuous photoplethysmography (PPG) and PPG-based algorithms for AF burden estimation was evaluated in a prospective study enrolling AF patients admitted to Beijing Anzhen Hospital for catheter ablation from September to November 2022. A continuous Electrocardiograph patch (ECG) was used as the reference device to validate algorithm performance for AF detection in 30-s intervals. RESULTS: A total of 578669 non-overlapping 30-s intervals for PPG and ECG each from 245 eligible patients were generated. An interval-level sensitivity of PPG was 96.3% (95% CI 96.2%-96.4%), and specificity was 99.5% (95% CI 99.5%-99.6%) for the estimation of AF burden. AF burden estimation by PPG was highly correlated with AF burden calculated by ECG via Pearson correlation coefficient (R2 = 0.996) with a mean difference of -0.59 (95% limits of agreement, -7.9% to 6.7%). The subgroup study showed the robust performance of the algorithm in different subgroups, including heart rate and different hours of the day. CONCLUSION: Our results showed the smartwatch with an algorithm-based PPG monitor has good accuracy and stability in continuously monitoring AF burden compared with ECG patch monitors, indicating its potential for diagnosing and managing AF.

Single-cell and Bulk RNA-Seq reveal angiogenic heterogeneity and microenvironmental features to evaluate prognosis and therapeutic response in lung adenocarcinoma.

Background: Angiogenesis stands as a pivotal hallmark in lung adenocarcinoma (LUAD), intricately shaping the tumor microenvironment (TME) and influencing LUAD progression. It emerges as a promising therapeutic target for LUAD, affecting patients' prognosis. However, its role in TME, LUAD prognosis, and its clinical applicability remain shrouded in mystery. Methods: We employed integrated single-cell and bulk transcriptome sequencing to unravel the heterogeneity of angiogenesis within LUAD cells. Through "consensus clustering", we delineated distinct angiogenic clusters and deciphered their TME features. "Monocle2" was used to unravel divergent trajectories within malignant cell subpopulations of LUAD. Additionally, regulon submodules and specific cellular communication patterns of cells in different angiogenic states were analyzed by "pyscenic" and "Cellchat" algorithms. The "univariate Cox" and "LASSO" algorithms were applied to build angiogenic prognostic models. Immunohistochemistry (IHC) on clinical samples validated the role of model factors in LUAD angiogenesis. We utilized CTRP 2.0 and PRISM databases for pinpointing sensitive drugs against lung adenocarcinoma. Results: Two clusters for the activation of angiogenesis were identified, with Cluster 1 showing a poor prognosis and a pro-cancerous TME. Three differentiated states of malignant epithelial LUAD cells were identified, which had different degrees of angiogenic activation, were regulated by three different regulon submodules, and had completely different crosstalk from other cells in TME. The experiments validate that SLC2A1 promotes angiogenesis in LUAD. ARS (Angiogenesis related score) had a high prognostic value; low ARSs showed immunotherapy benefits, whereas high ARSs were sensitive to 15 chemotherapeutic agents. Conclusion: The assessment of angiogenic clusters helps to determine the prognostic and TME characteristics of LUAD. Angiogenic prognostic models can be used to assess the prognosis, immunotherapeutic response, and chemotherapeutic drug sensitivity of LUAD.

Recent advances in functionalized ferrite nanoparticles: From fundamentals to magnetic hyperthermia cancer therapy.

Cancers are fatal diseases that lead to most death of human beings, which urgently require effective treatments methods. Hyperthermia therapy employs magnetic nanoparticles (MNPs) as heating medium under external alternating magnetic field. Among various MNPs, ferrite nanoparticles (FNPs) have gained significant attention for hyperthermia therapy due to their exceptional magnetic properties, high stability, favorable biological compatibility, and low toxicity. The utilization of FNPs holds immense potential for enhancing the effectiveness of hyperthermia therapy. The main hurdle for hyperthermia treatment includes optimizing the heat generation capacity of FNPs and controlling the local temperature of tumor region. This review aims to comprehensively evaluate the magnetic hyperthermia treatment (MHT) of FNPs, which is accomplished by elucidating the underlying mechanism of heat generation and identifying influential factors. Based upon fundamental understanding of hyperthermia of FNPs, valuable insights will be provided for developing efficient nanoplatforms with enhanced accuracy and magnetothermal properties. Additionally, we will also survey current research focuses on modulating FNPs' properties, external conditions for MHT, novel technical methods, and recent clinical findings. Finally, current challenges in MHT with FNPs will be discussed while prospecting future directions.

