Association between the insufficient improvement of the quantitative flow ratio and worsening outcomes in ST-segment elevated myocardial infarction: a multicentre prospective cohort study.

Background: Improved coronary physiological function after percutaneous coronary intervention (PCI) has been shown to improve prognosis in stable ischaemic heart disease, but has not yet been explored in ST-segment elevated myocardial infarction (STEMI). The study sought to determine whether an improvement in the quantitative flow ratio (QFR) could improve the prognosis of STEMI patients undergoing primary PCI. Methods: Patients diagnosed with STEMI who were receiving primary PCI were recruited for the study. Those with thrombolysis in myocardial infarction (TIMI) flow <2 after wiring were excluded. The ΔQFR was calculated using the following formula: ΔQFR = post-PCI QFR - pre-stent QFR. The primary endpoint was the composite event, including recurrent myocardial infarction (MI) and acute heart failure (AHF). Results: In total, 515 STEMI patients with a median follow-up of 364 days were enrolled in the study. Based on the cut-off value from the receiver operator characteristic (ROC) curve, the patients were divided into the following two groups: the lower ΔQFR group (≤0.25, N=332); and the normal ΔQFR group (>0.25, N=183). Patients with a lower ΔQFR had a relatively higher rate of MI/AHF (10.5% vs. 4.4%, P=0.019) and AHF (7.2% vs. 2.7%, P=0.044). A lower ΔQFR was significantly associated with a higher incidence of MI/AHF [hazard ratio (HR) =2.962, 95% confidence interval (CI): 1.358-6.459, P=0.006, respectively] after adjusting for potential confounders. Pre-stent angiographic microvascular resistance [odds ratio (OR) =1.027, 95% CI: 1.022-1.033, P<0.001] and the stent-to-vessel diameter ratio <1.13 (OR =1.766, 95% CI: 1.027-3.071, P=0.04) were independent predictors of a lower ΔQFR. Conclusions: An insufficient improvement in the QFR contributes to worsening outcomes and might be a useful tool for risk stratification in STEMI.

Phase Change Nanocapsules Enabling Dual-Mode Thermal Management for Fast-Charging Lithium-Ion Batteries.

The fast-charging performance of conventional lithium-ion batteries (LIBs) is determined by the working temperature. LIBs may fail to work under harsh conditions, especially in the low-temperature range of the local environment or in the high-temperature circumstances resulting from the release of substantial Joule heating in the short term. Constructing a thermal engineering framework for thermal regulation and maintaining the battery running at an appropriate temperature range are feasible strategies for developing temperature-tolerant, fast-charging LIBs. In this work, we prepare phase change nanocapsules as a thermal regulating layer on the cell surface. The polyurea shells of the nanocapsules are decorated with polyaniline, where the molecular vibration of polyaniline is enhanced under solar irradiation, enabling light-to-heat conversion that achieves an effective temperature increment at low temperatures. Based on the large latent heat storage capability of the n-octadecane core in the nanocapsules, the thermal regulating layer is sufficient to modulate strong heat release when operating LIBs at a high current rate, which efficiently prevents strong side reactions at high temperatures or even the occurrence of thermal runaway. This work highlights the promise of optimizing the operating temperature with a thermal regulator to ensure the safety and performance stability of fast-charging LIBs.

A high-performance chiral 19F-labeled probe with an increased structural twisting.

We developed a new strategy to enhance the chiral discrimination capability of 19F-labeled probes by tuning the torsion angle of the probe's backbone, allowing for the resolution of challenging analytes. Its versatility is demonstrated through the superior performance and the wide analyte scope.

Characterization of a wheat stable QTL for spike length and its genetic effects on yield-related traits.