Ground-state electron transfer in all-polymer donor:acceptor blends enables aqueous processing of water-insoluble conjugated polymers.

Water-based conductive inks are vital for the sustainable manufacturing and widespread adoption of organic electronic devices. Traditional methods to produce waterborne conductive polymers involve modifying their backbone with hydrophilic side chains or using surfactants to form and stabilize aqueous nanoparticle dispersions. However, these chemical approaches are not always feasible and can lead to poor material/device performance. Here, we demonstrate that ground-state electron transfer (GSET) between donor and acceptor polymers allows the processing of water-insoluble polymers from water. This approach enables macromolecular charge-transfer salts with 10,000× higher electrical conductivities than pristine polymers, low work function, and excellent thermal/solvent stability. These waterborne conductive films have technological implications for realizing high-performance organic solar cells, with efficiency and stability superior to conventional metal oxide electron transport layers, and organic electrochemical neurons with biorealistic firing frequency. Our findings demonstrate that GSET offers a promising avenue to develop water-based conductive inks for various applications in organic electronics.

Thermoelectric coupling effect in BNT-BZT-xGaN pyroelectric ceramics for low-grade temperature-driven energy harvesting.

Pyroelectric energy harvesting has received increasing attention due to its ability to convert low-grade waste heat into electricity. However, the low output energy density driven by low-grade temperature limits its practical applications. Here, we show a high-performance hybrid BNT-BZT-xGaN thermal energy harvesting system with environmentally friendly lead-free BNT-BZT pyroelectric matrix and high thermal conductivity GaN as dopant. The theoretical analysis of BNT-BZT and BNT-BZT-xGaN with x = 0.1 wt% suggests that the introduction of GaN facilitates the resonance vibration between Ga and Ti, O atoms, which not only contributes to the enhancement of the lattice heat conduction, but also improves the vibration of TiO6 octahedra, resulting in simultaneous improvement of thermal conductivity and pyroelectric coefficient. Therefore, a thermoelectric coupling enhanced energy harvesting density of 80 µJ cm-3 has been achieved in BNT-BZT-xGaN ceramics with x = 0.1 wt% driven by a temperature variation of 2 oC, at the optical load resistance of 600 MΩ.

Intracellular Fusobacterium nucleatum infection attenuates antitumor immunity in esophageal squamous cell carcinoma.

Currently, the influence of the tumor microbiome on the effectiveness of immunotherapy remains largely unknown. Intratumoural Fusobacterium nucleatum (Fn) functions as an oncogenic bacterium and can promote tumor progression in esophageal squamous cell carcinoma (ESCC). Our previous study revealed that Fn is a facultative intracellular bacterium and that its virulence factor Fn-Dps facilitates the intracellular survival of Fn. In this study, we find that Fn DNA is enriched in the nonresponder (NR) group among ESCC patients receiving PD-1 inhibitor and that the serum antibody level of Fn is significantly higher in the NR group than in the responder (R) group. In addition, Fn infection has an opposite impact on the efficacy of αPD-L1 treatment in animals. Mechanistically, we confirm that Fn can inhibit the proliferation and cytokine secretion of T cells and that Fn-Dps binds to the PD-L1 gene promoter activating transcription factor-3 (ATF3) to transcriptionally upregulate PD-L1 expression. Our results suggest that it may be an important therapeutic strategy to eradicate intratumoral Fn infection before initiating ESCC immunotherapies.

Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients.