Spike length (SL) is one of the most important agronomic traits affecting yield potential and stability in wheat. In this study, a major stable quantitative trait locus (QTL) for SL, i.e., qSl-2B, was detected in multiple environments in a recombinant inbred line (RIL) mapping population, KJ-RILs, derived from a cross between Kenong 9204 (KN9204) and Jing 411 (J411). The qSl-2B QTL was mapped to the 60.06-73.06 Mb region on chromosome 2B and could be identified in multiple mapping populations. An InDel molecular marker in the target region was developed based on a sequence analysis of the two parents. To further clarify the breeding use potential of qSl-2B, we analyzed its genetic effects and breeding selection effect using both the KJ-RIL population and a natural mapping population, which consisted of 316 breeding varieties/advanced lines. The results showed that the qSl-2B alleles from KN9204 showed inconsistent genetic effects on SL in the two mapping populations. Moreover, in the KJ-RILs population, the additive effects analysis of qSl-2B showed that additive effect was higher when both qSl-2D and qSl-5A harbor negative alleles under LN and HN. In China, a moderate selection utilization rate for qSl-2B was found in the Huanghuai winter wheat area and the selective utilization rate for qSl-2B continues to increase. The above findings provided a foundation for the genetic improvement of wheat SL in the future via molecular breeding strategies.

Evaluating public opinions: informing public health policy adaptations in China amid the COVID-19 pandemic.

Public concern regarding safety policies serious consequences is anticipated to persist over an extended duration. A study examining a case of rapid public health policy adaptation in China during the COVID-19 epidemic was conducted by gathering public opinion data from major social media platforms. A systematic approach to comprehend public opinion was developed. Five fundamental elements and four dimensions were delineated. An indicator system was established utilizing the K-means text clustering model. Public prediction, expectation, and their evolution underlying public concern were elucidated employing TF-IDF text mining models. The HMM elucidated the way public opinion influences policy adjustments. The findings underscore that public concern regarding enduring events undergoes temporal shifts, mirroring the evolution of public opinion towards policy. Public opinion aroused by both the original event and derived events collaboratively influence policy adjustments. In China, public opinion serves as a mechanism for policy feedback and oversight; notably, negative public sentiment plays a pivotal role in expediting policy transitions. These findings aid in refining policies to mitigate emergencies through a feedback loop, thereby averting the emergence of safety risks such as social unrest prompted by public opinion.

Quantitative trait loci detection for three tiller-related traits and the effects on wheat (Triticum aestivum L.) yields.

KEY MESSAGE: A total of 38 putative additive QTLs and 55 pairwise putative epistatic QTLs for tiller-related traits were reported, and the candidate genes underlying qMtn-KJ-5D, a novel major and stable QTL for maximum tiller number, were characterized. Tiller-related traits play an important role in determining the yield potential of wheat. Therefore, it is important to elucidate the genetic basis for tiller number when attempting to use genetic improvement as a tool for enhancing wheat yields. In this study, a quantitative trait locus (QTL) analysis of three tiller-related traits was performed on the recombinant inbred lines (RILs) of a mapping population, referred to as KJ-RILs, that was derived from a cross between the Kenong 9204 (KN9204) and Jing 411 (J411) lines. A total of 38 putative additive QTLs and 55 pairwise putative epistatic QTLs for spike number per plant (SNPP), maximum tiller number (MTN), and ear-bearing tiller rate (EBTR) were detected in eight different environments. Among these QTLs with additive effects, three major and stable QTLs were first documented herein. Almost all but two pairwise epistatic QTLs showed minor interaction effects accounting for no more than 3.0% of the phenotypic variance. The genetic effects of two colocated major and stable QTLs, i.e., qSnpp-KJ-5D.1 and qMtn-KJ-5D, for yield-related traits were characterized. The breeding selection effect of the beneficial allele for the two QTLs was characterized, and its genetic effects on yield-related traits were evaluated. The candidate genes underlying qMtn-KJ-5D were predicted based on multi-omics data, and TraesKN5D01HG00080 was identified as a likely candidate gene. Overall, our results will help elucidate the genetic architecture of tiller-related traits and can be used to develop novel wheat varieties with high yields.

Microplastics in three types of human arteries detected by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS).

Microplastics are ubiquitous in the environment. Human body can be exposed to microplastics through inhalation and ingestion and some microplastics can enter the blood and accumulate in various tissues and organs throughout the body. Animal experiments have suggested that microplastics may promote atherosclerosis. However, data on microplastics in human arteries and clinical evidence supporting a link between microplastics and atherosclerosis are currently lacking. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was used in this study to detect microplastics in three types of human arteries: coronary and carotid arteries with atherosclerotic plaques, as well as the aorta without plaques. Microplastics were detected in all 17 arterial samples, with an average concentration of 118.66 ± 53.87 µg/g tissue. Four types of microplastics were identified: polyethylene terephthalate (PET, 73.70%), polyamide-66 (PA-66, 15.54%), polyvinyl chloride (PVC, 9.69%), and polyethylene (PE, 1.07%). Most importantly, the concentration of microplastics in arteries containing atherosclerotic plaques, both coronary arteries (156.50 ± 42.14 vs. 76.26 ± 14.86 µg/g tissue, P = 0.039), and carotid arteries (133.37 ± 60.52 vs. 76.26 ± 14.86 µg/g tissue, P = 0.015), was significantly higher than that in aortas which did not contain atherosclerotic plaques, suggesting that microplastics might be associated with atherosclerosis in humans. This study provides valuable data for further hazard assessments of microplastics on human cardiovascular health.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk.

INTRODUCTION: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). RESULTS: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5-32) and 52.7 cm3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/ß = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). CONCLUSION: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.

Eriodictyol inhibits the motility, angiogenesis and tumor growth of hepatocellular carcinoma via NLRP3 inflammasome inactivation.

NLRP3 involves in the development of hepatocellular carcinoma (HCC). Eriodictyol has shown its inhibitory effect on HCC cell proliferation. However, the underlying mechanism of eriodictyol in HCC is still unclear. This study aimed to explore the effect of and mechanism of eriodictyol on HCC. In this study, compared with eriodictyol (0 µM) group, eriodictyol significantly suppressed HepG2 cells (eriodictyol of 25, 50 and 100 µM) and Huh-7 cells (eriodictyol of 50 and 100 µM) viability, invasion, tube formation, metastasis-related genes MMP3, MMP16 and angiogenesis regulator VEGFA expressions with IC50 of 45.63 µM and 78.26 µM in vitro, respectively. Besides, eriodictyol significantly repressed NLRP3 expression, and reduced the protein levels of NLRP3 inflammasome-related proteins, adapter protein ASC, caspase-1, interleukin (IL)-18, and IL-1ß in HepG2 (eriodictyol of 25, 50 and 100 µM) and Huh-7 cells (eriodictyol of 50 and 100 µM), respectively. Meanwhile, compared with control group, NLRP3 overexpression reversed the anti-metastatic effects of 100 µM eriodictyol on HCC cells invasion, tube formation, and metastasis-related genes MMP3, MMP16 and angiogenesis regulator VEGFA expressions, whereas NLRP3 knockdown enhanced the anti-metastatic effects of 100 µM eriodictyol on HCC cells. In vivo, compared with control group, eriodictyol significantly reduced the tumor growth, liver damage, inhibited the activation of NLRP3 inflammasome, and improved liver function, whereas NLRP3 overexpressing neutralized the anti-tumor effects of eriodictyol and degraded liver function. Hence, eriodictyol inhibited HCC cell viability, motility, angiogenesis and tumor growth via NLRP3 inflammasome inactivation both in vitro and in vivo.

A review of SERS coupled microfluidic platforms: From configurations to applications.