BACKGROUND: Lung adenocarcinoma (LUAD) is an extraordinarily malignant tumor, with rapidly increasing morbidity and poor prognosis. Immunotherapy has emerged as a hopeful therapeutic modality for lung adenocarcinoma. Furthermore, a prognostic model (based on immune genes) can fulfill the purpose of early diagnosis and accurate prognostic prediction. METHODS: Immune-related mRNAs (IRmRNAs) were utilized to construct a prognostic model that sorted patients into high- and low-risk groups. Then, the prediction efficacy of our model was evaluated using a nomogram. The differences in overall survival (OS), the tumor mutation landscape, and the tumor microenvironment were further explored between different risk groups. In addition, the immune genes comprising the prognostic model were subjected to single-cell RNA sequencing to investigate the expression of these immune genes in different cells. Finally, the functions of BIRC5 were validated through in vitro experiments. RESULTS: Patients in different risk groups exhibited sharply significant variations in OS, pathway activity, immune cell infiltration, mutation patterns, and immune response. Single-cell RNA sequencing revealed that the expression level of BIRC5 was significantly high in T cells. Cell experiments further revealed that BIRC5 knockdown markedly reduced LUAD cell proliferation. CONCLUSION: This model can function as an instrumental variable in the prognostic, molecular, and therapeutic prediction of LUAD, shedding new light on the optimal clinical practice guidelines for LUAD patients.

Intracellular Fusobacterium nucleatum infection increases METTL3-mediated m6A methylation to promote the metastasis of esophageal squamous cell carcinoma.

INTRODUCTION: The tumor-associated microbiota plays a vital role in cancer development. Accumulating evidence shows that Fusobacterium nucleatum (Fn) participates in the progression of multiple tumor types. However, the underlying mechanisms remain unclear. OBJECTIVES: This study examined the expression of methyltransferase-like protein 3 (METTL3) during Fn infection and elucidated the function and pathway of Fn-induced m6A methylation in esophageal squamous cell carcinoma (ESCC). METHODS: The abundance of Fn in patient tissues was determined by qPCR. Western blot, qRT-PCR, and immunohistochemistry were performed to measure METTL3 expression in cells and tissues. METTL3 function was evaluated in vitro by colony formation and cell migration assays. MeRIP-qPCR was performed to determine the relationship between METTL3 and c-Myc. In addition, the half-lives of genes that are downstream of METTL3 were determined with RNA stability assays. RESULTS: Fn was enriched in hepatocellular carcinoma (HCC), breast cancer (BRCA), ESCC, and colorectal cancer (CRC) tumor tissues. METTL3 expression was positively associated with Fn abundance in ESCC tissues. Fn could survive and proliferation as well as increase METTL3 expression in ESCC, HCC, CRC, and BRCA cells. Moreover, METTL3 overexpression promoted ESCC cells proliferation, migration in vivo and in vitro. Mechanistically, Intracellular Fn infection increases METTL3 transcription. METTL3 promoted c-Myc mRNA methylation in the 3'-untranslated Region (3'-UTR) and enhanced its mRNA stability in a YTH N6-Methyladenosine RNA binding protein 1(YTHDF1)-dependent manner, which contributes to Fn induced ESCC proliferation and metastasis. CONCLUSIONS: This study indicates that intracellular Fn infection promotes ESCC development and metastasis, and eradicating Fn infection may be a promising strategy for treating ESCC.

An ultrasensitive method for detecting mutations from short and rare cell-free DNA.

Circulating tumor DNA (ctDNA) was short and rare, making the detection performance of the current targeted sequencing methods unsatisfying. We developed the One-PrimER Amplification (OPERA) system and examined its performance in detecting mutations of low variant allelic frequency (VAF) in various samples with short-sized DNA fragments. In cell line-derived samples containing sonication-sheared DNA fragments with 50-150 bp, OPERA was capable of detecting mutations as low as 0.0025% VAF, while CAPP-Seq only detected mutations of >0.03% VAF. Both single nucleotide variant and insertion/deletion can be detected by OPERA. In synthetic fragments as short as 80 bp with low VAF (0.03%-0.1%), the detection sensitivity of OPERA was significantly higher compared to that of droplet digital polymerase chain reaction. The error rate was 5.9×10-5 errors per base after de-duplication in plasma samples collected from healthy volunteers. By suppressing "single-strand errors", the error rate can be further lowered by >5 folds in EGFR T790M hotspot. In plasma samples collected from lung cancer patients, OPERA detected mutations in 57.1% stage I patients with 100% specificity and achieved a sensitivity of 30.0% in patients with tumor volume of less than 1 cm3. OPERA can effectively detect mutations in rare and highly-fragmented DNA.

Nanomaterial Production from Metallic Vapor Bubble Collapse in Liquid Nitrogen.