Microfluidic systems have attracted considerable attention due to their low reagent consumption, short analysis time, and ease of integration in comparison to conventional methods, but still suffer from shortcomings in sensitivity and selectivity. Surface enhanced Raman scattering (SERS) offers several advantages in the detection of compounds, including label-free detection at the single-molecule level, and the narrow Raman peak width for multiplexing. Combining microfluidics with SERS is a viable way to improve their detection sensitivity. Researchers have recently developed several SERS coupled microfluidic platforms with substantial potential for biomolecular detection, cellular and bacterial analysis, and hazardous substance detection. We review the current development of SERS coupled microfluidic platforms, illustrate their detection principles and construction, and summarize the latest applications in biology, environmental protection and food safety. In addition, we innovatively summarize the current status of SERS coupled multi-mode microfluidic platforms with other detection technologies. Finally, we discuss the challenges and countermeasures during the development of SERS coupled microfluidic platforms, as well as predict the future development trend of SERS coupled microfluidic platforms.

Ion Migration in Lead-Halide Perovskites: Cation Matters.

Metal halide perovskites exhibit remarkable properties for optoelectronic applications, yet their susceptibility to ion migration poses challenges for device stability. Previous research has predominantly focused on the migration of the halide ions. However, the migration of cations, which also has a significant influence on the device performance, is largely overlooked. In this Perspective, we review the migration of cations and their impacts on perovskite materials and devices. Special attention shall be devoted to recent insights into the migration of L-site organic cations in 2D/3D perovskites. We outline inspirations and directions for further research into the cation migration of perovskites, highlighting new possibilities in advancing perovskite optoelectronics.

Mesoscopic Model for Reversible Adsorption Stage of Albumin and Fibrinogen on TiO2 Surface.

The competitive behavior of proteins in the reversible adsorption stage plays a crucial role in determining the composition of the protein layer and the subsequent biological responses to the biomaterial. However, such competitive adsorption is a mesoscopic process at physiological protein concentration, and neither a macroscopic experiment nor microscopic MD (molecular dynamics) simulation is suitable to clarify it. Here, we proposed a mesoscopic DPD (dissipative particle dynamics) model to illustrate the competitive process of albumin and fibrinogen on TiO2 surface with its parameters deduced from our previous MD simulation, and proved the model well retained the diffusion and adsorption properties of proteins in the competitive adsorption on the plane surface. We then applied the model to the competitive adsorption on the surfaces with different nanostructures and observed that when the nanostructure size is much larger than that of protein, the increase in surface area is the main influencing factor; when the nanostructure size is close to that of protein, the coordination between the nanostructure and the size and shape of protein significantly affects the competitive adsorption process. The model has revealed many mechanical phenomena observed in previous experimental studies and has the potential to contribute to the development of high-performance biomaterials.

Association of indoor dampness indicators with rheumatic diseases/symptoms in older adults: A comparative cross-sectional study in Chongqing and Beijing.

Dampness is strongly associated with rheumatic diseases, which particularly affect the older adults. Tackling dampness is therefore important, especially given that climate change is expected to exacerbate rheumatic diseases; however, limited studies have compared the risk of rheumatic diseases in older adults based on humidity levels across different regions. To explore this, a comparative cross-sectional study was conducted to collect information on the residential characteristics, lifestyles, and health outcomes of 2000 individuals aged 60-74 years from Chongqing and Beijing. From this data, we tested for an association between six indoor dampness indicators and rheumatic related diseases/symptoms. The results showed that the risk values for joint pain were higher in Chongqing than in Beijing. Moreover, the risk of joint stiffness increased more strongly in Chongqing than in Beijing as the cumulative number of dampness exposure indicators increased. The key indoor dampness indicators affecting rheumatic diseases were different for Chongqing and Beijing. Overall, this study compared the risk of rheumatic diseases in older adults in the north and south of China because of dampness exposure and, from these, provided suggestions for modifying the indoor environments to prevent or reduce rheumatic symptoms.

Immunologic Crosstalk of Endoplasmic Reticulum Stress Signaling in Bladder Cancer.