Nanomaterials with unique structural and properties can be synthesized by rapid transition of the thermodynamic state. One promising method is through electrical explosion, which possesses ultrafast heating/quenching rates (dT/dt~109 K/s) of the exploding conductor. In this study, experiments were performed with fine metallic wire exploding in liquid nitrogen (liq N2, 77 K) under different applied voltages. For the first time in the literature, the physical image of the electrical explosion dynamics in liq N2 is depicted using electro-physical diagnostics and spatial-temporal-resolved photography. Specifically, the pulsation and collapse processes of the vapor bubble (explosion products) have been carefully observed and analyzed. As a comparison, an underwater electrical explosion was also performed. The experimental results suggest that the vapor bubble behavior in liq N2 differs from that in water, especially in the collapse phase, characterized by secondary small-scale bubbles in liq N2, but multiple bubble pulses in water; correspondingly, the products' characteristics are discrepant.

Identification of immune activation-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a major subtype of non-small cell lung cancer (NSCLC) with a highly heterogeneous tumor microenvironment. Immune checkpoint inhibitors (ICIs) are more effective in tumors with a pre-activated immune status. However, the potential of the immune activation-associated gene (IAG) signature for prognosis prediction and immunotherapy response assessment in LUAD has not been established. Therefore, it is critical to explore such gene signatures. Methods: RNA sequencing profiles and corresponding clinical parameters of LUAD were extracted from the TCGA and GEO databases. Unsupervised consistency clustering analysis based on immune activation-related genes was performed on the enrolled samples. Subsequently, prognostic models based on genes associated with prognosis were built using the last absolute shrinkage and selection operator (LASSO) method and univariate Cox regression. The expression levels of four immune activation related gene index (IARGI) related genes were validated in 12 pairs of LUAD tumor and normal tissue samples using qPCR. Using the ESTIMATE, TIMER, and ssGSEA algorithms, immune cell infiltration analysis was carried out for different groups, and the tumor immune dysfunction and rejection (TIDE) score was used to evaluate the effectiveness of immunotherapy. Results: Based on the expression patterns of IAGs, the TCGA LUAD cohort was classified into two clusters, with those in the IAG-high pattern demonstrating significantly better survival outcomes and immune cell infiltration compared to those in the IAG-low pattern. Then, we developed an IARGI model that effectively stratified patients into different risk groups, revealing differences in prognosis, mutation profiles, and immune cell infiltration within the tumor microenvironment between the high and low-risk groups. Notably, significant disparities in TIDE score between the two groups suggest that the low-risk group may exhibit better responses to ICIs therapy. The IARGI risk model was validated across multiple datasets and demonstrated exceptional performance in predicting overall survival in LUAD, and an IARGI-integrated nomogram was established as a quantitative tool for clinical practice. Conclusion: The IARGI can serve as valuable biomarkers for evaluating the tumor microenvironment and predicting the prognosis of LUAD patients. Furthermore, these genes probably provide valuable guidance for establishing effective immunotherapy regimens for LUAD patients.

Stable organic electrochemical neurons based on p-type and n-type ladder polymers.

Organic electrochemical transistors (OECTs) are a rapidly advancing technology that plays a crucial role in the development of next-generation bioelectronic devices. Recent advances in p-type/n-type organic mixed ionic-electronic conductors (OMIECs) have enabled power-efficient complementary OECT technologies for various applications, such as chemical/biological sensing, large-scale logic gates, and neuromorphic computing. However, ensuring long-term operational stability remains a significant challenge that hinders their widespread adoption. While p-type OMIECs are generally more stable than n-type OMIECs, they still face limitations, especially during prolonged operations. Here, we demonstrate that simple methylation of the pyrrole-benzothiazine-based (PBBT) ladder polymer backbone results in stable and high-performance p-type OECTs. The methylated PBBT (PBBT-Me) exhibits a 25-fold increase in OECT mobility and an impressive 36-fold increase in µC* (mobility × volumetric capacitance) compared to the non-methylated PBBT-H polymer. Combining the newly developed PBBT-Me with the ladder n-type poly(benzimidazobenzophenanthroline) (BBL), we developed complementary inverters with a record-high DC gain of 194 V V-1 and excellent stability. These state-of-the-art complementary inverters were used to demonstrate leaky integrate-and-fire type organic electrochemical neurons (LIF-OECNs) capable of biologically relevant firing frequencies of about 2 Hz and of operating continuously for up to 6.5 h. This achievement represents a significant improvement over previous results and holds great potential for developing stable bioelectronic circuits capable of in-sensor computing.