Bladder cancer (BC) is a common malignant tumor of the urinary system. While current approaches involving adjuvant chemotherapy, radiotherapy, and immunotherapy have shown significant progress in BC treatment, challenges, such as recurrence and drug resistance, persist, especially in the case of muscle-invasive bladder cancer (MIBC). This is mainly due to the lack of pre-existing immune response cells in the tumor immune microenvironment. Micro-environmental changes (such as hypoxia and under-nutrition) can cause the aggregation of unfolded and misfolded proteins in the lumen, which induces endoplasmic reticulum (ER) stress. ER stress and its downstream signaling pathways are closely related to immunogenicity and tumor drug resistance. ER stress plays a pivotal role in a spectrum of processes within immune cells and the progression of BC cells, encompassing cell proliferation, autophagy, apoptosis, and resistance to therapies. Recent studies have increasingly recognized the potential of natural compounds to exhibit anti-BC properties through ER stress induction. Still, the efficacy of these natural compounds remains less than that of immune checkpoint inhibitors (ICIs). Currently, the ER stress-mediated immunogenic cell death (ICD) pathway is more encouraging, which can enhance ICI responses by mediating immune stemness. This article provides an overview of the recent developments in understanding how ER stress influences tumor immunity and its implications for BC. Targeting this pathway may soon emerge as a compelling therapeutic strategy for BC.

Optimized design of an enthesis-mimicking suture anchor-tendon hybrid graft for mechanically robust bone-tendon repair.

Repair of functionally graded biological interfaces requires joining dissimilar materials such as hard bone to soft tendon/ligament, with re-injuries/re-tears expected to be minimized by incorporating biomimicking, stress-reducing features within grafts. At bone-tendon interfaces (entheses), stress can be reduced via angled insertion, geometric flaring, mechanical gradation, and interdigitation of tissues. Here, we incorporated enthesis attributes into 3D in silico and physical models of a unique suture anchor-tendon hybrid graft (SATHG) and investigated their effects on stress reduction via finite element analyses (FEA) studies. Over 20 different simulations altering SATHG angulation, flaring, mechanical gradation, and interdigitation identified an optimal design, which included 90° angulation, 25° flaring, and a compliant (ascending then descending) mechanical gradient in SATHG's bone-to-tendon-like transitional region. This design reduced peak stress concentration factor (SCF) by 43.6 % relative to an ascending-only mechanical gradient typically used in hard-to-soft tissue engineering. To verify FEA results, SATHG models were fabricated using a photocrosslinkable bone-tendon-like polyurethane (QHM polymer) for ex vivo tensile assessment. Tensile testing showed that ultimate load (132.9 N), displacement-at-failure (1.78 mm), stiffness (135.4 N/mm), and total work-to-failure (422.1 × 10-3 J) were highest in the optimized design. Furthermore, to assess envisioned usage, SATHG pull-out testing and 6-week in vivo implantation into large, 0.5-cm segmental supraspinatus tendon defects was performed. SATHG pull-out testing showed secure bone attachment while histological assessment such as hematoxylin and eosin (H&E) together with Safranin-O staining showed biocompatibility including enthesis regeneration. This work demonstrates that engineering biomaterials with FEA-optimized, enthesis-like attributes shows potential for enhancing hard-to-soft tissue repair. STATEMENT OF SIGNIFICANCE: Successful repair of hard-to-soft tissue injuries is challenging due to high stress concentrations within bone-tendon/ligament grafts that mechanically compromise repair strength. While stress-reducing gradient biomaterials have been reported, little-to-no attention has focused on other bone-tendon/ligament interface (enthesis) features. To this end, a unique bone-tendon graft (SATHG) was developed by combining two common orthopaedic devices along with biomimetic incorporation of four enthesis-like features to reduce stress and encourage widespread clinician adoption. Notably, utilizing designs based on natural stress dissipation principles such as anchor insertion angle, geometric flaring, and mechanical gradation reduced stress by 43.6 % in silico, which was confirmed ex vivo, while in vivo studies showed SATHG's ability to support native enthesis regeneration. Thus, SATHG shows promise for hard-to-soft tissue repairs.

Gallium-Based Liquid Metals in Rechargeable Batteries: From Properties to Applications.

Gallium-based (Ga-based) liquid metals have attracted considerable interest due to their low melting points, enabling them to feature both liquid properties and metallic properties at room temperature. In light of this, Ga-based liquid metals also possess excellent deformability, high electrical and thermal conductivity, superior metal affinity, and unique self-limited surface oxide, making them popular functional materials in energy storage. This provides a possibility to construct high-performance rechargeable batteries that are deformable, free of dendrite growth, and so on. This review primarily starts with the property of Ga-based liquid metal, and then focuses on the potential applications in rechargeable batteries by exploiting these advantages, aiming to construct the correlation between properties and structures. The glorious applications contain interface protection, self-healing electrode construction, thermal management, and flexible batteries. Finally, the opportunities and obstacles for the applications of liquid metal in batteries are presented.

Interlayer Biatomic Pair Bridging the van der Waals Gap for 100% Activation of 2D Layered Material.

2D layered materials are regarded as prospective catalyst candidates due to their advantageous atomic exposure ratio. Nevertheless, the predominant population of atoms residing on the basal plane with saturated coordination, exhibit inert behavior, while a mere fraction of atoms located at the periphery display reactivity. Here, a novel approach is reported to attain complete atom activation in 2D layered materials through the construction of an interlayer biatomic pair bridge. The atoms in question have been strategically optimized to achieve a highly favorable state for the adsorption of intermediates. This optimization results from the introduction of new gap states around the Fermi level. Moreover, the presence of the interlayer bridge facilitates the electron transfer across the van der Waals gap, thereby enhancing the reaction kinetics. The hydrogen evolution reaction exhibits an impressive ultrahigh current density of 2000 mA cm-2 at 397 mV, surpassing the pristine MoS2 by approximately two orders of magnitude (26 mA cm-2 at 397 mV). This study provides new insights for enhancing the efficacy of 2D layered catalysts.

Quantification of MRI Artifacts in Carbon Fiber Reinforced Polyetheretherketone Thoracolumbar Pedicle Screw Constructs prior to Spinal Stereotactic Radiosurgery.

PURPOSE: Carbon fiber reinforced polyetheretherketone (CFRP) is a nonmetallic material that is a subject of growing interest in the field of spinal instrumentation manufacturing. The radiolucency and low magnetic susceptibility of CFRP has potential to create less interference with diagnostic imaging compared with titanium implants. However, an objective comparison of the image artifact produced by titanium and CFRP implants has not been described. Spinal oncology, particularly after resection of spinal tumors and at the time of spinal stereotactic radiosurgery planning, relies heavily on imaging interpretation for evaluating resection, adjuvant treatment planning, and surveillance. We present a study comparing measurements of postoperative magnetic resonance imaging artifacts between titanium and CFRP pedicle screw constructs in the setting of separation surgery for metastatic disease. METHODS AND MATERIALS: The diameter of the signal drop around the screws (pedicle screw artifact) and the diameter of the spinal canal free from artifacts (canal visualization) were measured in consecutive patients who had spinal instrumentation followed by spinal stereotactic radiosurgery in the June 2019 to May 2022 timeframe. The spinal cord presented a shift at the screw level in sagittal images which was also measured (Sagittal Distortion, SagD). RESULTS: Fifty patients, corresponding to 356 screws and 183 vertebral levels, were evaluated overall. CFRP produced less artifacts in all the 3 parameters compared with titanium: mean pedicle screw artifact (CFRP = 5.8 mm, Ti = 13.2 mm), canal visualization (CFRP = 19.2 mm, Ti = 15.5 mm), and SagD (CFRP = .5 mm, Ti = 1.9 mm), all P < .001. In practice, these findings translate into better-quality magnetic resonance imaging. CONCLUSIONS: The initial perceived advantages are easier evaluation of postoperative imaging, facilitating radiation treatment planning, recurrence detection, and avoidance in repeating a suboptimal computed tomography myelogram. Further clinical studies analyzing long-term outcomes of patients treated with CFRP implants are necessary.