HSF1 expression in tumor-associated macrophages promotes tumor cell proliferation and indicates poor prognosis in esophageal squamous cell carcinoma

Purpose Tumor-associated macrophages (TAMs), are crucial for the survival and development of tumor cells. Heat shock factor 1 (HSF1) is a potent, complex carcinogenesis modulator, and esophageal cancer (EC) patients have a bad prognosis when HSF1 is highly expressed. HSF1's clinical importance and biological role in TAMs are still unknown. Methods The HSF1 expression profile and patient survival information were analyzed from the TCGA database. The infiltration of different types of immune cells in EC was evaluated based on HSF1 gene expression by Sangerbox 3.0. Immunochemistry was employed to assess HSF1 protein expression in 134 individuals with esophageal squamous cell carcinoma (ESCC), proceeded by association with clinicopathological variables. The role of macrophage-driven HSF1 were observed using HSF1-knockdown THP1 cells. Results High level of HSF1 have a poorer prognosis in individuals with EC. The expressing level of HSF1 was positively related to infiltration of M2 macrophages (P < 0.05). The expression of HSF1 in macrophages was an independent factor for DFS (P = 0.002) and OS (P = 0.002) in ESCC cases. HSF1 was up-regulated in IL-4 stimulation THP1 cells in a time-dependent manner. Under the heat stimulation condition, THP1-derived macrophages were more sensitive than tumor cells. Compared to IL-4 induced-THP1 cells control, the HSF1 knockdown in THP1 cell inhibited the growth and proliferation of ESCC cells. Conclusions The up-regulation of HSF1 was more rapid and could affect the proliferation of tumor cells in IL4-induced macrophages. The expression of HSF1 in TAMs can also serve as a marker for ESCC prognosis (AU)

Systolic Blood Pressure Time in Target Range and Cognitive Outcomes: Insights From the SPRINT MIND Trial.

BACKGROUND: The prognostic value of systolic blood pressure (SBP) time in target range (TTR) on cognitive outcomes among adults with hypertension remains unclear. METHODS: We performed secondary analysis of SPRINT MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension), which compared intensive (<120 mm Hg) versus standard (<140 mm Hg) SBP intervention in hypertensive individuals. TTR was calculated from baseline to month 3 using 110 to 130 mm Hg and 120 to 140 mm Hg as target range for the intensive and standard groups, respectively. Cognitive outcomes included probable dementia, mild cognitive impairment, and the composite of probable dementia or mild cognitive impairment. Cox regression models were used to evaluate the relationship between SBP-TTR and cognitive outcomes. RESULTS: A total of 8298 patients were included. Participants with higher TTR were younger and less likely to be women or to have a history of cardiovascular disease. After adjustment of baseline demographics, medical history, and mean SBP, a 1-SD (31.5%) increase in TTR was independently associated with a 14% lower risk of probable dementia (hazard ratio, 0.86 [95% CI, 0.76-0.98]; P=0.023). Sensitivity analysis showed consistent results when combining target range as 110 to 140 mm Hg. However, there was no significant association between SBP-TTR and mild cognitive impairment. CONCLUSIONS: In this post hoc analysis of SPRINT MIND, SBP-TTR was an independent predictor of probable dementia beyond mean SBP. Maintaining SBP within 110 to 140 mm Hg over time may be beneficial for dementia prevention. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.

[Surface modification of multifunctional ferrite magnetic nanoparticles and progress in biomedicine].

Magnetic ferrite nanoparticles (MFNPs) have great application potential in biomedical fields such as magnetic resonance imaging, targeted drugs, magnetothermal therapy and gene delivery. MFNPs can migrate under the action of a magnetic field and target specific cells or tissues. However, to apply MFNPs to organisms, further modifications on the surface of MFNPs are required. In this paper, the common modification methods of MFNPs are reviewed, their applications in medical fields such as bioimaging, medical detection, and biotherapy are summarized, and the future application directions of MFNPs are further prospected.