Neutrophil extracellular traps aggravate intestinal epithelial necroptosis in ischaemia-reperfusion by regulating TLR4/RIPK3/FUNDC1-required mitophagy.

Neutrophil extracellular trap (NET) has been confirmed to be related to gut barrier injury during intestinal ischaemia-reperfusion (II/R). However, the specific molecular regulatory mechanism of NETs in II/R-induced intestinal barrier damage has yet to be fully elucidated. Here, we reported increased NETs infiltration accompanied by elevated inflammatory cytokines, cellular necroptosis and tight junction disruption in the intestine of human II/R patients. Meanwhile, NETs aggravated Caco-2 intestinal epithelial cell necroptosis, impairing the monolayer barrier in vitro. Moreover, Pad4-deficient mice were used further to validate the role of NETs in II/R-induced intestinal injury. In contrast, NET inhibition via Pad4 deficiency alleviated intestinal inflammation, attenuated cellular necroptosis, improved intestinal permeability, and enhanced tight junction protein expression. Notably, NETs prevented FUN14 domain-containing 1 (FUNDC1)-required mitophagy activation in intestinal epithelial cells, and stimulating mitophagy attenuated NET-associated mitochondrial dysfunction, cellular necroptosis, and intestinal damage. Mechanistically, silencing Toll-like receptor 4 (TLR4) or receptor-interacting protein kinase 3 (RIPK3) via shRNA relieved mitophagy limitation, restored mitochondrial function and reduced NET-induced necroptosis in Caco-2 cells, whereas this protective effect was reversed by TLR4 or RIPK3 overexpression. The regulation of TLR4/RIPK3/FUNDC1-required mitophagy by NETs can potentially induce intestinal epithelium necroptosis.

Interleukin-4 and Interleukin-17 are associated with coronary artery disease.

INTRODUCTION: The present study aimed to examine the correlation between serum cytokine levels and the incidence of coronary artery disease (CAD), a leading cause of mortality globally, which is known to have a strong association with inflammatory factors. The study further sought to determine the predictors of CAD to distinguish patients with coronary artery lesions from those suspected of having CAD. METHODS AND RESULTS: In this study, 487 patients who underwent coronary angiography as a result of suspected CAD but without acute myocardial infarction (AMI) were recruited. The serum levels of the cytokines interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α, interferon (IFN)-α, and IFN-γ were measured using a multiplexed particle-based flow cytometric assay technique. The results of the study revealed that the levels of IL-4, IL-12p70, IL-17, IFN-α, and IFN-γ in the CAD group were significantly lower compared to those in the non-CAD group. Multivariate logistic regression analysis indicated that two serum cytokines (IL-4 and IL-17), one protective factor (high-density lipoprotein cholesterol [HDL-C]), and three risk factors (sex, smoking, and diabetes) were independently predictive of CAD. The receiver operating characteristic curve analysis showed that the combined use of these predictors in a multivariate model demonstrated good predictive performance for CAD, as evidenced by an area under the curve value of 0.826. CONCLUSION: The results of the study indicated that serum IL-4 and IL-17 levels serve as independent predictors of CAD. The risk prediction model established in the research, which integrates these serum cytokines (IL-4 and IL-17) with relevant clinical risk factors (gender, smoking, and diabetes) and the protective factor HDL-C, holds the potential to differentiate patients with CAD from those suspected of having CAD but without AMI.